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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.


Sponsor: Michio Hirano

Current Primary Outcome: Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy) [ Time Frame: 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)


Original Primary Outcome: 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) [ Time Frame: 1 month ]

Current Secondary Outcome:

  • Mean Change in Venous Lactate Concentration [ Time Frame: 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) [ Time Frame: 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



Original Secondary Outcome:

  • To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration [ Time Frame: 1 month ]
  • 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) [ Time Frame: 1 month ]
  • 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 [ Time Frame: 1 month ]
  • To assess safety and tolerability following 1 month treatment with 2 different doses of idebenone with that of placebo [ Time Frame: 1 month ]


Information By: Columbia University

Dates:
Date Received: April 23, 2009
Date Started: May 2009
Date Completion:
Last Updated: September 20, 2016
Last Verified: September 2016