- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02562820
An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome
Ketamine for the Treatment of Rett Syndrome: An Exploratory Trial
Rett Syndrome (RTT) is a complex disorder resulting from mutations in a gene encoding the MeCP2 protein. Currently, there are no methods to fix the abnormal gene, however, animal studies suggest that the symptoms of RTT can be treated.
Ketamine is a sedative or anesthetic, depending on the dose. The drug is approved by the US Food and Drug Administration (FDA) and is commonly used in children and adults. Animal studies and case reports in humans suggest that ketamine may reduce the symptoms of Rett syndrome. The purpose of this study is to determine the safety and efficacy of ketamine for treating breathing and behavioral symptoms of RTT.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Families will be asked to maintain current prescription medications during the expected three-month duration of the study. However, clinically indicated medication alterations will naturally be permitted and recorded.
Each participant will experience four study days, separated by about a month. On three of the study days participants will be given Ketamine, and on the other day they will be given saline placebo.
Studies will be conducted in the Cleveland Clinic's General Clinical Research Unit which is an NIH-sponsored unit designed for studies such as this. Subjects will be admitted on the first day of each study sequence, and discharged the subsequent day. Study subjects will arrive at approximately 8:00 AM. Age, weight and height will be determined and prescription medications will be recorded. Subjects will be fitted with sensors for recording respiration, heart rate and brain electrical activity (electroencephalogram, or EEG). Treatment administration will start at noon. To avoid potential effects of circadian variation, treatment administration will start at the same time for each study day in each subject. Because the half-life of Ketamine is short (t1/2 = 10-15 minutes for sedation/anesthesia), we expect participating patients to be fully recovered from any potential sedating effects of Ketamine within an hour or two.
Each subject will be randomized to receive 3 of the 5 doses of Ketamine 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg] plus placebo, for a total of 4 periods (visits). Ordering of the treatments will be randomized, with patients earlier in the study to receive lower doses of Ketamine.
The study drug will be given as a constant infusion at 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg over the course of 40 minutes.
Apnea/breath-hold index, hyperventilation and cardio-respiratory coupling indices will be measured by polysomnography (PSG) before, during and after each treatment.
EEG will be recorded before, during and after each treatment.
Auditory evoked potentials (AEP) will be recorded on the day after each treatment.
Rett Syndrome Behavior Questionnaire (RSBQ) will be administered multiple times after each treatment, first in the hospital and then at home.
Repetitive Behavior Scale-Revised (RBSR) will be administered on the day after each treatment.
Before infusion and one hour after infusion, a few mL of peripheral blood will be sampled to measure bio-markers. Blood will be centrifuged and plasma will be frozen for subsequent analysis.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Rett syndrome diagnosis based on the 2010 RTT diagnostic criteria, as determined by review of clinical records, and
- Pathogenic mutation in the MECP2 gene, and
- Breathing score of 3 or greater on RSBQ, and
- Age 5-25 years.
Exclusion Criteria:
- Ongoing clinical regression as determined by review of clinical records and consultation with parents, or
- Seizure within one week of study session, or
- Unstable systemic illness other than Rett syndrome, or
- Clinically important variations in medication use.
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 |
---|---|
Experimental: Ketamine
Subjects will receive intravenous infusion of a 0.1, 0.5, 1.0, 2.0 or 4.5 mg/kg dose over the course of 40 minutes
|
Intravenous infusion of Ketamine
Intravenous infusion of Normal Saline
|
Placebo Comparator: Placebo
Subjects will receive an intravenous infusion of normal saline over the course of 40 minutes
|
Intravenous infusion of Ketamine
Intravenous infusion of Normal Saline
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Behavioral phenomena requiring intervention
Time Frame: From time of admission until time of discharge during any particular study visit, typically within 36 hours of admission.
|
Occurrence of agitation, irritability, or worsening of pre-existing symptoms.
|
From time of admission until time of discharge during any particular study visit, typically within 36 hours of admission.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory - Rett Syndrome Behavior Questionnaire (RSBQ)
Time Frame: On the day following study drug infusion at each visit (30 - 36 hours after admission for each visit).
|
A formal score obtained by administering the RSBQ to the subject's parent/guardian before and after every study visit.
|
On the day following study drug infusion at each visit (30 - 36 hours after admission for each visit).
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Daniel Sessler, MD, The Cleveland Clinic
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
Additional Relevant MeSH Terms
Other Study ID Numbers
- 15-627
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 Intravenous infusion
-
Novartis PharmaceuticalsCompletedPigmented Villonodular Synovitis | PVNS | Giant Cell Tumor of the Tendon Sheath | GCCTS | Tenosynovial Giant Cell Tumor Localized or Diffused Type | GCTSUnited States, Switzerland
-
Mabwell (Shanghai) Bioscience Co., Ltd.RecruitingAdvanced Malignant NeoplasmChina
-
Mabwell (Shanghai) Bioscience Co., Ltd.Not yet recruitingSolid Tumors
-
University of FloridaCompleted
-
Erasme University HospitalCompletedSevere OsteoporosisBelgium
-
Navy General Hospital, BeijingXijing Hospital; Peking Union Medical College Hospital; Chinese PLA General Hospital and other collaboratorsUnknownAcute Myocardial Infarction
-
Medical University of ViennaKlinik FavoritenRecruitingVolume Overload | Hyperosmolality | Electrolyte ImbalanceAustria
-
University of Sao PauloUnknownDiabetes Mellitus, Insulin-DependentBrazil
-
The First Hospital of Jilin UniversityCompleted