Study of Modified Atkins Diet in Kabuki Syndrome

Early Phase 1CompletedNCT04722315

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.10 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Kabuki Syndrome

Interventions

Modified Atkins dietDIETARY_SUPPLEMENT

12 weeks of modified Atkins diet

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Kennedy Krieger Institute

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 12 weeks

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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.

Time frame: 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.

Time frame: 12 weeks