- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01777542
Treatment of Rett Syndrome With Recombinant Human IGF-1
Pharmacological Treatment of Rett Syndrome by Stimulation of Synaptic Maturation With Recombinant Human IGF-1(Mecasermin [rDNA] Injection)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Enrolled subjects will complete five study periods: screening, two 20-week long treatment periods, a 28-week break between treatment periods ("washout"), and a follow-up phone call 4 weeks after all treatment ends. Subjects will be chosen at random to receive either IGF-1 or placebo during the first treatment period and then switch to the alternate medication for the second treatment period. Therefore, by completion of the trial, all subjects will have received treatment with IGF-1 for 20 weeks. The study will be double-blinded; meaning, neither subjects' families nor study investigators will know who is receiving IGF-1 or placebo at any time. Treatment must be administered by the caregiver twice daily through subcutaneous (just underneath the skin) injections. Caregivers will be trained by research nurses in how to administer the medication. Participation in this study will last approximately eighteen months.
Throughout the course of the trial, investigators will collect information to assess the effects of IGF-1 and monitor for safety. Families must attend study visits at Boston Children's Hospital a total of seven times (including the screening visit) over the course of 18 months. These visits cannot be completed at any other hospital. Parents will fill out questionnaires and undergo a structured interview reporting on their child's health, behavior, and mood. Subjects will undergo clinical and physical examinations by a study doctor. Non-invasive devices and cameras will also be used to monitor things like breathing, hand movements, heart rate, and body temperature. Blood and urine will be collected for routine laboratory tests to monitor for safety. Investigators will also monitor safety by asking parents to complete a medication diary and side effect reporting form on a regular basis. Between trips to Boston Children's Hospital, parents will complete a set of online questionnaires and undergo a structured interview over the phone.
The cost of travel and lodging during research-related visits to and from the hospital will not be covered by the study. If a condition or illness is identified during the trial (and is determined to be unrelated to study treatments), referrals to outside medical care will be made. Study medications and all research-related materials and services will be provided at no cost to participants. Parking vouchers will be provided for all study-related hospital visits.
The study is investigating 5 potential effects:
- IGF-1 may improve subjects' behavior, communication and/or mood. In order to measure this, investigators will evaluate subjects every 5 weeks throughout each treatment period with behavioral and psychological assessments. All of the tests used during these evaluations are non-invasive. Investigators will ask parents what their impressions are about their child's behavior and day-to-day activities through a structured parental interview and various questionnaires.
- Investigators will examine subjects' brain function through use of a brain- monitoring device known as electroencephalography (EEG). The EEG measurements will be taken while investigators present subjects with exercises to stimulate their vision and hearing. EEG is a non-invasive way of recording the electrical activity of a subject's brain by applying a net of monitors (electrodes) to their scalp. Through this method investigators gain insight into how brain processes visual and auditory stimulus.
- As one of the features of RTT is unstable vital signs, investigators are trying to determine if IGF-1 has any effect on normalizing subjects' heart rate and breathing patterns. To measure this, investigators will ask subjects to wear a non-invasive device that includes three electrocardiogram connectors and two stretchy bands that wrap around her chest and abdomen to measure heart rate and respiratory patterns.
- The safety of IGF-1 in children with RTT is very important. Investigators will ask parents to complete a medication diary and side effect reporting form on a regular basis. In addition, laboratory tests will be performed every 10 weeks throughout each treatment period to evaluate the safety of IGF-1. These will be blood tests similar to those provided in typical clinical care. Subjects will undergo regular non-invasive comprehensive physical and neurological examinations, tonsil evaluation, electrocardiogram (ECG), echocardiogram, scoliosis x-ray, bone age x-ray, ophthalmological exam, and measurements of height, weight and head circumference.
