Clinical trial NCT00243932: Clinical Trial of High Dose CoQ10 in ALS
Official title: Clinical Trial of High Dose CoQ10 in ALS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lou Gehrig's Disease
Keywords: amyotrophic lateral sclerosis
ALS
Lou Gehrig's disease
CoQ10
coenzyme Q10
antioxidants
free radicals
mitochondrial dysfunction
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2005-10-25
Enrollment: 185
Sex: ALL
Minimum age (years): 21
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Change in the ALS Functional Rating Scale-revised (ALSFRSr) Score.
timeFrame: 9 months
Secondary outcomes:
measure: Change in Fatigue Severity Scale
timeFrame: 9 months
measure: Change in Forced Vital Capacity
timeFrame: 9 months
measure: Change in Short Form (SF)-36 Score (Physical)
timeFrame: 9 months
measure: Change in Short Form (SF)-36 Score (Mental)
timeFrame: 9 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences, Department of Neurology
state: Arkansas
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences, Dept of Neurology
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine, Department of Neurology
state: Connecticut
city: Chicago
country: United States
facility: Northwestern University, Department of Neurology,
state: Illinois
city: Chicago
country: United States
facility: University of Chicago, Department of Neurology
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Dept of Neurology, College of Medicine
state: Kentucky
city: Boston
country: United States
facility: Brigham and Women's Hospital , Department of Neurology
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center, Division of Critical Care Research
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis Medical Research Foundation, ,
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine, Department of Neurology
state: Missouri
city: New York
country: United States
facility: Columbia Presbyterian Medical Center, The Neurological Institute
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical, Neurology Department
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Drexel University, Dept of Neurology
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas, Health Science Center at San Antonio, Division of Neurology
state: Texas
city: Burlington
country: United States
facility: University of Vermont, Neurology Department
state: Vermont
Study officials:
affiliation: Assistant Professor, Division of Neuromuscular Disease, Columbia University Medical Center (Clinical Principal Investigator)
name: Petra Kaufmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Director, Statistical Analysis Center, Department of Biostatistics, Mailman School of Public Health (Statistical Principal Investigator)
name: J. L. P. Thompson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wesley J. Howe Professor of Neurology at the New York Presbyterian Hospital/Columbia University Medical Center
name: Hiroshi Mitsumoto
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.