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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Santhera Pharmaceuticals
Information provided by (Responsible Party):
Michio Hirano, Columbia University
ClinicalTrials.gov Identifier:
NCT00887562
First received: April 23, 2009
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Columbia University:

Primary Outcome Measures:
  • Cerebral lactate concentration (as measured by magnetic resonance spectroscopy) [ Time Frame: Up to 4 weeks from baseline ] [ Designated as safety issue: No ]
    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:
  • Venous Lactate Concentration [ Time Frame: Up to 4 weeks from baseline ] [ Designated as safety issue: No ]
    To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration

  • Change in score on the Fatigue Severity Scale (FSS) [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    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)

  • Change in score on Quality of Life Questionnaires (SF-36) [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
    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


Enrollment: 21
Study Start Date: May 2009
Estimated Study Completion Date: February 2014
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Idebenone 900 mg/day
Drug: Idebenone
900 mg/day for 1 month
Experimental: Group B
Idebenone 2250 mg/day
Drug: Idebenone
2250 mg/day for one month
Placebo Comparator: Group C
Placebo
Other: Placebo
Placebo - No idebenone

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.

  Eligibility

Ages Eligible for Study:   8 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887562

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

No publications provided

Responsible Party: Michio Hirano, Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier: NCT00887562     History of Changes
Other Study ID Numbers: AAAC9240, SNT-II-007
Study First Received: April 23, 2009
Last Updated: February 13, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Mitochondrial Encephalomyopathies
Mitochondrial Myopathies
Muscular Diseases
Mitochondrial Diseases
Acidosis, Lactic
MELAS Syndrome
Acidosis
Acid-Base Imbalance
Metabolic Diseases
Musculoskeletal Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Neuromuscular Diseases
Vascular Diseases
Cardiovascular Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Idebenone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014