Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes

NCT ID: NCT00887562

Last Updated: 2016-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2012-07-31

Brief Summary

The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.

Detailed Description

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes), a progressive and often devastating multisystem disorder, is most commonly associated with mitochondrial Deoxyribonucleic acid (mtDNA) point mutation at nucleotide 3243. Seizures, cognitive deterioration, and neurobehavioral abnormalities are frequent features of this disease which typically shortens life expectancy. Idebenone, an ATP production modulator and antioxidant, improves neurological function in Friedreich's ataxia, a disease also associated with mitochondrial dysfunction.

Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group.

The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). Patients will receive idebenone (900 mg/day or 2250 mg/day) or matching placebo for one month. The primary outcome measure is cerebral lactate levels measured by Magnetic Resonance Spectroscopy (MRS), a biomarker associated with disease worsening. This study will help the investigators to determine if there is sufficient signal to proceed to efficacy studies. Also it will provide additional information on the safety and tolerability of two different doses of idebenone in MELAS.

Conditions

MELAS Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Idebenone 900 mg/day

Idebenone 900 mg/day

Group Type: EXPERIMENTAL

Idebenone

Intervention Type: DRUG

900 mg/day for 1 month

Idebenone 2250 mg/day

Idebenone 2250 mg/day

Group Type: EXPERIMENTAL

Idebenone

Intervention Type: DRUG

2250 mg/day for 1 month

placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo - No idebenone

Interventions

Idebenone

900 mg/day for 1 month

Intervention Type: DRUG

Idebenone

2250 mg/day for 1 month

Intervention Type: DRUG

Placebo

Placebo - No idebenone

Intervention Type: OTHER

Other Intervention Names

active drug; active drug; No active drug

Eligibility Criteria

Inclusion Criteria

• Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss)
• Cerebral lactate level equal to or greater than 5.0 i.u. at baseline
• Patients at least 8 and < 65 years of age at baseline
• Patients with a body weight > 37 kg/82 lbs at baseline
• Stable co-medication/vitamins/supplements within 1 month prior to baseline
• Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication
• Negative urine pregnancy test at screening and baseline (female patients of childbearing potential)

Exclusion Criteria

• Contraindication to MRS (e.g. metal implant, claustrophobia)
• Stroke like event within 2 months prior to baseline
• Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline
• Inadequate contraception use
• Pregnancy and/or breast-feeding
• Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine
• Current abuse of drugs or alcohol
• Participation in a trial of another investigational drug within the last month
• Other factor that, in the investigator's opinion, excludes the patient from entering the study

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Santhera Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Michio Hirano

OTHER

Sponsor Role: lead

Responsible Party

Michio Hirano

Professor of Neurology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michio Hirano, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

SNT-II-007

Identifier Type: OTHER

Identifier Source: secondary_id

AAAC9240

Identifier Type: -

Identifier Source: org_study_id