- Children with RTT often experience unintended, stereotyped hand movements. The Qsensor® is a non-invasive device worn on a fabric bracelet that continually measures subjects' movement. Investigators will use the Qsensor® to determine whether or not IGF-1 affects the presentation of stereotyped hand movements. As such, investigators will ask subjects to wear the Qsensor® during study visits every 10 weeks throughout each treatment period and occasionally at home.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Boston Children's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of "classic" (or "typical") Rett Syndrome
- Genetic documentation of MECP2 mutation
- Subject must be post-regression (Hagberg Stage 2)
- Subject and caregiver's primary language must be English
- Subject must reside in North America (US and Canada)
- Caregiver must have internet access and be able to complete questionnaires online and communicate via email
- Subject is stable on current medications for at least 4 weeks
- Subject's regimen of non-pharmacological interventions (physical therapy, speech therapy, etc.) is stable for at least 90 days
Exclusion Criteria:
- Severe scoliosis (curvature >40 degrees)
- Bone-age greater than 11 years
- Cardiomegaly (enlarged heart)
- Tanner stage 2 or higher breast development
- Allergy to IGF-1
- Prior use of IGF-1, growth hormone, or sex steroids
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment Period 1
One half of subjects will be randomly assigned to receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1) , and the other half of subjects will be randomly assigned to receive placebo.
|
Subjects will receive twice daily subcutaneous injections of IGF-1.
Other Names:
Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).
Other Names:
|
Placebo Comparator: Treatment Period 2
Subjects that initially received Recombinant Human Insulin Growth Factor 1 (rhIGF-1) will now receive placebo, and subjects that initially received placebo will now receive Recombinant Human Insulin Growth Factor 1 (rhIGF-1).
|
Subjects will receive twice daily subcutaneous injections of IGF-1.
Other Names:
Subjects will receive twice daily subcutaneous injections of a saline solution (placebo).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rett Syndrome Behavior Questionnaire (RSBQ) - Fear/Anxiety Subscale
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The RSBQ is an informant/parent-completed measure of abnormal behaviors typically observed in individuals with RTT, which is completed by a parent/caregiver/LAR. Each item, grouped into eight domains/factors: General mood, Breathing problems, Body rocking and expressionless face, Hand behaviors, Repetitive face movements, Night-time behaviors, Fear/anxiety and Walking/standing), is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true." The total sum of items in each subscale is reported. For the fear/anxiety subscale, the sum total could be between 0-8. The higher the sum total score, the greater the frequency of fear/anxiety behaviors. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Anxiety, Depression, and Mood Scale (ADAMS) - Social Avoidance Subscale
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The ADAMS is completed by the parent/caregiver/LAR and consists of 29 items which are scored on a 4-point rating scale that combines frequency and severity ratings. The instructions ask the rater to describe the individual's behavior over the last six months on the following scale: "0" if the behavior has not occurred, "1" if the behavior occurs occasionally or is a mild problem, "2" if the behavior occurs quite often or is moderate problem, or "3" if the behavior occurs a lot or is a severe problem. The Social Avoidance subscale of the ADAMS will be used as a primary outcome measure for this trial. The range for this subscale is 0-21. The higher the subscale score, the more problematic the behavior. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Clinical Global Impression - Severity (CGI-S)
Time Frame: Every 10 weeks during each of the two 20-week treatment periods
|
This scale is used to judge the severity of the subject's disease prior to entry into the study. The clinician will rate the severity of behavioral symptoms at baseline on a 7-point scale from not impaired to the most impaired. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7. |
Every 10 weeks during each of the two 20-week treatment periods
|
Clinical Global Impression - Improvement (CGI-I)
Time Frame: Every 10 weeks during each of the two 20-week treatment periods
|
Each time the patient was seen after the study intervention was initiated, the clinician compared the patient's overall clinical condition to the CGI-S score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7. |
Every 10 weeks during each of the two 20-week treatment periods
|
Parental Global Impression - Severity (PGI-S)
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The PGI-S is the parent version of the CGI-S. Parents/caregivers/LAR are asked to rate the severity of their child's symptoms at baseline on a 7-point scale from not at all impaired to the most impaired. The parents/caregivers/LAR will complete the PGI-S at each study visit. The scores that correspond to each possible grouping are as follows: 1=Normal, not at all impaired; 2=Borderline impaired; 3=Mildly impaired; 4=Moderately impaired; 5=Markedly impaired; 6=Severely impaired; 7=The most impaired. The possible range for reported scores is 1-7. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Parental Global Impression - Improvement (PGI-I)
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
As part of each visit after the study intervention was initiated, the parent/caregiver was asked to compare the patient's overall clinical condition to the score obtained at the baseline (visit 1) visit. Based on information collected, the clinician determined if any improvement occurred on the following 7-point scale: 1=Very much improved since the initiation of treatment; 2=Much improved; 3=Minimally improved; 4=No change from baseline (the initiation of treatment); 5=Minimally worse; 6=Much worse; 7=Very much worse since the initiation of treatment. The possible range for reported scores is 1-7. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 1
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 2
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Parent Targeted Visual Analog Scale (PTSVAS) - Scale 3
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The parent or caretaker identifies the three most troublesome, RTT-specific, "target" symptoms, such as inattention or breath-holding. This allows the problems that are of concern to parents and the family to be targeted in the trial. In this study the caregiver will choose three target symptoms at baseline and then rate changes in severity of each target symptom on a visual analog scale (VAS). The VAS is a 10 cm line, where a target symptom is anchored on one end with the description "the best it has ever been" and on the other with the description "the worst it has ever been." The parent was asked to marked on the line where they felt their child's symptoms currently fit best. This mark was measured as recorded as a numeric value from 0.00-10.00 cm. The higher the value, the worse the symptom. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Kerr Clinical Severity Scale
Time Frame: At the start and end of each 20-week treatment period
|
The Kerr clinical severity scale (Kerr scale) is a quantitative measure of global disease severity. The Kerr scale is a summation of individual items related to Rett syndrome phenotypic characteristics. The items are based on the severity or degree of abnormality of each characteristic on a discrete scale (0, 1, 2) with the highest level corresponding to the most severe or most abnormal presentations. The possible range of scores is 0-48. The higher the score, the more severe the symptoms. |
At the start and end of each 20-week treatment period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rett Syndrome Behavior Questionnaire (RSBQ)
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The RSBQ is a parent-completed measure of abnormal behaviors typically observed in individuals with RTT. Each item, grouped into eight subscales, is scored on a Likert scale of 0-2, according to how well the item describes the individual's behavior. A score of "0" indicates the described item is "not true," a score of "1" indicates the described item is "somewhat or sometimes true," and a score of "2" indicates the described item is "very true or often true." The total sum of each subscale is reported. The higher the score, the more severe the symptoms of that subscale in the participant. The range for each subscale is as follows: General Mood: 0-16 Body rocking and expressionless face: 0-14 Hand behaviors: 0-12 Breathing Problems: 0-10 Repetitive Face Movements: 0-8 Night-time behaviors: 0-6 Walking Standing: 0-4 The fear/anxiety subscale was used as a primary outcome measure in this study and results can be found in that section. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Anxiety, Depression, and Mood Scale (ADAMS)
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Remaining subscales of the ADAMS that are not primary outcome measures include: Manic/hyperactive, Depressed mood, General anxiety, Obsessive/compulsive behavior. The range for each subscale is as follows: Manic/Hyperactive Behavior: 0-15 Depressed Mood: 0-21 General Anxiety: 0-21 Obsessive/Compulsive Behavior: 0-9 The higher the score for each subscale, the more problematic the behavior. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Mullen Scales of Early Learning (MSEL)
Time Frame: At the start and end of each 20-week treatment period
|
The MSEL is a standardized developmental test for children ages 3 to 68 months consisting of five subscales: gross motor, fine motor, visual reception, expressive language, and receptive language. The raw score is reported for each subscale domain. The potential score ranges are as follows: Visual Reception: 33 items, score range=0-50, Fine Motor: 30 items, score range= 0-49, Receptive Language: 33 items, score range= 0-48, Expressive Language: 28 items, score range= 0-50. The gross motor subscale was not included in this population. A higher raw score indicates more advanced abilities in that section. |
