Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes (MELAS)
Primary Purpose
MELAS Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Idebenone
Idebenone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for MELAS Syndrome
Eligibility 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
Sites / Locations
- Columbia University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Idebenone 900 mg/day
Idebenone 2250 mg/day
placebo
Arm Description
Idebenone 900 mg/day
Idebenone 2250 mg/day
Placebo
Outcomes
Primary Outcome Measures
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
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
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)
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
Full Information
NCT ID
NCT00887562
First Posted
April 23, 2009
Last Updated
September 20, 2016
Sponsor
Michio Hirano
Collaborators
Santhera Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00887562
Brief Title
Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
Acronym
MELAS
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Michio Hirano
Collaborators
Santhera Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MELAS Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Idebenone 900 mg/day
Arm Type
Experimental
Arm Description
Idebenone 900 mg/day
Arm Title
Idebenone 2250 mg/day
Arm Type
Experimental
Arm Description
Idebenone 2250 mg/day
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Idebenone
Other Intervention Name(s)
active drug
Intervention Description
900 mg/day for 1 month
Intervention Type
Drug
Intervention Name(s)
Idebenone
Other Intervention Name(s)
active drug
Intervention Description
2250 mg/day for 1 month
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
No active drug
Intervention Description
Placebo - No idebenone
Primary Outcome Measure Information:
Title
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
Description
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
Up to 4 weeks from baseline
Secondary Outcome Measure Information:
Title
Mean Change in Venous Lactate Concentration
Description
To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration
Time Frame
Up to 4 weeks from baseline
Title
Mean Change in Score on the Fatigue Severity Scale (FSS)
Description
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
Time Frame
Baseline and Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michio Hirano, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
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