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

Tracking Information
First Submitted Date ICMJE	April 23, 2009
First Posted Date ICMJE	April 24, 2009
Results First Submitted Date	December 17, 2015
Results First Posted Date	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	Complete list of historical versions of study NCT00887562 on ClinicalTrials.gov Archive Site
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 Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	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	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	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	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	Sexes Eligible for Study: All
Ages	8 Years to 65 Years (Child, Adult)
Accepts Healthy Volunteers	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	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