Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase II Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis|
- ALS Functional Rating Scale Revised (ALSFRS-R) completed monthly during trial. [ Time Frame: Up to 6 months from the start of treatment ] [ Designated as safety issue: No ]
- Forced Vital Capacity, Quality of Life, Timed Get Up and Go performed monthly. Survival and measures of safety throughout the trial. [ Time Frame: Up to 6 months from the start of treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2006|
|Study Completion Date:||May 2007|
Experimental: Minocycline + Creatine
Minocycline 100 mg BID and Creatine 10 g BID
10 g BID for either study armDrug: Minocycline
Minocycline 100 mg BID with creatine 10 g BID if randomized to the Minocycline + Creatine study arm
Experimental: Celecoxib + Creatine
Celecoxib 400 mg BID and Creatine 10 g BID
Celecoxib 400 mg BID with creatine 10 g BID if randomized to the Celecoxib + Creatine study arm.Drug: Creatine
10 g BID for either study arm
Excess free radicals, energy mishandling, excitotoxicity, activation of cell death pathways and inflammation likely all contribute to neurodegeneration in ALS. Past trials may have been negative in part because they tested single agents, usually influencing only one mechanism of cell death. Combinations of agents that affect different and multiple mechanisms of neurodegeneration may be necessary to reach meaningful outcomes in trials of ALS.
This trial has several unique features. First, it compares the neuroprotective potential of two combinations of agents that impact multiple mechanisms of cell death. The combinations of minocycline/creatine and celecoxib/creatine are the only agents that have had additive effects in the mouse model of ALS, reducing neurodegeneration and prolonging survival more than individual agents alone. Second, it uses an important new phase II selection trial design to determine which combination is superior. Not only does this trial test combination therapy, but there is no placebo, so everyone who enrolls in the trial will receive active treatment.
Minocycline, creatine and celecoxib have been tested individually and have been shown to be safe in patients with ALS. This will be the first time human trials will be conducted with combinations of minocycline/creatine and celecoxib/creatine.
We will compare combinations of drugs in a phase II trial design to determine which combination is superior. If successful, this trial will lead directly to a phase III trial of the selected combination. If the design is found useful, this trial will lead to larger phase II selection trials assessing greater numbers of agents simultaneously, thereby improving the efficiency of drug screening in ALS.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00355576
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|Principal Investigator:||Paul H Gordon, MD||Columbia University|