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

Completed

Phase 2 Results

Trial Description

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

Interventions

  • Placebo Drug
    Intervention Desc: Placebo - No idebenone
    ARM 1: Kind: Experimental
    Label: Group C
    Description: Placebo
    ARM 2: Kind: Experimental
    Label: placebo
    Description: Placebo
  • Idebenone Drug
    Other Names: active drug
    Intervention Desc: 2250 mg/day for 1 month
    ARM 1: Kind: Experimental
    Label: Group A
    Description: Idebenone 900 mg/day
    ARM 2: Kind: Experimental
    Label: Group B
    Description: Idebenone 2250 mg/day
    ARM 3: Kind: Experimental
    Label: Idebenone 900 mg/day
    Description: Idebenone 900 mg/day
    ARM 4: Kind: Experimental
    Label: Idebenone 2250 mg/day
    Description: Idebenone 2250 mg/day

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Pharmacodynamics Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary 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) 1 month No
Secondary To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration 1 month No
Secondary 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) 1 month No
Secondary To assess changes following 1 month treatment with 2 different doses of idebenone with that of placebo in daily activities as assessed by the Quality of Life questionnaires SF36 for adults and PedsQL for children and adolescents 1 month No
Secondary To assess safety and tolerability following 1 month treatment with 2 different doses of idebenone with that of placebo 1 month Yes
Primary Cerebral lactate concentration (as measured by magnetic resonance spectroscopy) Up to 4 weeks from baseline No
Secondary Venous Lactate Concentration Up to 4 weeks from baseline No
Secondary Change in score on the Fatigue Severity Scale (FSS) Baseline and Week 4 No
Secondary Change in score on Quality of Life Questionnaires (SF-36) Baseline and Week 4 No
Primary Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy) Up to 4 weeks from baseline No
Secondary Mean Change in Venous Lactate Concentration Up to 4 weeks from baseline No
Secondary Mean Change in Score on the Fatigue Severity Scale (FSS) Baseline and Week 4 No

Sponsors