Clinical trial NCT00887562: Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: MELAS Syndrome
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Santhera Pharmaceuticals
First posted: 2009-04-24
Enrollment: 27
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
timeFrame: Up to 4 weeks from baseline
Secondary outcomes:
measure: Mean Change in Venous Lactate Concentration
timeFrame: Up to 4 weeks from baseline
measure: Mean Change in Score on the Fatigue Severity Scale (FSS)
timeFrame: Baseline and Week 4
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Michio Hirano, MD
role: PRINCIPAL_INVESTIGATOR
References: