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Study of Modified Atkins Diet in Kabuki Syndrome

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ClinicalTrials.gov Identifier: NCT04722315
Recruitment Status : Recruiting
First Posted : January 25, 2021
Last Update Posted : May 9, 2022
Sponsor:
Information provided by (Responsible Party):
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Kabuki Syndrome Dietary Supplement: Modified Atkins diet Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 15 participants with Kabuki syndrome will receive a 12 week dietary intervention.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Clinical Trial of Modified Atkins Diet for Kabuki Syndrome
Actual Study Start Date : April 1, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT04722315


Locations
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United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Jacqueline Harris, MD    667-205-4295      
Contact: Jennifer Johnson    667-205-4295    johnsonjen@kennedykrieger.org   
Sponsors and Collaborators
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
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Responsible Party: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT04722315    
Other Study ID Numbers: 00250195
First Posted: January 25, 2021    Key Record Dates
Last Update Posted: May 9, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Vestibular Diseases
Hematologic Diseases
Abnormalities, Multiple
Syndrome
Disease
Pathologic Processes
Congenital Abnormalities
Labyrinth Diseases
Ear Diseases
Otorhinolaryngologic Diseases