Ketones & Mitochondrial Heteroplasmy

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.

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.