Clinical Trial of High Dose CoQ10 in ALS

Study Overview
=================
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.

Official Title
-----------------
Clinical Trial of High Dose CoQ10 in ALS

Conditions
-----------------
Amyotrophic Lateral Sclerosis, Lou Gehrig's Disease

Intervention / Treatment
-----------------
* Drug: coenzyme Q10
* Drug: Placebo


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2,700 mg CoQ10<br> | Drug: coenzyme Q10<br>* antioxidant and mitochondrial cofactor, given in capsules three times daily<br>* Other names: CoQ10;|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* Placebo capsules, indistinguishable from CoQ10 capsules, given three times daily<br>|
| Experimental: 1,800 mg CoQ10<br> | Drug: coenzyme Q10<br>* antioxidant and mitochondrial cofactor, given in capsules three times daily<br>* Other names: CoQ10;|

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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
amyotrophic lateral sclerosis, ALS, Lou Gehrig's disease, CoQ10, coenzyme Q10, antioxidants, free radicals, mitochondrial dysfunction