- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03633058
A Study to Evaluate Ketamine for the Treatment of Rett Syndrome
March 26, 2024 updated by: Rett Syndrome Research Trust
A Randomized, Double-blind, Placebo-controlled, Cross-over Study to Assess the Safety, Tolerability and Efficacy of Oral Ketamine for Patients With Rett Syndrome
This 2 cohort, sequential, ascending dose study will assess the safety, tolerability and efficacy of oral ketamine dosed in a single 5-day BID regimen in addition to placebo, in a 4-week cross-over design in patients with Rett Syndrome.
Approximately 12 patients per cohort are anticipated to participate for approximately 8-10 weeks at approximately 7 US study centers.
Study Overview
Detailed Description
This study is designed to assess oral ketamine for the treatment of Rett Syndrome and consists of up to 4 ascending dose cohorts, each assessing 1 dose level of ketamine vs placebo.
Patients will receive in either order, a 5-day BID regimen of both placebo and the cohort-specified dose level of oral ketamine.
Patients may only participate in 1 cohort.
Safety and tolerability will be assessed via patient disposition, vital signs, physical examination, adverse events and concomitant medication use.
Efficacy will be assessed via physician and caregiver questionnaires and assessments, and continuous, wearable, at-home biosensor data collection.
An independent safety committee will review safety data from each cohort to determine if the subsequent ascending dose cohort is warranted.
A total of 12 patients per cohort is anticipated at approximately 7 sites.
The screening period will last between 2 and 4 weeks, the cross-over treatment period will last 4 weeks, and the safety follow-up period will last 2 weeks.
Total patient participation is approximately 8-10 weeks.
Study Type
Interventional
Enrollment (Actual)
23
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35294
- University of Alabama Birmingham School of Medicine
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- Rush University Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Boston Children's Hospital
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
-
-
Tennessee
-
Nashville, Tennessee, United States, 37203
- Vanderbilt University Medical Center
-
-
Texas
-
Houston, Texas, United States, 77030
- Texas Children's Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
4 years to 10 years (Child)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Female Rett Syndrome patients diagnosed with Rett Syndrome with a confirmed MECP2 mutation
- between the ages of 6 and 12, inclusive, who have not achieved menarche
- ability to take oral medications
- are generally healthy.
Exclusion Criteria:
- Patients not on stable medication regimens/other types of behavioral, educational, or dietary interventions for at least 4 weeks,
- are taking medications that may interact with ketamine,
- have a condition where increased blood pressure, spinal fluid pressure, or ocular pressure may put the patient at increased risk.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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 |
---|---|
Experimental: 0.75 mg/kg
ketamine will be dosed orally twice daily for 5 days at 0.75 mg/kg, in addition to 5 days of placebo
|
oral ketamine dosed twice daily for 5 days
Other Names:
|
Experimental: 1.5 mg/kg
ketamine will be dosed orally twice daily for 5 days at 0.75 mg/kg, in addition to 5 days of placebo
|
oral ketamine dosed twice daily for 5 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-Limiting Adverse Events
Time Frame: 6 weeks
|
The Number of Participants with Treatment-emergent adverse events on ketamine compared to placebo will be summarized
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Global Impression of Improvement
Time Frame: 4 weeks
|
Clinicians will use a 7 point Likert Scale to rate change from baseline symptom severity by addressing the question, "Compared to the patient's condition of Rett syndrome prior to treatment initiation at baseline, the patient's current condition is: 1 very much improved, 2 much improved, 3 minimally improved, 4 no change, 5 minimally worse, 6 much worse, 7 very much worse.
No change would be scored a 0, while improvement would be scored at -1, -2, or -3 and worsening would be scored +1, +2 or +3, depending on the degree of perceived change.
Negative change indicates improvement while positive change indicates worsening
|
4 weeks
|
Motor Behavioral Assessment
Time Frame: 4 weeks
|
a 37-item questionnaire for clinicians to evaluate current behavioral/social, orofacial/respiratory, and motor/physical symptoms.
Each item is rated either 0 (normal or never), 1 (mild or rare), 2 (moderate or occasional), 3 (marked or frequent), 4 (very severe or constant), where higher numbers indicate higher severity.
Each subscale is summed for a subscale score, while the total score is a sum of the subscale scores.
The behavioral/social subscale score may range from 0 to 64; the orofacial/respiratory subscale may range from 0 to 28, and motor/physical subscale may range from 0 to 56.
Total score may range from 0 to 148.
|
4 weeks
|
Clinician Domain Likert Scale
Time Frame: 4 weeks
|
an 8 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, and mood by considering the question, "Considering your experience with the patient at this visit, please rate the level of function in each category".
Each domain will be rated on a 7 point Likert Scale where the clinician will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal.
Lower values indicate lesser severity while higher values indicate higher severity.
|
4 weeks
|
Parent Domain Likert Scale
Time Frame: 4 weeks
|
a 9 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, mood, and seizure activity, by considering the question, "Considering your experience with your child over the past 7 days, please rate your child's level of function in each category".
Each domain will be rated on a 7 point Likert Scale where the parent/caregiver will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal.
Lower values indicate lesser severity while higher values indicate higher severity.
|
4 weeks
|
Rett Syndrome Behaviour Questionnaire
Time Frame: 4 weeks
|
a 45-item questionnaire for clinicians to evaluate current behavior and emotional features.
Each item is rated either 0 (not true or not done), 1 (somewhat or sometimes true) and 2 (very true), where higher numbers indicate higher severity.
Total score is summed and may range from 0 to 90.
|
4 weeks
|
Children's Sleep Habits Questionnaire
Time Frame: 4 weeks
|
a 35-item questionnaire for parents to evaluate current sleep and common sleep problems.
