Clinical Trial of High Dose CoQ10 in ALS - Full Text View

Purpose

The purpose of this study is to determine the efficacy and preferred dose of CoQ10 in individuals with ALS for a possible future phase III study.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis Lou Gehrig's Disease	Drug: coenzyme Q10 Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Clinical Trial of High Dose CoQ10 in ALS

Resource links provided by NLM:

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis Antioxidants

Drug Information available for: Ubidecarenone

Genetic and Rare Diseases Information Center resources: Amyotrophic Lateral Sclerosis

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

Change in the ALS Functional Rating Scale-revised (ALSFRSr) Score. [ Time Frame: 9 months ] [ Designated as safety issue: No ]
The ALSFRSr, a questionnaire-based scale assessing daily living function ranging from 48 (best score) to 0 (worst), was administered to the patient, or to a proxy if the patient could not communicate effectively. Decline was defined as ALSFRSr at baseline minus ALSFRSr at month 9. Thus a positive value indicates worsening.

Secondary Outcome Measures:

The Change Over 9 Months in Forced Vital Capacity; Fatigue Severity Scale; Short Form-36; and 8OH2dG (a Biomarker of Oxidative Stress Measured in a Blood Sample). [ Time Frame: 9 months ] [ Designated as safety issue: No ]


Enrollment:	185
Study Start Date:	April 2005
Study Completion Date:	March 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 2,700 mg CoQ10	Drug: coenzyme Q10 antioxidant and mitochondrial cofactor, given in capsules three times daily Other Names: Coenzyme Q 10 CoQ10
Placebo Comparator: placebo	Drug: Placebo Placebo capsules, indistinguishable from CoQ10 capsules, given three times daily
Experimental: 1,800 mg CoQ10	Drug: coenzyme Q10 antioxidant and mitochondrial cofactor, given in capsules three times daily Other Names: Coenzyme Q 10 CoQ10

Detailed Description:

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder. Available treatment for ALS remains scarce. Oxidative stress and mitochondrial dysfunction have been implicated in the pathophysiology of ALS. Oxidative stress refers to the effects of cell-damaging reactive oxygen species, also known as free radicals. Oxidative stress is thought to contribute to nerve cell loss in ALS. Mitochondria are organelles within each cell that are sometimes called "powerhouses of the cell" because cellular energy metabolism is located within the mitochondria.

Coenzyme Q10 (CoQ10), a mitochondrial cofactor known for its antioxidant properties, has prolonged survival in the mouse model of ALS and has slowed functional decline in another neurodegenerative disorder, Parkinson's disease. The goals of this double-blind, placebo-controlled, two-dose comparison phase II study are to obtain preliminary efficacy data and to select the preferred dose for a larger phase III study.

Participants were randomly assigned to CoQ10 (at two different dose levels) or placebo in the first stage, then the 2,700 mg dose was selected in the second stage. Duration of the trial was 9 months with a total of 7 visits.

Eligibility


Ages Eligible for Study:	21 Years to 85 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinical diagnosis of definite, probable, or laboratory-supported probable ALS
Negative pregnancy test for women of childbearing age and adequate birth control measures
Subjects must be able and willing to give informed consent and must be capable of complying with the trial procedures
Forced Vital Capacity (FVC) >/= 60% of predicted
Age 21 to 85 years, inclusive
Disease duration of less than 5 years
Subjects may take riluzole (without change in dose for more than 30 days before enrollment)
Patients who have taken CoQ10 in the past will be eligible if they stop at least 30 days before enrollment
Patients who have taken vitamin E in the past will be eligible if they stop at least 14 days before enrollment

Exclusion Criteria:

Dependency on mechanical ventilation (non-invasive ventilation > 23 hours)
Severe and unstable concomitant medical or psychiatric illness
Insufficiently controlled diabetes mellitus
Concomitant warfarin therapy
Women who are breast feeding or have a high likelihood of pregnancy
Significant hepatic dysfunction
Forced Vital Capacity (FVC) less than 60%
Exposure to CoQ10 within 30 days of enrollment
Exposure to other experimental medications within 30 days of enrollment
Exposure to vitamin E within 14 days of enrollment
Sensitivity to color additive FD&C Yellow No. 5
Sensitivity to aspirin