At the start and end of each 20-week treatment period
|
Vineland Adaptive Behavior Scales, Second Edition (VABS-II)
Time Frame: At the start and end of each 20-week treatment period
|
The VABS-II is a survey designed to assess personal and social functioning. Within each domain (Communication, Daily Living Skills, Socialization, and Motor Skills), items can given a score of "2" if the participant successfully performs the activity usually; a "1" if the participant successfully performs the activity sometimes, or needs reminders; a "0" if the participant never performs the activity, and a "DK" if the parent/caregiver is unsure of the participant's ability for an item. The raw scores in each sub-domain are reported and the ranges for these are as follows: [Communication Domain], Receptive Language=0-40, Expressive Language=0-108, Written Language=0-50; [Daily Living Skills Domain], Personal=0-82, Domestic=0-48, Community=0-88; [Socialization Domain], Interpersonal Relationships=0-76, Play and Leisure Time=0-62, Coping Skills=0-60; [Motor Skills Domain]: Gross Motor Skills=0-80, Fine Motor Skills=0-72. A higher score indicates more advanced abilities. |
At the start and end of each 20-week treatment period
|
Communication and Symbolic Behavior Scales - Developmental Profile (CSBS-DP)
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The CSBS-DP was designed to measure early communication and symbolic skills in infants and young children (that is, functional communication skills of 6 month to 2 year olds). The CSBS-DP measures skills from three composites: (a) Social (emotion, eye gaze, and communication); (b) Speech (sounds and words); and (c) Symbolic (understanding and object use) and asks about developmental milestones. The data reported are the composite scores for these three categories. The possible scores for the three composite categories are as follows: Social Composite = 0-48; Speech Composite = 0-40; Symbolic Composite = 0-51. A higher score indicates more advanced abilities in that area. |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Aberrant Behavior Checklist - Community Edition (ABC-C)
Time Frame: Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
The ABC-C is a global behavior checklist implemented for the measurement of drug and other treatment effects in populations with intellectual disability. Behavior based on 58 items that describe various behavioral problems. Each item is rated on the parents perceived severity of the behavior. The answer options for each item are: 0 = Not a problem
The measure is broken down into the following subscales with individual ranges as follows: Subscale I (Irritability): 15 items, score range = 0-45 Subscale II (Lethargy): 16 items, score range = 0-48 Subscale III (Stereotypy): 7 items, score range = 0-21 Subscale IV (Hyperactivity): 16 items, score range = 0-48 Subscale V (Inappropriate Speech) was not included in the breakdown because it was not applicable (no participants in the study had verbal language). |
Every 5 weeks during each of the two 20-week treatment periods, and once 4 weeks after final treatment ends
|
Quantitative Measures of Respiration: Apnea Index
Time Frame: Every 10 weeks during each of the two 20-week treatment periods
|
Respiratory data was collected using non-invasive respiratory inductance plethysmography from a BioCapture® recording device. BioCapture® is a child-friendly measurement device that can record from 1 to 12 physiological signal transducers in a time-locked manner. It can be configured with the pediatric chest and abdominal plethysmography bands and the 3 lead ECG signals we plan to use for monitoring cardiac safety throughout the study. Each transducer is placed on the patient independently to provide a customized fit that yields the highest signal quality for each patient irrespective of body shape and proportion. The transducer signals captured by the BioCapture® are transmitted wirelessly to a laptop computer where all signals are displayed in real-time. The apnea index is given as apneas/hour. Data on apneas greater than or equal to 10 seconds are displayed below. The higher the frequency of apnea, the more severe the breathing abnormality. |
Every 10 weeks during each of the two 20-week treatment periods
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Khwaja OS, Ho E, Barnes KV, O'Leary HM, Pereira LM, Finkelstein Y, Nelson CA 3rd, Vogel-Farley V, DeGregorio G, Holm IA, Khatwa U, Kapur K, Alexander ME, Finnegan DM, Cantwell NG, Walco AC, Rappaport L, Gregas M, Fichorova RN, Shannon MW, Sur M, Kaufmann WE. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4596-601. doi: 10.1073/pnas.1311141111. Epub 2014 Mar 12.
- Chao HT, Zoghbi HY, Rosenmund C. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron. 2007 Oct 4;56(1):58-65. doi: 10.1016/j.neuron.2007.08.018.
- Bebbington A, Anderson A, Ravine D, Fyfe S, Pineda M, de Klerk N, Ben-Zeev B, Yatawara N, Percy A, Kaufmann WE, Leonard H. Investigating genotype-phenotype relationships in Rett syndrome using an international data set. Neurology. 2008 Mar 11;70(11):868-75. doi: 10.1212/01.wnl.0000304752.50773.ec.
