- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00887562
Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes (MELAS)
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 Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo
Placebo
|
Placebo - No idebenone
Other Names:
|
Experimental: Idebenone 900 mg/day
|
900 mg/day for 1 month
Other Names:
2250 mg/day for 1 month
Other Names:
|
Experimental: Idebenone 2250 mg/day
|
900 mg/day for 1 month
Other Names:
2250 mg/day for 1 month
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
Up to 4 weeks from baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
Up to 4 weeks from baseline
|
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 |
Baseline and Week 4
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Cerebrovascular Disorders
- Central Nervous System Diseases
- Nervous System Diseases
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Metabolism, Inborn Errors
- Brain Diseases, Metabolic
- Mitochondrial Diseases
- Brain Diseases, Metabolic, Inborn
- Cerebral Small Vessel Diseases
- Acid-Base Imbalance
- Mitochondrial Encephalomyopathies
- Mitochondrial Myopathies
- Brain Diseases
- MELAS Syndrome
- Acidosis
- Acidosis, Lactic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Micronutrients
- Antioxidants
- Ubiquinone
- Idebenone
Other Study ID Numbers
- AAAC9240
- SNT-II-007 (Other Identifier: Santhera)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on MELAS Syndrome
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The Hospital for Sick ChildrenCompleted
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Eunice Kennedy Shriver National Institute of Child...Unknown
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Second Affiliated Hospital, School of Medicine,...Not yet recruiting
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Hospital Universitario 12 de OctubreActive, not recruiting
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Jesús González de la Aleja TejeraCompleted
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Abliva ABCompletedMitochondrial Diseases | Mitochondrial Myopathies | MELAS Syndrome | Mitochondrial Respiratory Chain DeficienciesUnited Kingdom
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