Modified Atkins Diet for Kabuki Syndrome

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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

Disqualifiers: Other genetic syndromes, Health problems, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a modified Atkins diet, easier to follow than a full ketogenic diet, can improve cognitive function in adults with Kabuki syndrome. Kabuki syndrome is a genetic disorder affecting many parts of the body, and researchers aim to enhance brain function by influencing specific proteins through the diet. Ideal candidates have Kabuki syndrome confirmed by genetic testing and can travel to Baltimore for two visits. As an Early Phase 1 trial, this research seeks to understand how the diet impacts cognitive function, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the Modified Atkins Diet is safe for adults with Kabuki syndrome?

Research has shown that the Modified Atkins Diet is generally safe and manageable for most people. For over ten years, both children and adults have used this diet primarily to help with epilepsy. Some individuals on this diet have experienced common side effects such as constipation and higher cholesterol levels, but these are usually manageable. Importantly, the Modified Atkins Diet is considered easier to follow than a full ketogenic diet while still offering potential brain benefits. Although specific safety data for Kabuki syndrome is not yet available, the diet's success in other conditions suggests it is a safe option to consider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The Modified Atkins Diet (MAD) is unique for treating Kabuki Syndrome because it focuses on dietary changes rather than traditional medication or therapy approaches. While most treatments for Kabuki Syndrome primarily address symptoms through medical or supportive therapies, MAD aims to influence underlying metabolic processes by increasing ketone production. Researchers are excited about this diet because it offers a non-pharmacological approach that could potentially improve cognitive and metabolic outcomes in individuals with Kabuki Syndrome, providing a new avenue for managing this complex condition.

What evidence suggests that the Modified Atkins diet might be an effective treatment for Kabuki syndrome?

Research suggests that the ketogenic diet may improve brain function in animal studies of Kabuki syndrome. This improvement likely links to the diet's impact on certain brain processes that can enhance memory. Participants in this trial will follow the Modified Atkins Diet, a safer and easier version of the ketogenic diet that still offers similar benefits. In a study of children with epilepsy on the Modified Atkins Diet, more than half showed significant improvements in thinking and memory. Although direct evidence for people with Kabuki syndrome is limited, these findings indicate possible benefits for brain function. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Kabuki syndrome type 1, confirmed both clinically and genetically. Participants must be able to follow a modified Atkins diet and travel to Baltimore twice over 12 weeks. Those with health issues that make the diet risky or another genetic syndrome cannot join.

Inclusion Criteria

My Kaposi's sarcoma diagnosis follows the latest consensus criteria.

My genetic test shows a mutation in the KMT2D gene.

I am 18 or older with a confirmed diagnosis of Kabuki syndrome type 1.

Exclusion Criteria

I have a condition that makes the modified Atkins diet unsafe for me.

I cannot travel to Baltimore for two appointments 12 weeks apart.

I have been diagnosed with a genetic syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 days

1 visit (in-person)

Treatment

Participants follow a Modified Atkins Diet for 12 weeks with regular monitoring and assessments

12 weeks

Weekly data submission, blood and urine samples every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Modified Atkins diet

Trial Overview The study tests if a modified Atkins diet can improve cognitive function in adults with Kabuki syndrome. It's based on animal studies showing benefits from ketogenic diets. Over 12 weeks, participants will switch to this safer, more tolerable diet variant.

How Is the Trial Designed?

Group I: MAD diet group Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

93

Recruited

25,200+

Published Research Related to This Trial

The modified Atkins diet, used since 2003 for treating refractory epilepsy, has shown similar effectiveness to the traditional ketogenic diet while being more tolerable for patients, with around 400 patients reported across over 30 studies.

This diet can be initiated in a clinical setting without the need for fasting or hospitalization, making it a more accessible option for both children and adults with intractable seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A decade of the modified Atkins diet (2003–2013): Results, insights, and future directions. Kossoff, EH., Cervenka, MC., Henry, BJ., et al.[2019]

The modified Atkins diet (MAD) was tested in a prospective study involving five children aged 4-18 years with Sturge-Weber syndrome, showing promising results in managing intractable seizures over a 6-month period.

All participants achieved urinary ketosis and experienced improvements in seizure frequency, with three children reporting more than a 50% reduction in seizures, suggesting that MAD may be a safer alternative to the ketogenic diet for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of the modified Atkins diet for Sturge-Weber syndrome. Kossoff, EH., Borsage, JL., Comi, AM.[2010]

In a study of 87 children on the modified Atkins diet for epilepsy, 55% of those who continued for over 6 months experienced more than a 50% improvement in seizures, and 35% became seizure-free after an average of 19.9 months.

The diet showed similar efficacy to short-term studies and long-term ketogenic diets, but side effects included increased lipid levels and gastrointestinal issues, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of children treated with the modified Atkins diet. Chen, W., Kossoff, EH.[2017]

The Modified Atkins Diet (MAD) significantly improved seizure control in patients with intractable epilepsy, reducing daily seizure frequency from an average of 13.29 to 2.71 over nine months.

Mothers of the patients also experienced a significant improvement in their quality of life across all domains measured, indicating that MAD not only benefits the patients but also positively impacts their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with MAD on children with epilepsy in Egypt after classic KD failure. El Rashidy, OF., Nassar, MF., El Gendy, YG., et al.[2018]

In a study involving four adult patients with drug-resistant epilepsy, the modified Atkins diet led to a significant average reduction of 35% in serum concentrations of antiepileptic drugs (AEDs) after 12 weeks, indicating a potential pharmacokinetic interaction.

This reduction in AED levels could have clinical implications for patients, suggesting that careful monitoring of AED serum concentrations is necessary when implementing the modified Atkins diet as an add-on therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified Atkins diet may reduce serum concentrations of antiepileptic drugs. Kverneland, M., Taubøll, E., Selmer, KK., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04722315?cond=%22Kabuki%20syndrome%22&rank=2

Study of Modified Atkins Diet in 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11134553/

Ketogenic diet modifies ribosomal protein dysregulation in ... A 12-year-old boy with KS, suffering from recurrent episodes of cognitive decline, exhibited improved cognitive function and neuropsychological ...

3. withpower.com withpower.com/trial/early-phase-1-hematologic-diseases-3-2021-24f7b

Modified Atkins Diet for Kabuki Syndrome In a study of 87 children on the modified Atkins diet for epilepsy, 55% of those who continued for over 6 months experienced more than a 50% improvement in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845236/

Molecular insights of KMT2D and clinical aspects of Kabuki ... This scoping review examines KMT2D's role in gene expression regulation across various species, cell types, and contexts.

5. kabukisyndromefoundation.org kabukisyndromefoundation.org/research/kabuki-syndrome-therapeutic-pipeline/

The Kabuki Syndrome Therapeutic Pipeline Researchers have shown that a ketogenic diet can improve memory in a Kabuki syndrome type 1 mouse model [3]. This benefit is likely due to BHB ( ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK62111/

Kabuki Syndrome - GeneReviews® - NCBI Bookshelf A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome. Proc Natl Acad Sci USA. 2017;114:125-130. [PMC free ...

7. pnas.org pnas.org/doi/10.1073/pnas.1611431114

A ketogenic diet rescues hippocampal memory defects in ... Here we demonstrate rescue of hippocampal memory defects and deficiency of adult neurogenesis in a mouse model of Kabuki syndrome by imposing a ketogenic diet.