- Schultz RJ, Glaze DG, Motil KJ, Armstrong DD, del Junco DJ, Hubbard CR, Percy AK. The pattern of growth failure in Rett syndrome. Am J Dis Child. 1993 Jun;147(6):633-7. doi: 10.1001/archpedi.1993.02160300039018.
- Williamson SL, Christodoulou J. Rett syndrome: new clinical and molecular insights. Eur J Hum Genet. 2006 Aug;14(8):896-903. doi: 10.1038/sj.ejhg.5201580.
- Weese-Mayer DE, Lieske SP, Boothby CM, Kenny AS, Bennett HL, Silvestri JM, Ramirez JM. Autonomic nervous system dysregulation: breathing and heart rate perturbation during wakefulness in young girls with Rett syndrome. Pediatr Res. 2006 Oct;60(4):443-9. doi: 10.1203/01.pdr.0000238302.84552.d0. Epub 2006 Aug 28.
- Percy AK. Clinical trials and treatment prospects. Ment Retard Dev Disabil Res Rev. 2002;8(2):106-11. doi: 10.1002/mrdd.10022.
- Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999 Oct;23(2):185-8. doi: 10.1038/13810.
- Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature. 1998 May 28;393(6683):386-9. doi: 10.1038/30764.
- Shahbazian MD, Antalffy B, Armstrong DL, Zoghbi HY. Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet. 2002 Jan 15;11(2):115-24. doi: 10.1093/hmg/11.2.115.
- Cohen DR, Matarazzo V, Palmer AM, Tu Y, Jeon OH, Pevsner J, Ronnett GV. Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol Cell Neurosci. 2003 Apr;22(4):417-29. doi: 10.1016/s1044-7431(03)00026-5.
- Gemelli T, Berton O, Nelson ED, Perrotti LI, Jaenisch R, Monteggia LM. Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol Psychiatry. 2006 Mar 1;59(5):468-76. doi: 10.1016/j.biopsych.2005.07.025. Epub 2005 Sep 30.
- Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet. 2001 Mar;27(3):322-6. doi: 10.1038/85899.
- Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron. 2002 Jul 18;35(2):243-54. doi: 10.1016/s0896-6273(02)00768-7.
- Giacometti E, Luikenhuis S, Beard C, Jaenisch R. Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1931-6. doi: 10.1073/pnas.0610593104. Epub 2007 Jan 31.
- Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB. Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12560-5. doi: 10.1073/pnas.0506071102. Epub 2005 Aug 22.
- Nelson ED, Kavalali ET, Monteggia LM. MeCP2-dependent transcriptional repression regulates excitatory neurotransmission. Curr Biol. 2006 Apr 4;16(7):710-6. doi: 10.1016/j.cub.2006.02.062.
- Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron. 2006 Feb 2;49(3):341-8. doi: 10.1016/j.neuron.2005.12.027.
- Schuman EM. Neurotrophin regulation of synaptic transmission. Curr Opin Neurobiol. 1999 Feb;9(1):105-9. doi: 10.1016/s0959-4388(99)80013-0.
- Bondy CA. Transient IGF-I gene expression during the maturation of functionally related central projection neurons. J Neurosci. 1991 Nov;11(11):3442-55. doi: 10.1523/JNEUROSCI.11-11-03442.1991.
- Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell. 1993 Oct 8;75(1):59-72.
- Tropea D, Kreiman G, Lyckman A, Mukherjee S, Yu H, Horng S, Sur M. Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex. Nat Neurosci. 2006 May;9(5):660-8. doi: 10.1038/nn1689. Epub 2006 Apr 23.
- Yoshii A, Constantine-Paton M. BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation. Nat Neurosci. 2007 Jun;10(6):702-11. doi: 10.1038/nn1903. Epub 2007 May 21.
- Zheng WH, Quirion R. Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival. J Neurochem. 2004 May;89(4):844-52. doi: 10.1111/j.1471-4159.2004.02350.x.
- Ramsey MM, Adams MM, Ariwodola OJ, Sonntag WE, Weiner JL. Functional characterization of des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampus. J Neurophysiol. 2005 Jul;94(1):247-54. doi: 10.1152/jn.00768.2004.
- Xing C, Yin Y, Chang R, Gong X, He X, Xie Z. Effects of insulin-like growth factor 1 on synaptic excitability in cultured rat hippocampal neurons. Exp Neurol. 2007 May;205(1):222-9. doi: 10.1016/j.expneurol.2007.01.029. Epub 2007 Feb 7.
- Riikonen R, Makkonen I, Vanhala R, Turpeinen U, Kuikka J, Kokki H. Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism. Dev Med Child Neurol. 2006 Sep;48(9):751-5. doi: 10.1017/S0012162206001605.
- Acampa M, Guideri F. Cardiac disease and Rett syndrome. Arch Dis Child. 2006 May;91(5):440-3. doi: 10.1136/adc.2005.090290.
- Johnston MV, Jeon OH, Pevsner J, Blue ME, Naidu S. Neurobiology of Rett syndrome: a genetic disorder of synapse development. Brain Dev. 2001 Dec;23 Suppl 1:S206-13. doi: 10.1016/s0387-7604(01)00351-5.
- Kaufmann WE, Taylor CV, Hohmann CF, Sanwal IB, Naidu S. Abnormalities in neuronal maturation in Rett syndrome neocortex: preliminary molecular correlates. Eur Child Adolesc Psychiatry. 1997;6 Suppl 1:75-7. Erratum In: Eur Child Adolesc Psychiatry 1998 Jun;7(2):124.
- Kaufmann WE, MacDonald SM, Altamura CR. Dendritic cytoskeletal protein expression in mental retardation: an immunohistochemical study of the neocortex in Rett syndrome. Cereb Cortex. 2000 Oct;10(10):992-1004. doi: 10.1093/cercor/10.10.992.
- Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C, Fu DD, Flannery R, Jaenisch R, Sur M. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):2029-34. doi: 10.1073/pnas.0812394106.
- Julu PO, Kerr AM, Apartopoulos F, Al-Rawas S, Engerstrom IW, Engerstrom L, Jamal GA, Hansen S. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child. 2001 Jul;85(1):29-37. doi: 10.1136/adc.85.1.29.
- Chen RZ, Akbarian S, Tudor M, Jaenisch R. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet. 2001 Mar;27(3):327-31. doi: 10.1038/85906.
- Castro J, Garcia RI, Kwok S, Banerjee A, Petravicz J, Woodson J, Mellios N, Tropea D, Sur M. Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome. Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9941-6. doi: 10.1073/pnas.1311685111. Epub 2014 Jun 23.
- Pini G, Scusa MF, Congiu L, Benincasa A, Morescalchi P, Bottiglioni I, Di Marco P, Borelli P, Bonuccelli U, Della-Chiesa A, Prina-Mello A, Tropea D. IGF1 as a Potential Treatment for Rett Syndrome: Safety Assessment in Six Rett Patients. Autism Res Treat. 2012;2012:679801. doi: 10.1155/2012/679801. Epub 2012 Jun 13.
- Lopez-Lopez C, LeRoith D, Torres-Aleman I. Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9833-8. doi: 10.1073/pnas.0400337101. Epub 2004 Jun 21.
- Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci. 2000 Apr 15;20(8):2896-903. doi: 10.1523/JNEUROSCI.20-08-02896.2000.
- Pan W, Kastin AJ. Interactions of IGF-1 with the blood-brain barrier in vivo and in situ. Neuroendocrinology. 2000 Sep;72(3):171-8. doi: 10.1159/000054584.
- Kaufmann WE, Tierney E, Rohde CA, Suarez-Pedraza MC, Clarke MA, Salorio CF, Bibat G, Bukelis I, Naram D, Lanham DC, Naidu S. Social impairments in Rett syndrome: characteristics and relationship with clinical severity. J Intellect Disabil Res. 2012 Mar;56(3):233-47. doi: 10.1111/j.1365-2788.2011.01404.x. Epub 2011 Mar 8.
- Mount RH, Charman T, Hastings RP, Reilly S, Cass H. The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. J Child Psychol Psychiatry. 2002 Nov;43(8):1099-110. doi: 10.1111/1469-7610.00236.
