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

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ClinicalTrials.gov Identifier: NCT00887562
Recruitment Status : Completed
First Posted : April 24, 2009
Results First Posted : August 10, 2016
Last Update Posted : October 26, 2016
Sponsor:
Collaborator:
Santhera Pharmaceuticals
Information provided by (Responsible Party):
Michio Hirano, Columbia University

Tracking Information
First Submitted Date  ICMJE April 23, 2009
First Posted Date  ICMJE April 24, 2009
Results First Submitted Date  ICMJE December 17, 2015
Results First Posted Date  ICMJE August 10, 2016
Last Update Posted Date October 26, 2016
Study Start Date  ICMJE May 2009
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2016)
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 Measures  ICMJE
 (submitted: April 23, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2016)
  • 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 Measures  ICMJE
 (submitted: April 23, 2009)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE MELAS Syndrome
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 8, 2016)
27
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2009)
21
Actual Study Completion Date  ICMJE July 2012
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00887562
Other Study ID Numbers  ICMJE AAAC9240
SNT-II-007 ( Other Identifier: Santhera )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michio Hirano, Columbia University
Study Sponsor  ICMJE Michio Hirano
Collaborators  ICMJE Santhera Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Michio Hirano, MD Columbia University
PRS Account Columbia University
Verification Date September 2016

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