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An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome

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ClinicalTrials.gov Identifier: NCT02562820
Recruitment Status : Terminated (Funding withdrawn)
First Posted : September 29, 2015
Last Update Posted : August 30, 2017
Information provided by (Responsible Party):
The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE September 28, 2015
First Posted Date  ICMJE September 29, 2015
Last Update Posted Date August 30, 2017
Study Start Date  ICMJE November 2015
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 28, 2015)
Complications [ Time Frame: 90 minutes after infusion ]
Number complications during the infusion and immediate recovery period
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2015)
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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome
Official Title  ICMJE Ketamine for the Treatment of Rett Syndrome: An Exploratory Trial
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Rett Syndrome
Intervention  ICMJE
  • Procedure: Intravenous infusion
    Intravenous infusion of Ketamine
  • Procedure: Intravenous infusion
    Intravenous infusion of Normal Saline
Study Arms  ICMJE
  • 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
    Intervention: Procedure: Intravenous infusion
  • Placebo Comparator: Placebo
    Subjects will receive an intravenous infusion of normal saline over the course of 40 minutes
    Intervention: Procedure: Intravenous infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 28, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: September 28, 2015)
Actual Study Completion Date  ICMJE July 2017
Actual Primary Completion Date July 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Rett syndrome diagnosis based on the 2010 RTT diagnostic criteria, as determined by review of clinical records, and
  2. Pathogenic mutation in the MECP2 gene, and
  3. Breathing score of 3 or greater on RSBQ, and
  4. Age 5-25 years.

Exclusion Criteria:

  1. Ongoing clinical regression as determined by review of clinical records and consultation with parents, or
  2. Seizure within one week of study session, or
  3. Unstable systemic illness other than Rett syndrome, or
  4. Clinically important variations in medication use.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 5 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02562820
Other Study ID Numbers  ICMJE 15-627
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party The Cleveland Clinic
Original Responsible Party Same as current
Current Study Sponsor  ICMJE The Cleveland Clinic
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel Sessler, MD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP