Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate Ketamine for the Treatment of Rett Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03633058
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
Vanderbilt University Medical Center
Information provided by (Responsible Party):
Rett Syndrome Research Trust

Brief Summary:
This 4 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 and up to approximately 48 patients in total are anticipated to participate for approximately 8-10 weeks at approximately 7 US study centers.

Condition or disease Intervention/treatment Phase
Rett Syndrome Drug: Ketamine Phase 2

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 and up to 48 patients in total 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: double-blind
Primary Purpose: Treatment
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
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: 0.75 mg/kg
ketamine will be dosed orally twice daily for 5 days at 0.75 mg/kg, in addition to 5 days of placebo
Drug: Ketamine
oral ketamine dosed twice daily for 5 days
Other Name: Ketalar

Experimental: 1.5 mg/kg
ketamine will be dosed orally twice daily for 5 days at 0.75 mg/kg, in addition to 5 days of placebo
Drug: Ketamine
oral ketamine dosed twice daily for 5 days
Other Name: Ketalar

Experimental: 3.0 mg/kg
ketamine will be dosed orally twice daily for 5 days at 3.0 mg/kg, in addition to 5 days of placebo
Drug: Ketamine
oral ketamine dosed twice daily for 5 days
Other Name: Ketalar

Experimental: 4.5 mg/kg
ketamine will be dosed orally twice daily for 5 days at 4.5 mg/kg, in addition to 5 days of placebo
Drug: Ketamine
oral ketamine dosed twice daily for 5 days
Other Name: Ketalar




Primary Outcome Measures :
  1. Dose-Limiting Adverse Events [ Time Frame: 6 weeks ]
    the incidence of treatment-emergent adverse events will be summarized compared to placebo


Secondary Outcome Measures :
  1. Clinical Global Impression of Improvement [ Time Frame: 4 weeks ]
    Clinicians will use a 7 point Likert Scale to rate change from baseline symptom severity by addressing the question, "Compared to the patient's condition of Rett syndrome prior to treatment initiation at baseline, the patient's current condition is: 1 very much improved, 2 much improved, 3 minimally improved, 4 no change, 5 minimally worse, 6 much worse, 7 very much worse. No change would be scored a 0, while improvement would be scored at -1, -2, or -3 and worsening would be scored +1, +2 or +3, depending on the degree of perceived change. Negative change indicates improvement while positive change indicates worsening

  2. Motor Behavioral Assessment [ Time Frame: 4 weeks ]
    a 37-item questionnaire for clinicians to evaluate current behavioral/social, orofacial/respiratory, and motor/physical symptoms. Each item is rated either 0 (normal or never), 1 (mild or rare), 2 (moderate or occasional), 3 (marked or frequent), 4 (very severe or constant), where higher numbers indicate higher severity. Each subscale is summed for a subscale score, while the total score is a sum of the subscale scores. The behavioral/social subscale score may range from 0 to 64; the orofacial/respiratory subscale may range from 0 to 28, and motor/physical subscale may range from 0 to 56. Total score may range from 0 to 148.

  3. Clinician Domain Likert Scale [ Time Frame: 4 weeks ]
    an 8 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, and mood by considering the question, "Considering your experience with the patient at this visit, please rate the level of function in each category". Each domain will be rated on a 7 point Likert Scale where the clinician will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal. Lower values indicate lesser severity while higher values indicate higher severity.

  4. Parent Domain Likert Scale [ Time Frame: 4 weeks ]
    a 9 category (domain) questionnaire to assess current hand function, walking, verbal and non-verbal communication, comprehension, attention, behavior problems, mood, and seizure activity, by considering the question, "Considering your experience with your child over the past 7 days, please rate your child's level of function in each category". Each domain will be rated on a 7 point Likert Scale where the parent/caregiver will select 1 of 7 choices: 1 normal, 2 borderline abnormal, 3 mildly abnormal, 4 moderately abnormal, 5 markedly abnormal, 6 severely abnormal, 7 extremely abnormal. Lower values indicate lesser severity while higher values indicate higher severity.

  5. Rett Syndrome Behaviour Questionnaire [ Time Frame: 4 weeks ]
    a 45-item questionnaire for clinicians to evaluate current behavior and emotional features. Each item is rated either 0 (not true or not done), 1 (somewhat or sometimes true) and 2 (very true), where higher numbers indicate higher severity. Total score is summed and may range from 0 to 90.

  6. Children's Sleep Habits Questionnaire [ Time Frame: 4 weeks ]
    a 35-item questionnaire for parents to evaluate current sleep and common sleep problems. The parent/caregiver will rate each item as 1 (rarely), 2 (sometimes), or 3 (usually), where higher scores indicate higher severity. The parent/caregiver will also indicate if the item is a problem or not. A total score of the sum of each item and 8 subscale scores (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness) are possible. Total scores between 0 and 70 are possible, where higher scores indicate more sleep problems.

  7. Rett Caregiver Burden Inventory Assessment [ Time Frame: 4 weeks ]
    a 26-item questionnaire for parents to evaluate the burden of care on their quality of life. The parent/caregiver will rate each item as 0 (never), 1 (rarely), 2 (sometimes), 3 (quite frequently), or 4 (nearly always) where higher scores indicate higher severity. Total scores between 0 and 104 are possible, where higher scores indicate more caregiver burden.

  8. Continuous biosensor data [ Time Frame: 6-8 weeks ]
    2 different non-invasive, wearable devices will be used in the study to determine changes in physiologic measures for the patient in the home environment. Biosensors will be worn continuously during the screening and treatment period to measure activity, sleep, position, heart rate, and breathing.


Other Outcome Measures:
  1. EEG signature [ Time Frame: Day 1, Day 15 ]
    ketamine EEG alpha, beta, gamma, delta and theta waveform signatures compared to placebo to indicate target engagement



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 12 Years   (Child)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female Rett Syndrome patients diagnosed with typical 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.

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): NCT03633058


Contacts
Layout table for location contacts
Contact: Jana von Hehn, PhD 203-444-1587 jana@rsrt.org

Locations
Layout table for location information
United States, Alabama
University of Alabama Birmingham School of Medicine Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Judy Combs    205-996-4935    combsj@uab.edu   
Principal Investigator: Alan Percy, MD         
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Trusha Rajgor, PhD    720-777-8499    Trusha.Rajgor@childrenscolorado.org   
Principal Investigator: Timothy Benke, MD, PhD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Thao Tran    312-942-2815    Thao_Tran@rush.edu   
Principal Investigator: Elizabeth Berry-Kravis, MD, PhD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Grace Bazin    617-355-1495    Grace.Bazin@childrens.harvard.edu   
Principal Investigator: David Lieberman, MD, PhD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Casey Gorman    267-426-5171    GormanC@email.chop.edu   
Principal Investigator: Eric Marsh, MD, PhD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37203
Contact: Diana Coman       diana.l.coman@vumc.org   
Principal Investigator: Jeffrey Neul, MD, PhD         
Sponsors and Collaborators
Rett Syndrome Research Trust
Vanderbilt University Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey Neul, MD, PhD Vanderbilt University Medical Center
Study Director: Jana von Hehn, PhD Rett Syndrome Research Trust

Layout table for additonal information
Responsible Party: Rett Syndrome Research Trust
ClinicalTrials.gov Identifier: NCT03633058     History of Changes
Other Study ID Numbers: Ket-101-RSRT
First Posted: August 16, 2018    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rett Syndrome Research Trust:
MECP2
RTT
Retts
ketamine

Additional relevant MeSH terms:
Layout table for 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