This trial is active, not recruiting.

Condition melas syndrome
Treatments idebenone, placebo
Phase phase 2
Sponsor Michio Hirano
Collaborator Santhera Pharmaceuticals
Start date May 2009
End date July 2012
Trial size 21 participants
Trial identifier NCT00887562, AAAC9240, SNT-II-007


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacodynamics study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Idebenone 900 mg/day
900 mg/day for 1 month
Idebenone 2250 mg/day
2250 mg/day for one month
(Placebo Comparator)
Placebo - No idebenone

Primary Outcomes

Cerebral lactate concentration (as measured by magnetic resonance spectroscopy)
time frame: Up to 4 weeks from baseline

Secondary Outcomes

Venous Lactate Concentration
time frame: Up to 4 weeks from baseline
Change in score on the Fatigue Severity Scale (FSS)
time frame: Baseline and Week 4
Change in score on Quality of Life Questionnaires (SF-36)
time frame: Baseline and Week 4

Eligibility Criteria

Male or female participants from 8 years up to 65 years old.

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

Additional Information

Official title A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes
Principal investigator Michio Hirano, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2013.
Information provided to ClinicalTrials.gov by Columbia University.