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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MAD diet group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Modified Atkins diet | Dietary Supplement | 12 weeks of modified Atkins diet |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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. |
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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.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | MAD Diet Group | 10 adult participants with confirmed KMT2D pathogenic mutations. Baseline labs and education about Modified Atkins Diet. Then 12 weeks on a Modified Atkins Diet. Modified Atkins diet: 12 weeks of modified Atkins diet |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | MAD Diet Group | 10 adult participants with confirmed KMT2D pathogenic mutations. Baseline labs and education about Modified Atkins Diet. Then 12 weeks on a Modified Atkins Diet. Modified Atkins diet: 12 weeks of modified Atkins diet |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. A higher score indicates a better performance (range 0-30). | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
12 weeks
Weekly calls to participants and labs (CBC, CMP, UA) at baseline and 12 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MAD Diet Group | 10 adult participants with confirmed KMT2D pathogenic mutations. Baseline labs and education about Modified Atkins Diet. Then 12 weeks on a Modified Atkins Diet. Modified Atkins diet: 12 weeks of modified Atkins diet |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
Single arm pilot study with no control group
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jacqueline Harris | Kennedy Krieger Institute | 6672054295 | harrisjac@kennedykrieger.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 31, 2024 | Mar 13, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 29, 2022 | Jan 24, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| C537705 | Kabuki syndrome |
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15 participants with Kabuki syndrome will receive a 12 week dietary intervention.
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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 |
| 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 |
| 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 |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | 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. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | raw score | 12 weeks |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | raw score | 12 weeks |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | raw score | 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. | Posted | Mean | Standard Deviation | score on a scale | 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. | Not Posted | Jul 2025 | Every 3 weeks for 12 weeks | Participants |
| 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. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
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| 0 |
| 10 |
| 0 |
| 10 |
| 7 |
| 10 |
| Lightheadedness | General disorders | Systematic Assessment |
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| Hypertriglyceridemia or Hypercholesterolemia | Vascular disorders | Systematic Assessment |
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| Low platelets | Blood and lymphatic system disorders | Systematic Assessment |
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| Hypoglycemia | Endocrine disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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