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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

April 23, 2009
February 13, 2013
May 2009
July 2012   (final data collection date for primary outcome measure)
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)
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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00887562 on ClinicalTrials.gov Archive Site
  • 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
  • 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 ] [ 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) [ Time Frame: 1 month ] [ 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 [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • To assess safety and tolerability following 1 month treatment with 2 different doses of idebenone with that of placebo [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
MELAS Syndrome
  • Drug: Idebenone
    900 mg/day for 1 month
  • Drug: Idebenone
    2250 mg/day for one month
  • Other: Placebo
    Placebo - No idebenone
  • Experimental: Group A
    Idebenone 900 mg/day
    Intervention: Drug: Idebenone
  • Experimental: Group B
    Idebenone 2250 mg/day
    Intervention: Drug: Idebenone
  • Placebo Comparator: Group C
    Placebo
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
21
February 2014
July 2012   (final data collection date for primary outcome measure)

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
Both
8 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00887562
AAAC9240, SNT-II-007
No
Michio Hirano, Columbia University
Michio Hirano
Santhera Pharmaceuticals
Principal Investigator: Michio Hirano, MD Columbia University
Columbia University
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP