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

MELAS Syndrome Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00887562
• Other study ID #: AAAC9240
• Secondary ID: SNT-II-007
• Status: Completed
• Phase: Phase 2
• First received: April 23, 2009
• Last updated: August 8, 2016
• Start date: May 2009
• Est. completion date: July 2012

Study information

• Verified date: August 2016
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acidosis
• Acidosis, Lactic
• Brain Diseases
• MELAS Syndrome
• Mitochondrial Encephalomyopathies

Intervention

Drug:
• Idebenone
900 mg/day for 1 month
• Idebenone
2250 mg/day for 1 month

Other:
• Placebo
Placebo - No idebenone

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Michio Hirano	Santhera Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Up to 4 weeks from baseline	No
Secondary	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	Up to 4 weeks from baseline	No
Secondary	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	Baseline and Week 4	No