Study of Modified Atkins Diet in Kabuki Syndrome

Kabuki Syndrome Clinical Trial

Official title:

Pilot Clinical Trial of Modified Atkins Diet for Kabuki Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04722315
• Other study ID #: 00250195
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: April 1, 2021
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: December 2024
• Est. primary completion date: February 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Abnormalities, Multiple
• Hematologic Diseases
• Kabuki Syndrome
• Syndrome
• Vestibular Diseases

Intervention

Dietary Supplement:
• Modified Atkins diet
12 weeks of modified Atkins diet

Locations

Country	Name	City	State
United States	Kennedy Krieger Institute	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Benton Judgement of Line Orientation	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
Primary	Brief Visuospatial memory test	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
Primary	NIH Toolbox Picture Sequence Memory	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
Primary	Beery Developmental Test of Visual Motor Integration	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
Primary	Beery Developmental Test of Visual Perception	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
Primary	Wechsler Intelligence Scale for Children -V Block Design	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
Primary	Hopkins Verbal Learning Test	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	DNA Methylation analysis	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
Secondary	Caregiver behavior rating scales: GAS-ID	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