An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome

Brief Title

An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome

Official Title

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 Phase

Phase 1

Study Type

Interventional

Primary Outcome

Behavioral phenomena requiring intervention

Secondary Outcome

 Exploratory - Rett Syndrome Behavior Questionnaire (RSBQ)

Condition

Rett Syndrome

Intervention

Intravenous infusion

Study Arms / Comparison Groups

 Ketamine

Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Procedure

Estimated Enrollment

4

Start Date

November 2015

Completion Date

July 2017

Primary Completion Date

July 2017

Eligibility Criteria

        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.
      

Gender

Female

Ages

5 Years - 25 Years

Accepts Healthy Volunteers

No

Contacts

Daniel Sessler, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT02562820

Organization ID

15-627

Responsible Party

Sponsor

Study Sponsor

The Cleveland Clinic

Study Sponsor

Daniel Sessler, MD, Principal Investigator, The Cleveland Clinic

Verification Date

August 2017