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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Recruitment Status : Terminated (Funding withdrawn)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
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

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.


Condition or disease Intervention/treatment Phase
Rett Syndrome Procedure: Intravenous infusion Phase 1

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 : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine for the Treatment of Rett Syndrome: An Exploratory Trial
Study Start Date : November 2015
Actual Primary Completion Date : July 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome
Drug Information available for: Ketamine

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
Procedure: Intravenous infusion
Intravenous infusion of Ketamine

Placebo Comparator: Placebo
Subjects will receive an intravenous infusion of normal saline over the course of 40 minutes
Procedure: Intravenous infusion
Intravenous infusion of Normal Saline




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   5 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02562820


Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Principal Investigator: Daniel Sessler, MD The Cleveland Clinic

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT02562820     History of Changes
Other Study ID Numbers: 15-627
First Posted: September 29, 2015    Key Record Dates
Last Update Posted: August 30, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Syndrome
Rett Syndrome
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action