Ketones & Mitochondrial Heteroplasmy

Early Phase 1

Completed

• Conditions: MELAS Syndrome; Mitochondrial Diseases
• Interventions: Dietary Supplement: Medium-Chain Triglycerides

• Registration Number: NCT01252979
• Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-01
• Study First Submitted QC: 2010-12-01
• Study First Posted: 2010-12-03
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-03
• Last Update Posted: 2012-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

1. Subject is informed and given ample opportunity to consider his/her participation and has given his/her written consent.
2. Subject is willing and able to comply with all trial requirements.
3. Subject harbors the 3243 A>G mtDNA mutation at a level detectable in blood.
4. 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.
5. Subject must not have diabetes mellitus.

Exclusion Criteria

1. 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.
2. Subject has a medical condition that could reasonably be exacerbated by ketone supplementation (including diabetes mellitus).
3. Subject is unable to give reasonable informed consent/assent.
4. Subject is a pregnant or nursing female.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Medium Chain Triglyceride	Medium-Chain Triglycerides	-

Primary Outcome Measures

Name	Time	Method
Heteroplasmy	9 months	Blood samples will be used to measure the degree of mitochondrial DNA heteroplasmy

Trial Locations

Locations (1)

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States