- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04722315
Study of Modified Atkins Diet in Kabuki Syndrome
January 8, 2024 updated by: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Pilot Clinical Trial of Modified Atkins Diet for Kabuki Syndrome
Animal models of Kabuki syndrome have showed a reversal of the cognitive phenotype with ketogenic diet.
Modified Atkins diet is safer and easier tolerated than full ketogenic diet and still has the histone deacetylase inhibition believed to be responsible for the cognitive improvement.
This study aims to examine a small number of adults with Kabuki syndrome before and after 12 weeks on a modified Atkins diet to determine if there is any cognitive improvement and if the diet can be tolerated.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
Consented participants will participate in an initial 2 day study visit.
These participants will undergo cognitive and neurobehavioral testing and also will have baseline labs drawn and will meet with a Johns Hopkins nutritionist trained in modified Atkins diet for education.
The labs are standard of care for diet initiation to rule out contraindications to the diet.
Participants and/or their caregivers will keep a daily diet log and will be asked to download the free Carb Manager application onto their smartphone.
They will send the logs and data back weekly.
Participants will be given urine ketone strips and asked to use and record in their diet log twice weekly.
Participants will have blood and urine samples collected locally every 3 weeks and sent back to study team to measure Beta-hydroxybutyrate, metabolic studies and methylation.
Participants will return to Baltimore at the end of 12 weeks for a one day visit to repeat the cognitive assessment protocol, neurobehavioral measures, and repeat the initial and follow up lab tests.
Study Type
Interventional
Enrollment (Estimated)
15
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21205
- Kennedy Krieger Institute
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:We will recruit 15 total participants with clinically-definite and genetically-confirmed Kabuki syndrome type 1 age 18 years and older. . will also be required.
- Clinical diagnosis of KS will be made based on recently published consensus diagnosis criteria
- Genetic confirmation of a pathogenic mutation in KMT2D
Exclusion Criteria:
- presence of another known genetic syndrome
- a health problem that would make a modified Atkins diet harmful
- inability to travel to Baltimore for 2 visits separated by 12 weeks
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MAD diet group
15 adult participants with confirmed KMT2D pathogenic mutations.
Baseline labs and education about Modified Atkins Diet.
Then 12 weeks on a Modified Atkins Diet.
Weekly urine dips for ketones and diet logs.
Blood draw every 3 weeks.
|
12 weeks of modified Atkins diet
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Benton Judgement of Line Orientation
Time Frame: 12 weeks
|
Established measure to determine visuospatial perception.
There are 30 items and each item is worth 1 point.
Will assess change in score from baseline to post-diet.
|
12 weeks
|
Brief Visuospatial memory test
Time Frame: 12 weeks
|
Established measure to determine visuospatial memory.
Scores range from 0 to 36 and a higher score indicates more correct responses.
Will assess change in score from baseline to post-diet.
|
12 weeks
|
NIH Toolbox Picture Sequence Memory
Time Frame: 12 weeks
|
Established measure to determine visuospatial memory.
Scaled scores based on age have a mean of 100 and a standard deviation of 15 and higher scores indicate more correct responses.
Will assess change in this score from baseline to post-diet.
|
12 weeks
|
Beery Developmental Test of Visual Motor Integration
Time Frame: 12 weeks
|
Established measure to determine visuomotor integration.
Scaled scores based on age have a mean of 100 and a standard deviation of 15 with a floor of 45 and higher scores indicate more correct responses.
Will assess change in this score from baseline to post-diet.
|
12 weeks
|
Beery Developmental Test of Visual Perception
Time Frame: 12 weeks
|
Established measure to determine visual perception.
Scaled scores based on age have a mean of 100 and a standard deviation of 15 with a floor of 45 and higher scores indicate more correct responses.
Will assess change in this score from baseline to post-diet.
|
12 weeks
|
Wechsler Intelligence Scale for Children -V Block Design
Time Frame: 12 weeks
|
Established measure to determine visuospatial processing.
Scaled scores which will be scaled to age 16:11 for all participants have a mean of 10 and a standard deviation of 1.5 with a range of 1-19 and higher scores indicate more correct responses.
Will assess change in this score from baseline to post-diet.
|
12 weeks
|
Hopkins Verbal Learning Test
Time Frame: 12 weeks
|
Established measure to determine verbal memory.
Scores range from 0 to 36 and a higher score indicates more correct responses.
Will assess change in score from baseline to post-diet.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DNA Methylation analysis
Time Frame: Every 3 weeks for 12 weeks
|
Measure genome-wide methylation signature in blood of participants.
To obtain genome-scale methylation measurements, bisulfite treated DNA from patient blood samples will be processed on the Infinium HumanMethylation450 BeadChip at the Johns Hopkins SNP Center in accordance with the manufacturer's recommendation.
The Infinium HumanMethylation450 BeadChip measures DNA methylation levels at 485,512 loci across the genome.
The array data will then be analyzed to get the proportion of methylation at a given CpG site from 0 to 1.
These will be logit transformed to create M-values.
Kabuki syndrome is known to have a unique signature methylation profile (determined by M-values across loci) that can be detected in blood.
This genome wide DNA methylation will be done every 3 weeks to determine whether this signature changes with dietary therapy.
|
Every 3 weeks for 12 weeks
|
Caregiver behavior rating scales: GAS-ID
Time Frame: 12 weeks
|
Rating scale for anxiety consists of 27 items with scores ranging from 0-70 with higher scores indicating more anxiety.
Performed at baseline and post-diet.
|
12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2021
Primary Completion (Estimated)
February 25, 2024
Study Completion (Estimated)
December 1, 2024
Study Registration Dates
First Submitted
November 24, 2020
First Submitted That Met QC Criteria
January 21, 2021
First Posted (Actual)
January 25, 2021
Study Record Updates
Last Update Posted (Actual)
January 10, 2024
Last Update Submitted That Met QC Criteria
January 8, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 00250195
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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