- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04041713
A Pilot Study of an Antioxidant Cocktail vs. Placebo in the Treatment of Children and Adolescents With Rett Syndrome
Study Overview
Detailed Description
There are currently no available medicines shown to be effective for Rett syndrome. Numerous studies implicate mitochondrial dysfunction and oxidative stresses in the pathophysiology of Rett syndrome. Mitochondrial dysfunction has been reported in Rett patients, Rett mouse models and MECP2-deficient cells.
Collaborators have tested a combination of specific antioxidants known to enhance mitochondrial function in a cell and mouse model of Rett syndrome. The formulation normalized mitochondrial membrane potential in MECP2 neurons, and MECP2-deficient mice displayed improved exploratory, locomotor and social behavior compared to MECP2-deficient mice. These results support testing anti-oxidative strategies for benefit in individuals with Rett syndrome.In this study, the formulation has been adjusted and optimized based on current guidelines for human use, with the goal of translating a potential new treatment from the animal model to use in humans. Results of this study could lead to the first approved medication treatment for the disorder.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Rianne Hastie Adams, MSW
- Phone Number: 6515 416 425 6220
- Email: rhastieadams@hollandbloorview.ca
Study Contact Backup
- Name: Naomi Peleg, MSc
- Phone Number: 3469 416 425 6220
- Email: npeleg@hollandbloorview.ca
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M4G 1R8
- Holland Bloorview Kids Rehabilitation Hospital
-
Contact:
- Rianne Hastie Adams, MSW
- Phone Number: 6515 4164256220
- Email: rhastieadams@hollandbloorview.ca
-
Contact:
- Naomi Peleg, MSc
- Phone Number: 6439 4164256220
- Email: npeleg@hollandbloorview.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Female outpatients 2-21 years of age inclusive.
- Diagnosis of Rett syndrome.
- At least partially ambulatory (may need assistive device to take a step).
If already receiving stable interventions must meet the following criteria:
- If already receiving stable concomitant medications or nutraceuticals affecting behaviour, must be on a stable dose during the preceding 1 month prior to Screening (with the exception of fluoxetine, where a period of 6 weeks is needed), and will not electively initiate new or modify ongoing medications for study duration.
- Have normal laboratory test results at Screening/Baseline. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigator.
- Ability to complete assessments, fluency in English (parent/legal guardian; participant, if verbal).
- Ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian(s).
Exclusion Criteria:
- Pregnant females; sexually active females on inadequate birth control (extremely unlikely in this population).
- Have another serious medical condition that, based on Investigator judgment, might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Have evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.).
- Have hypersensitivity to any components of Rett-T.
- Have one or more of the following: HIV, HBV, HCV, hemophilia (bleeding problems, recent nose and brain injuries), drug abuse, immunity disorder, major depressive episode or psychosis.
- Unable to tolerate venipuncture procedures for blood sampling.
- Receiving concomitant medications/nutraceuticals that include any of the components of Rett-T.
- Actively enrolled in another intervention study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Rett T
Rett T is a powder for oral suspension.
Dosage is dependent on weight.
For participants weighing <30 kg, a 4 g dose (i.e., one 4 g sachet) is intended to be administered orally once a day after dissolving in approximately 125 mL of water.
For participants weighing ≥30 kg, a 8 g dose (i.e., two 4 g sachets) is intended to be administered orally once a day after dissolving in approximately 250 mL of water.
|
antioxidant cocktail
|
Placebo Comparator: Placebo
Placebo is a powder for oral suspension.
Dosage is dependent on weight.
For participants weighing <30 kg, a 4 g dose (i.e., one 4 g sachet) is intended to be administered orally once a day after dissolving in approximately 125 mL of water.
For participants weighing ≥30 kg, a 8 g dose (i.e., two 4 g sachets) is intended to be administered orally once a day after dissolving in approximately 250 mL of water.
|
Placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rett Syndrome Natural History Motor Behavior Assessment (MBA)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To examine the effect of Rett-T vs. placebo on measures of motor function.
The Rett Syndrome MBA consists of 37 items grouped into three subscales (Behavioral/Social Assessment, Orofacial Respiratory Assessment, and Motor Assessment/Physical Signs).
Items are captured on a 0-4 point Likert scale.
Total and subscale scores are calculated (subscales are summed for a total score).
The scale range for Total score is 0-136; for Behavioral/Social subscale, 0-60; for Orofacial/Respiratory subscale, 0-28; for Motor Assesment/Physical Signs, 0-48.
For both total and subscale scores, higher values represent a worse outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rett Syndrome Gross Motor Scale (RSGMS)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To examine the effect of Rett-T vs. placebo on measures of motor function.
The RSGMS consists of 15 gross motor items grouped into three subscales (Sitting, Standing and Walking, and Challenge).
Items are captured on a 0-3 Likert Scale rating regarding level of assistance needed (0=maximal, 3 = none).
Total and subscale scores are calculated (subscales are summed for a total score).
The scale range for Total score is 0-45; for Sitting, 0-9; for Walking, 0-27; for Challenge, 0-9.
For both total and subscale scores, higher values represent a better outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
Safety Monitoring Uniform Report Form (SMURF)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To examine the safety and tolerability of Rett- T in children and youth with Rett syndrome; To explore the effect Rett-T vs. placebo on maladaptive behaviors, anxiety, sleep, seizure
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
Clinical Global Impressions - Improvement Scale - Global (CGI-I)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To explore the effect of Rett-T vs. placebo on global improvement.
The CGI-I measures global clinical improvement in response to treatment.
A single score is assigned on a 1-7 Likert scale, with 1= very much improved-7=very much worse.
Higher values represent a worse outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
The Top 3 Causes for Concern
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To explore the effect Rett-T vs. placebo on maladaptive behaviors, anxiety, sleep, seizure frequency, and global improvement.
Respondents are instructed to choose their top three concerns for the participant, and indicate Concern Number #1, 2 and 3 on the form.
Respondents are next instructed to place a vertical mark along a visual analogue scale (a 10 centimetre horizontal line in which the leftmost point on the scale indicates the concern is completely absent, and the rightmost point on the scale indicates that the concern is very severe).
For each concern, a measurement is taken from the leftmost point of the scale to the vertical mark, and the measurement in centimetres acts as the score.
Higher scores represent a worse outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
The Rett Syndrome Behaviour Questionnaire (RSBQ)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To explore the effect of Rett-T vs. placebo on maladaptive behaviors, anxiety, sleep, seizure frequency, and global improvement.
The measure consists of 45 items which are grouped into 8 subscales (General Mood, Breathing Problems, Body Rocking and Expressionless Face, Hand Behaviors, Repetitive Face Movements, Night-time Behaviors, Fear/Anxiety, and Walking/Standing).
Items are measured on a 0-2 Likert scale.Total and subscale scores are calculated (subscales are summed for a total score).
The scale range for total score is 0-90; for General Mood, 0-16; for Breathing Problems, 0-10; for Body Rocking and Expressionless Face, 0-12; for Hand Behaviours, 0-12; for Repetitive Face Movements, 0-8; for Nighttime Behaviours, 0-6; for Fear/Anxiety; 0-8; for Walking/Standing, 0-4.
Seven items are not included in the subscale scores but are included in the total score sum.
For both total and subscale scores, higher values represent a worse outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
Anxiety, Depression, and Mood Scale (ADAMS)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To explore the effect of Rett-T vs. placebo on anxiety.
The ADAMS consists of 28 items grouped into five subscales (Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, and Obsessive Behavior).
Items are scored on a 0-3 Likert scale that combines frequency and severity ratings (where 0=behavior has not occurred or is not a problem, 3=behavior occurs a lot or is a severe problem).
Each subscale score is calculated separately; the scale range for Manic/Hyperactive Behavior is 3-15; for Depressed Mood, 7-21; for Social Avoidance, 7-21; for General Anxiety, 7-21; for Obsessive Behavior, 3-9.
For each subscale score, higher values represent a worse outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
Children's Sleep Habits Questionnaire (CSHQ)
Time Frame: 18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
To explore the effect of Rett-T vs. placebo on sleep.
The CSHQ is a tool designed to screen for the most common sleep problems in children.
The CSHQ consists of 35 items for scoring and extra unscored items intended to provide administrators with other potentially useful information about respondents.
The instrument evaluates sleep based on behavior within eight different subscales (Bedtime Resistance, Sleep-Onset Delay, Sleep Duration, Sleep Anxiety, Night Wakings, Parasomnias, Sleep-Disordered Breathing, and Daytime Sleepiness).Total and subscale scores are calculated (33 items are summed for a total score).
The scale range for Total score is 33-99; for Bedtime Resistance subscale, 6-18; for Sleep Onset/Delay, 1-3; for Sleep Duration, 3-9; for Sleep Anxiety, 4-12; For Night Wakings, 3-9; for Parasomnias, 7-21; for Sleep-Disordered Breathing, 3-9; for Daytime Sleepiness, 8-24.
For both total and subscale scores, higher values represent a worse outcome.
|
18 weeks total: 8 weeks on Rett-T, 8 weeks on placebo, 2 week washout in interim
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Evdokia Anagnostou, MD, Holland Bloorview Kids Rehabilitation Hospital
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
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
Other Study ID Numbers
- RETT-08-2018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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 Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States