Ketones & Mitochondrial Heteroplasmy

Study Overview
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Brief Summary
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The current study is a prospective evaluation of the ability of ketosis to shift mitochondrial DNA (mtDNA) heteroplasmy in subjects harboring a known mutation in their mtDNA at position 3243 (A>G). Subjects will be given supplemental medium chain triglycerides (MCTs) for a period of 6 months. mtDNA heteroplasmy will be measured 3 months prior to treatment, at treatment initiation, and 6 months after initiation. The primary objective of the current study is to determine if there is a shift in heteroplasmy in patients harboring the 3243 A>G mtDNA mutation to a more favorable (higher wild-type) profile while in a state of ketosis.

Detailed Description
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The current study is a prospective evaluation of the ability of ketosis to shift mitochondrial DNA (mtDNA) heteroplasmy in subjects harboring a known pathogenic mutation in their mtDNA at position 3243 (A>G). Subjects will be induced in to ketosis by administration of supplemental medium chain triglycerides (MCTs) for a period of 6 months. mtDNA heteroplasmy will be assessed 3 months prior to treatment, at treatment initiation, and 6 months after initiation. The primary objective of the current study is to determine if there is a shift in heteroplasmy in patients harboring the 3243 A>G mtDNA mutation to a more favorable (higher wild-type) genotypic profile while in a state of ketosis.

Official Title
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Ketones & Mitochondrial Heteroplasmy

Conditions
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MELAS Syndrome, Mitochondrial Diseases

Intervention / Treatment
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* Dietary Supplement: Medium-Chain Triglycerides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is informed and given ample opportunity to consider his/her participation and has given his/her written consent. Subject is willing and able to comply with all trial requirements. Subject harbors the 3243 A>G mtDNA mutation at a level detectable in blood. Female subjects of child-bearing potential must not be pregnant. Female subjects of child-bearing potential (not surgically sterile or 2 years post-menopausal) must also agree to use appropriate contraceptive methods (abstinence, oral, injectable, implantable, or barrier) for the duration of the trial. Subject must not have diabetes mellitus. Exclusion Criteria: Subject is currently participating or has participated within the last 2 months in any clinical trial involving treatment of mitochondrial disorders with MCT supplementation or induction of ketosis. Subject has a medical condition that could reasonably be exacerbated by ketone supplementation (including diabetes mellitus). Subject is unable to give reasonable informed consent/assent. Subject is a pregnant or nursing female.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medium Chain Triglyceride<br> | Dietary Supplement: Medium-Chain Triglycerides<br>* Subjects will take supplemental MCT oil 3 times a day for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heteroplasmy | Blood samples will be used to measure the degree of mitochondrial DNA heteroplasmy | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MELAS, Ketones, Medium Chain Triglycerides, MCT oil, Mitochondrial Disorder, Heteroplasmy, 3243AG, Subject is informed and given ample opportunity to consider his/her participation and has given his/her written consent., Subject is willing and able to comply with all trial requirements., Subject harbors the 3243 A>G mtDNA mutation at a level detectable in blood., Female subjects of child-bearing potential must not be pregnant., Subjects must not have Diabetes Mellitus.