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00243932

Locations


United States, Arkansas
University of Arkansas for Medical Sciences, Department of Neurology
Little Rock, Arkansas, United States, 72201
United States, California
California Pacific Medical Center
San Francisco, California, United States, 94101
University of California at San Francisco
San Francisco, California, United States, 94101
United States, Colorado
University of Colorado Health Sciences, Dept of Neurology
Denver, Colorado, United States, 80221
United States, Connecticut
Yale University School of Medicine, Department of Neurology
New Haven, Connecticut, United States, 06501
United States, Illinois
Northwestern University, Department of Neurology,
Chicago, Illinois, United States, 60290
University of Chicago, Department of Neurology
Chicago, Illinois, United States, 60292
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 64116
United States, Kentucky
University of Kentucky, Dept of Neurology, College of Medicine
Lexington, Kentucky, United States, 40201
United States, Massachusetts
Brigham and Women's Hospital , Department of Neurology
Boston, Massachusetts, United States, 02108
Baystate Medical Center, Division of Critical Care Research
Springfield,, Massachusetts, United States, 01101
United States, Minnesota
Minneapolis Medical Research Foundation, ,
Minneapolis, Minnesota, United States, 55421
United States, Missouri
Washington University in St. Louis School of Medicine, Department of Neurology
St. Louis, Missouri, United States, 63101
United States, New York
Columbia Presbyterian Medical Center, The Neurological Institute
New York, New York, United States, 10032
State University of New York Upstate Medical, Neurology Department
Syracuse, New York, United States, 13201
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44101
United States, Pennsylvania
Drexel University, Dept of Neurology
Philadelphia, Pennsylvania, United States, 19113
United States, Texas
University of Texas, Health Science Center at San Antonio, Division of Neurology
San Antonio, Texas, United States, 78201
United States, Vermont
University of Vermont, Neurology Department
Burlington, Vermont, United States, 05401

Sponsors and Collaborators

Columbia University

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators


Principal Investigator:	Petra Kaufmann, MD	Assistant Professor, Division of Neuromuscular Disease, Columbia University Medical Center (Clinical Principal Investigator)
Principal Investigator:	J. L. P. Thompson, Ph.D.	Director, Statistical Analysis Center, Department of Biostatistics, Mailman School of Public Health (Statistical Principal Investigator)
Principal Investigator:	Hiroshi Mitsumoto	Wesley J. Howe Professor of Neurology at the New York Presbyterian Hospital/Columbia University Medical Center

More Information

Publications:

Kaufmann P, Thompson JL, Levy G, Buchsbaum R, Shefner J, Krivickas LS, Katz J, Rollins Y, Barohn RJ, Jackson CE, Tiryaki E, Lomen-Hoerth C, Armon C, Tandan R, Rudnicki SA, Rezania K, Sufit R, Pestronk A, Novella SP, Heiman-Patterson T, Kasarskis EJ, Pioro EP, Montes J, Arbing R, Vecchio D, Barsdorf A, Mitsumoto H, Levin B; QALS Study Group. Phase II trial of CoQ10 for ALS finds insufficient evidence to justify phase III. Ann Neurol. 2009 Aug;66(2):235-44. doi: 10.1002/ana.21743.


Responsible Party:	Hiroshi Mitsumoto, Wesley J. Howe Professor of Neurology at the New York Presbyterian Hospital/Columbia University Medical Center, Columbia University
ClinicalTrials.gov Identifier:	NCT00243932 History of Changes
Other Study ID Numbers:	AAAA1536 R01NS048125
Study First Received:	October 24, 2005
Results First Received:	March 29, 2010
Last Updated:	January 28, 2014
Health Authority:	United States: Food and Drug Administration United States: Federal Government

Keywords provided by Columbia University:


amyotrophic lateral sclerosis ALS Lou Gehrig's disease CoQ10	coenzyme Q10 antioxidants free radicals mitochondrial dysfunction

Additional relevant MeSH terms:


Sclerosis Motor Neuron Disease Amyotrophic Lateral Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies	Metabolic Diseases Antioxidants Coenzyme Q10 Ubiquinone Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Micronutrients Growth Substances Vitamins

ClinicalTrials.gov processed this record on September 27, 2016