- Esbensen AJ, Rojahn J, Aman MG, Ruedrich S. Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. J Autism Dev Disord. 2003 Dec;33(6):617-29. doi: 10.1023/b:jadd.0000005999.27178.55.
- Rojahn J, Rowe EW, Kasdan S, Moore L, van Ingen DJ. Psychometric properties of the Aberrant Behavior Checklist, the Anxiety, Depression and Mood Scale, the Assessment of Dual Diagnosis and the Social Performance Survey Schedule in adults with intellectual disabilities. Res Dev Disabil. 2011 Nov-Dec;32(6):2309-20. doi: 10.1016/j.ridd.2011.07.035. Epub 2011 Sep 1.
- Barnes KV, Coughlin FR, O'Leary HM, Bruck N, Bazin GA, Beinecke EB, Walco AC, Cantwell NG, Kaufmann WE. Anxiety-like behavior in Rett syndrome: characteristics and assessment by anxiety scales. J Neurodev Disord. 2015;7(1):30. doi: 10.1186/s11689-015-9127-4. Epub 2015 Sep 15.
- Hagberg B. Clinical manifestations and stages of Rett syndrome. Ment Retard Dev Disabil Res Rev. 2002;8(2):61-5. doi: 10.1002/mrdd.10020.
- McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002 Aug 1;347(5):314-21. doi: 10.1056/NEJMoa013171.
- Arnold LE, Vitiello B, McDougle C, Scahill L, Shah B, Gonzalez NM, Chuang S, Davies M, Hollway J, Aman MG, Cronin P, Koenig K, Kohn AE, McMahon DJ, Tierney E. Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials. J Am Acad Child Adolesc Psychiatry. 2003 Dec;42(12):1443-50. doi: 10.1097/00004583-200312000-00011.
- Arnold LE, Wender PH, McCloskey K, Snyder SH. Levoamphetamine and dextroamphetamine: comparative efficacy in the hyperkinetic syndrome. Assessment by target symptoms. Arch Gen Psychiatry. 1972 Dec;27(6):816-22. doi: 10.1001/archpsyc.1972.01750300078015. No abstract available.
- Arnold LE, Christopher J, Huestis R, Smeltzer DJ. Methylphenidate vs dextroamphetamine vs caffeine in minimal brain dysfunction: controlled comparison by placebo washout design with Bayes' analysis. Arch Gen Psychiatry. 1978 Apr;35(4):463-73. doi: 10.1001/archpsyc.1978.01770280073008.
- Arnold LE, Huestis RD, Smeltzer DJ, Scheib J, Wemmer D, Colner G. Levoamphetamine vs dextroamphetamine in minimal brain dysfunction. Replication, time response, and differential effect by diagnostic group and family rating. Arch Gen Psychiatry. 1976 Mar;33(3):292-301. doi: 10.1001/archpsyc.1976.01770030012002.
- Fidler DJ, Hepburn S, Rogers S. Early learning and adaptive behaviour in toddlers with Down syndrome: evidence for an emerging behavioural phenotype? Downs Syndr Res Pract. 2006 Jun;9(3):37-44. doi: 10.3104/reports.297.
- Mirrett PL, Bailey DB Jr, Roberts JE, Hatton DD. Developmental screening and detection of developmental delays in infants and toddlers with fragile X syndrome. J Dev Behav Pediatr. 2004 Feb;25(1):21-7. doi: 10.1097/00004703-200402000-00004.
- Carter AS, Volkmar FR, Sparrow SS, Wang JJ, Lord C, Dawson G, Fombonne E, Loveland K, Mesibov G, Schopler E. The Vineland Adaptive Behavior Scales: supplementary norms for individuals with autism. J Autism Dev Disord. 1998 Aug;28(4):287-302. doi: 10.1023/a:1026056518470.
- Berry-Kravis E, Krause SE, Block SS, Guter S, Wuu J, Leurgans S, Decle P, Potanos K, Cook E, Salt J, Maino D, Weinberg D, Lara R, Jardini T, Cogswell J, Johnson SA, Hagerman R. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol. 2006 Oct;16(5):525-40. doi: 10.1089/cap.2006.16.525.
