Clinical Trial of High Dose CoQ10 in ALS

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis; Lou Gehrig's Disease
• Intervention / Treatment: Drug: coenzyme Q10; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: Placebo; Placebo capsules, indistinguishable from CoQ10 capsules, given three times daily
Experimental: 2,700 mg CoQ10	Drug: coenzyme Q10; antioxidant and mitochondrial cofactor, given in capsules three times daily; Other Names: CoQ10; Coenzyme Q 10
Experimental: 1,800 mg CoQ10	Drug: coenzyme Q10; antioxidant and mitochondrial cofactor, given in capsules three times daily; Other Names: CoQ10; Coenzyme Q 10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the ALS Functional Rating Scale-revised (ALSFRSr) Score.	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.	9 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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).	9 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: 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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: October 24, 2005
• First Submitted That Met QC Criteria: October 24, 2005
• First Posted (Estimate): October 25, 2005

Study Record Updates

• Last Update Posted (Estimate): February 28, 2014
• Last Update Submitted That Met QC Criteria: January 28, 2014
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: ALS; amyotrophic lateral sclerosis; CoQ10; antioxidants; coenzyme Q10; Lou Gehrig's disease; mitochondrial dysfunction; free radicals
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Coenzyme Q10; Ubiquinone
• Other Study ID Numbers: AAAA1536; R01NS048125 (U.S. NIH Grant/Contract)