Clinical trial NCT03633058: A Study to Evaluate Ketamine for the Treatment of Rett Syndrome
Official title: A Randomized, Double-blind, Placebo-controlled, Cross-over Study to Assess the Safety, Tolerability and Efficacy of Oral Ketamine for Patients With Rett Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rett Syndrome
Keywords: MECP2
RTT
Retts
ketamine
Lead sponsor: Rett Syndrome Research Trust
Sponsor class: OTHER
Collaborators: name: Vanderbilt University Medical Center
First posted: 2018-08-16
Enrollment: 23
Sex: FEMALE
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients will receive placebo and ketamine for 5 days BID each, in a double-blind treatment order, and will be assessed for 2 weeks after each treatment.
Primary purpose: TREATMENT

Brief summary: This 2 cohort, sequential, ascending dose study will assess the safety, tolerability and efficacy of oral ketamine dosed in a single 5-day BID regimen in addition to placebo, in a 4-week cross-over design in patients with Rett Syndrome. Approximately 12 patients per cohort are anticipated to participate for approximately 8-10 weeks at approximately 7 US study centers.

Detailed description: This study is designed to assess oral ketamine for the treatment of Rett Syndrome and consists of up to 4 ascending dose cohorts, each assessing 1 dose level of ketamine vs placebo. Patients will receive in either order, a 5-day BID regimen of both placebo and the cohort-specified dose level of oral ketamine. Patients may only participate in 1 cohort. Safety and tolerability will be assessed via patient disposition, vital signs, physical examination, adverse events and concomitant medication use. Efficacy will be assessed via physician and caregiver questionnaires and assessments, and continuous, wearable, at-home biosensor data collection. An independent safety committee will review safety data from each cohort to determine if the subsequent ascending dose cohort is warranted. A total of 12 patients per cohort is anticipated at approximately 7 sites. The screening period will last between 2 and 4 weeks, the cross-over treatment period will last 4 weeks, and the safety follow-up period will last 2 weeks. Total patient participation is approximately 8-10 weeks.

Eligibility criteria: Inclusion Criteria:

* Female Rett Syndrome patients diagnosed with Rett Syndrome with a confirmed MECP2 mutation
* between the ages of 6 and 12, inclusive, who have not achieved menarche
* ability to take oral medications
* are generally healthy.

Exclusion Criteria:

* Patients not on stable medication regimens/other types of behavioral, educational, or dietary interventions for at least 4 weeks,
* are taking medications that may interact with ketamine,
* have a condition where increased blood pressure, spinal fluid pressure, or ocular pressure may put the patient at increased risk.

Primary outcomes:
measure: Dose-Limiting Adverse Events
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
measure: Continuous Biosensor Data
timeFrame: 6-8 weeks
measure: Clinical Global Impression of Improvement
timeFrame: 4 weeks
measure: Motor Behavioral Assessment
timeFrame: 4 weeks
measure: Clinician Domain Likert Scale
timeFrame: 4 weeks
measure: Rett Syndrome Behaviour Questionnaire
timeFrame: 4 weeks
measure: Parent Domain Likert Scale
timeFrame: 4 weeks
measure: Children's Sleep Habits Questionnaire
timeFrame: 4 weeks
measure: Rett Caregiver Burden Inventory Assessment
timeFrame: 4 weeks
measure: EEG Signature
timeFrame: Day 1, Day 15
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham School of Medicine
state: Alabama
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
Study officials:
affiliation: Vanderbilt University Medical Center
name: Jeffrey Neul, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rett Syndrome Research Trust
name: Jana von Hehn, PhD
role: STUDY_DIRECTOR
References: