An Exploratory Trial of Ketamine for the Treatment of Rett Syndrome
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Other Indications, Neurology |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 5 - 25 |
| Updated: | 12/17/2016 |
| Start Date: | November 2015 |
| End Date: | November 2017 |
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.
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.
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.
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.
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.
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