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

This study has been completed.
Santhera Pharmaceuticals
Information provided by (Responsible Party):
Michio Hirano, Columbia University Identifier:
First received: April 23, 2009
Last updated: September 20, 2016
Last verified: September 2016
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.

Condition Intervention Phase
MELAS Syndrome Drug: Idebenone Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Michio Hirano, Columbia University:

Primary Outcome Measures:
  • 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)

Secondary Outcome Measures:
  • 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

Enrollment: 27
Study Start Date: May 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idebenone 900 mg/day
Idebenone 900 mg/day
Drug: Idebenone
900 mg/day for 1 month
Other Name: active drug
Experimental: Idebenone 2250 mg/day
Idebenone 2250 mg/day
Drug: Idebenone
2250 mg/day for 1 month
Other Name: active drug
Placebo Comparator: placebo
Other: Placebo
Placebo - No idebenone
Other Name: No active drug

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.


Ages Eligible for Study:   8 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00887562

United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Michio Hirano
Santhera Pharmaceuticals
Principal Investigator: Michio Hirano, MD Columbia University
  More Information

Responsible Party: Michio Hirano, Professor of Neurology, Columbia University Identifier: NCT00887562     History of Changes
Other Study ID Numbers: AAAC9240
SNT-II-007 ( Other Identifier: Santhera )
Study First Received: April 23, 2009
Results First Received: December 17, 2015
Last Updated: September 20, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Brain Diseases
Acidosis, Lactic
MELAS Syndrome
Mitochondrial Encephalomyopathies
Central Nervous System Diseases
Nervous System Diseases
Acid-Base Imbalance
Metabolic Diseases
Mitochondrial Myopathies
Muscular Diseases
Musculoskeletal Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Neuromuscular Diseases
Vascular Diseases
Cardiovascular Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Mitochondrial Diseases
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Growth Substances processed this record on September 25, 2017