Study of Modified Atkins Diet in Kabuki Syndrome

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: Completed
• Conditions: Kabuki Syndrome
• Intervention / Treatment: Dietary supplement: Modified Atkins diet

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 (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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.	Dietary supplement: Modified Atkins diet; 12 weeks of modified Atkins diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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. A higher score indicates a better performance (range 0-30).	12 weeks
Brief Visuospatial Memory Test	Established measure to determine visuospatial memory. Immediate scores range from 0 to 36 and a higher score indicates more correct responses. Delayed scores range from 0 to 12 and a higher score indicates more correct responses. Will assess change in score from baseline to post-diet.	12 weeks
Beery Developmental Test of Visual Motor Integration	Established measure to determine visuomotor integration. Since these were all adults, raw scores were used. Range is 1-27. 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	Established measure to determine visual perception. Since these were all adults, raw scores were used. Range is 1-27. 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	Established measure to determine visuospatial processing. Since these were all adults, raw scores were used. Range is 0-66. Higher scores indicate more correct responses. Will assess change in this score from baseline to post-diet. Will assess change in this score from baseline to post-diet.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): January 26, 2024
• Study Completion (Actual): March 12, 2025

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): May 13, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Congenital Abnormalities; Otorhinolaryngologic Diseases; Ear Diseases; Labyrinth Diseases; Syndrome; Vestibular Diseases; Hematologic Diseases; Abnormalities, Multiple
• 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