Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT00355576
- Lead Sponsor
- Columbia University
- Brief Summary
The objective of this study is to compare two combinations of drugs, minocycline and creatine or celecoxib and creatine, in a phase II trial designed to determine which combination is more effective for ALS.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 86
- A clinical diagnosis of possible, laboratory-supported probable, probable or definite ALS, according to modified EL Escorial criteria
- FVC greater or equal to 60% at the screening visit
- Symptom onset within 5 years
- 21 to 85 years of age
- If patients are taking riluzole, they must be on a stable dose for at least the past thirty days
- A woman of childbearing age, must be nonlactating and surgically sterile or using an effective method of birth control (barrier method) and have a negative pregnancy test
- Able to maintain adequate hydration levels defined as 6-8 cups (8ounces/cup) of water or a non-caffeinated beverage per day
- Willing and able to give signed informed consent that has been approved by an Institutional Review Board (IRB)
- Tracheotomy and mechanical ventilation
- Diagnosis of other neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, etc)
- Unstable medical illness (coronary artery disease, advanced cancer, active esophageal or gastroduodenal ulcers, etc) in the last one year
- Systemic Lupus Erythematosis
- FVC < 60%
- Pregnancy or lactation
- Allergy to minocycline, tetracyclines, celecoxib, sulfonamides, NSAIDS, or creatine
- History of congestive heart failure
- Renal disease [baseline Cr > 1.5 (men) or 1.2 (women)]
- History of significant hepatic disease (baseline AST/ALT or bilirubin > 1.5x normal)
- Use of an investigational agent within thirty days of enrollment
- First degree relative with ALS or gene identified familial ALS
- Inability or unwillingness to maintain adequate daily hydration (defined above)
- Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures.
- History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Minocycline + Creatine Creatine Minocycline 100 mg BID and Creatine 10 g BID Minocycline + Creatine Minocycline Minocycline 100 mg BID and Creatine 10 g BID Celecoxib + Creatine Celecoxib Celecoxib 400 mg BID and Creatine 10 g BID Celecoxib + Creatine Creatine Celecoxib 400 mg BID and Creatine 10 g BID
- Primary Outcome Measures
Name Time Method ALS Functional Rating Scale Revised (ALSFRS-R) completed monthly during trial. Up to 6 months from the start of treatment
- Secondary Outcome Measures
Name Time Method Forced Vital Capacity, Quality of Life, Timed Get Up and Go performed monthly. Survival and measures of safety throughout the trial. Up to 6 months from the start of treatment
Trial Locations
- Locations (19)
UT Southwestern Medical Center
๐บ๐ธDallas, Texas, United States
UMDNJ
๐บ๐ธNew Brunswick, New Jersey, United States
University of Pennsylvania
๐บ๐ธPhiladelphia, Pennsylvania, United States
University of Illinois
๐บ๐ธChicago, Illinois, United States
University of Kansas
๐บ๐ธKansas City, Kansas, United States
California Pacific Medical Center
๐บ๐ธSan Francisco, California, United States
UCLA
๐บ๐ธLos Angeles, California, United States
Medical College of Georgia
๐บ๐ธAugusta, Georgia, United States
Mayo Clinic Florida
๐บ๐ธJacksonville, Florida, United States
Duke University
๐บ๐ธDurham, North Carolina, United States
Washington University
๐บ๐ธSt. Louis, Missouri, United States
Beth Israel
๐บ๐ธNew York, New York, United States
Mayo Clinic Rochester
๐บ๐ธRochester, Minnesota, United States
Columbia University
๐บ๐ธNew York, New York, United States
Phoenix Neurological Associates
๐บ๐ธPhoenix, Arizona, United States
University of New Mexico
๐บ๐ธAlbuquerque, New Mexico, United States
University of Vermont
๐บ๐ธBurlington, Vermont, United States
University of California Irvine
๐บ๐ธOrange, California, United States
Oregon Health and Science University
๐บ๐ธPortland, Oregon, United States