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

This study has been completed.
Sponsor:
Collaborator:
Santhera Pharmaceuticals
Information provided by (Responsible Party):
Michio Hirano, Columbia University
ClinicalTrials.gov Identifier:
NCT00887562
First received: April 23, 2009
Last updated: August 8, 2016
Last verified: August 2016

April 23, 2009
August 8, 2016
May 2009
July 2012   (final data collection date for primary outcome measure)
Mean Change in 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
  • Mean Change in 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
  • Mean 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).

    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

  • 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
    Other Name: active drug
  • Drug: Idebenone
    2250 mg/day for 1 month
    Other Name: active drug
  • Other: Placebo
    Placebo - No idebenone
    Other Name: No active drug
  • Experimental: Idebenone 900 mg/day
    Idebenone 900 mg/day
    Intervention: Drug: Idebenone
  • Experimental: Idebenone 2250 mg/day
    Idebenone 2250 mg/day
    Intervention: Drug: Idebenone
  • Placebo Comparator: placebo
    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.
 
Completed
27
July 2012
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   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00887562
AAAC9240, SNT-II-007
No
Yes
Once the study has been published, participants will be allowed to know whether they were on placebo or one of the two doses of Idebenone
Michio Hirano, Columbia University
Michio Hirano
Santhera Pharmaceuticals
Principal Investigator: Michio Hirano, MD Columbia University
Columbia University
August 2016

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