The parent/caregiver will rate each item as 1 (rarely), 2 (sometimes), or 3 (usually), where higher scores indicate higher severity.
The parent/caregiver will also indicate if the item is a problem or not.
A total score of the sum of each item and 8 subscale scores (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness) are possible.
Total scores between 0 and 70 are possible, where higher scores indicate more sleep problems.
|
4 weeks
|
Rett Caregiver Burden Inventory Assessment
Time Frame: 4 weeks
|
a 26-item questionnaire for parents to evaluate the burden of care on their quality of life.
The parent/caregiver will rate each item as 0 (never), 1 (rarely), 2 (sometimes), 3 (quite frequently), or 4 (nearly always) where higher scores indicate higher severity.
Total scores between 0 and 104 are possible, where higher scores indicate more caregiver burden.
|
4 weeks
|
Continuous biosensor data
Time Frame: 6-8 weeks
|
2 different non-invasive, wearable devices will be used in the study to determine changes in physiologic measures for the patient in the home environment.
Biosensors will be worn continuously during the screening and treatment period to measure activity, sleep, position, heart rate, and breathing.
|
6-8 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical Global Impression of Improvement
Time Frame: 4 weeks
|
Clinicians will use a 7 point Likert Scale to rate change from baseline symptom severity by addressing the question, "Compared to the patient's condition of Rett syndrome prior to treatment initiation at baseline, the patient's current condition is: 1 very much improved, 2 much improved, 3 minimally improved, 4 no change, 5 minimally worse, 6 much worse, 7 very much worse.
No change would be scored a 0, while improvement would be scored at -1, -2, or -3 and worsening would be scored +1, +2 or +3, depending on the degree of perceived change.
Negative change indicates improvement while positive change indicates worsening
|
4 weeks
|
Motor Behavioral Assessment
Time Frame: 4 weeks
|
a 37-item questionnaire for clinicians to evaluate current behavioral/social, orofacial/respiratory, and motor/physical symptoms.
Each item is rated either 0 (normal or never), 1 (mild or rare), 2 (moderate or occasional), 3 (marked or frequent), 4 (very severe or constant), where higher numbers indicate higher severity.
Each subscale is summed for a subscale score, while the total score is a sum of the subscale scores.
The behavioral/social subscale score may range from 0 to 64; the orofacial/respiratory subscale may range from 0 to 28, and motor/physical subscale may range from 0 to 56.
Total score may range from 0 to 148.
|
4 weeks
|
Clinician Domain Likert Scale
Time Frame: 4 weeks
|
an 8 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, and mood by considering the question, "Considering your experience with the patient at this visit, please rate the level of function in each category".
Each domain will be rated on a 7 point Likert Scale where the clinician will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal.
Lower values indicate lesser severity while higher values indicate higher severity.
|
4 weeks
|
Parent Domain Likert Scale
Time Frame: 4 weeks
|
a 9 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, mood, and seizure activity, by considering the question, "Considering your experience with your child over the past 7 days, please rate your child's level of function in each category".
Each domain will be rated on a 7 point Likert Scale where the parent/caregiver will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal.
Lower values indicate lesser severity while higher values indicate higher severity.
|
4 weeks
|
Rett Syndrome Behaviour Questionnaire
Time Frame: 4 weeks
|
a 45-item questionnaire for clinicians to evaluate current behavior and emotional features.
Each item is rated either 0 (not true or not done), 1 (somewhat or sometimes true) and 2 (very true), where higher numbers indicate higher severity.
Total score is summed and may range from 0 to 90.
|
4 weeks
|
Children's Sleep Habits Questionnaire
Time Frame: 4 weeks
|
a 35-item questionnaire for parents to evaluate current sleep and common sleep problems.
The parent/caregiver will rate each item as 1 (rarely), 2 (sometimes), or 3 (usually), where higher scores indicate higher severity.
The parent/caregiver will also indicate if the item is a problem or not.
A total score of the sum of each item and 8 subscale scores (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness) are possible.
Total scores between 0 and 70 are possible, where higher scores indicate more sleep problems.
|
4 weeks
|
Rett Caregiver Burden Inventory Assessment
Time Frame: 4 weeks
|
a 26-item questionnaire for parents to evaluate the burden of care on their quality of life.
The parent/caregiver will rate each item as 0 (never), 1 (rarely), 2 (sometimes), 3 (quite frequently), or 4 (nearly always) where higher scores indicate higher severity.
Total scores between 0 and 104 are possible, where higher scores indicate more caregiver burden.
|
4 weeks
|
Continuous Biosensor Data
Time Frame: 6-8 weeks
|
2 different non-invasive, wearable devices will be used in the study to determine changes in physiologic measures for the patient in the home environment.
Biosensors will be worn continuously during the screening and treatment period to measure activity, sleep, position, heart rate, and breathing.
|
6-8 weeks
|
EEG Signature
Time Frame: Day 1, Day 15
|
ketamine EEG alpha, beta, gamma, delta and theta waveform signatures compared to placebo to indicate target engagement
|
Day 1, Day 15
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jeffrey Neul, MD, PhD, Vanderbilt University Medical Center
- Study Director: Jana von Hehn, PhD, Rett Syndrome Research Trust
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 12, 2019
Primary Completion (Actual)
November 8, 2021
Study Completion (Actual)
November 22, 2021
Study Registration Dates
First Submitted
August 8, 2018
First Submitted That Met QC Criteria
August 13, 2018
First Posted (Actual)
August 16, 2018
Study Record Updates
Last Update Posted (Actual)
March 27, 2024
Last Update Submitted That Met QC Criteria
March 26, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
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
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Ketamine
Other Study ID Numbers
- Ket-101-RSRT
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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.
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