- Wetherby AM, Allen L, Cleary J, Kublin K, Goldstein H. Validity and reliability of the communication and symbolic behavior scales developmental profile with very young children. J Speech Lang Hear Res. 2002 Dec;45(6):1202-18. doi: 10.1044/1092-4388(2002/097).
- Picard RW. Future affective technology for autism and emotion communication. Philos Trans R Soc Lond B Biol Sci. 2009 Dec 12;364(1535):3575-84. doi: 10.1098/rstb.2009.0143.
- Poh MZ, Swenson NC, Picard RW. A wearable sensor for unobtrusive, long-term assessment of electrodermal activity. IEEE Trans Biomed Eng. 2010 May;57(5):1243-52. doi: 10.1109/TBME.2009.2038487. Epub 2010 Feb 17.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Syndrome
- Rett Syndrome
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Mitosis Modulators
- Growth Substances
- Insulin
- Insulin, Globin Zinc
- Mitogens
- Mecasermin
Other Study ID Numbers
- IRB-P00005610
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rett Syndrome
-
University of Alabama at BirminghamUniversity of Colorado, Denver; Eunice Kennedy Shriver National Institute of... and other collaboratorsCompletedRett Syndrome, Preserved Speech Variant | Mecp2 Duplication Syndrome | Rett-related DisordersUnited States
-
Children's Hospital of PhiladelphiaNational Institute of Neurological Disorders and Stroke (NINDS); Vanderbilt...RecruitingRett Syndrome | Rett Syndrome, Atypical | RTTUnited States
-
University of Alabama at BirminghamUniversity of Colorado, Denver; Eunice Kennedy Shriver National Institute of... and other collaboratorsCompletedRett Syndrome | MECP2 Duplication Disorder | Rett-related DisorderUnited States
-
International Rett Syndrome FoundationBaylor College of Medicine; Children's Hospital of Philadelphia; University of... and other collaboratorsRecruitingNervous System Diseases | Neurologic Manifestations | Neurobehavioral Manifestations | Genetic Diseases, X-Linked | Intellectual Disability | Neurodevelopmental Disorders | Neurologic Disorder | Rett Syndrome | Genetic Disease | Rett Syndrome, AtypicalUnited States
-
Assistance Publique - Hôpitaux de ParisCompleted
-
University Hospital, Basel, SwitzerlandNovartisCompletedRett's SyndromeSwitzerland
-
ACADIA Pharmaceuticals Inc.CompletedRett SyndromeUnited States
-
ACADIA Pharmaceuticals Inc.Completed
-
IRCCS Eugenio MedeaAssociazione Italiana Rett (AIRett) O.n.l.u.s.Completed
-
Rett Syndrome Research TrustDuke UniversityCompletedRett SyndromeUnited States
Clinical Trials on Recombinant Human Insulin Growth Factor 1 (rhIGF-1)
-
Massachusetts General HospitalCompletedDisorder of Bone Density and Structure, UnspecifiedUnited States
-
CardioVascular BioTherapeutics, Inc.Not yet recruitingMyocardial Ischemia | Coronary Disease | Coronary Heart Disease | Coronary Arteriosclerosis
-
EMD SeronoTerminatedArthritis, PsoriaticUnited States, Canada
-
Wright State UniversityRecruitingAging | UVB Phototherapy Burn | Insulin-like Growth Factor 1United States
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnMalignant Neoplasm | Gastrointestinal Mucositis
-
Beijing Tongren HospitalRecruiting
-
Martin, PaulNational Cancer Institute (NCI)CompletedPrimary Myelofibrosis | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Chronic Myelomonocytic Leukemia | Recurrent Adult Acute Myeloid Leukemia | Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Adult Burkitt Lymphoma and other conditionsUnited States
-
Dompé Farmaceutici S.p.ACompletedKeratitis | Neurotrophic Keratitis | Corneal UlcerGermany, Italy, France, Poland, Spain, United Kingdom
-
Digna Biotech S.L.Unknown
-
Daewoong Pharmaceutical Co. LTD.CompletedDiabetic Foot Ulcer Patients With Uncontrolled Diabetes MellitusKorea, Republic of