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

Phase 2

Completed

Conditions: MELAS Syndrome

Interventions: Other: Placebo
Drug: Idebenone

Registration Number: NCT00887562

Lead Sponsor: Michio Hirano

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebo	Placebo
Idebenone 900 mg/day	Idebenone	Idebenone 900 mg/day
Idebenone 2250 mg/day	Idebenone	Idebenone 2250 mg/day

Primary Outcome Measures

Name	Time	Method
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)	Up to 4 weeks from baseline	To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on cerebral lactate concentration as measured by magnetic resonance spectroscopy (MRS)

Secondary Outcome Measures

Name	Time	Method
Mean Change in Venous Lactate Concentration	Up to 4 weeks from baseline	To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration
Mean Change in Score on the Fatigue Severity Scale (FSS)	Baseline and Week 4	To assess changes following 1 month treatment with 2 different doses of idebenone with that of placebo in fatigue as assessed by the Fatigue Severity Scale (FSS). Scale score minimum is 9 (least fatigue) and maximum is 63 (maximum fatigue). Scores of 36 or less indicate possibility that patient may not be suffering from fatigue, while scores 36 and over suggest suffering from fatigue