Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Amyotrophic Lateral Sclerosis |
Drug: Celecoxib Drug: Creatine Drug: Minocycline |
Phase 2 |
| Study Type: | Interventional |
| 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 ]
| Enrollment: | 86 |
| Study Start Date: | July 2006 |
| Study Completion Date: | May 2007 |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Minocycline + Creatine
Minocycline 100 mg BID and Creatine 10 g BID
|
Drug: Creatine
10 g BID for either study arm
Other Name: Creatine
Drug: Minocycline
Minocycline 100 mg BID with creatine 10 g BID if randomized to the Minocycline + Creatine study arm
Other Name: Minocycline
|
|
Experimental: Celecoxib + Creatine
Celecoxib 400 mg BID and Creatine 10 g BID
|
Drug: Celecoxib
Celecoxib 400 mg BID with creatine 10 g BID if randomized to the Celecoxib + Creatine study arm.
Other Name: Celecoxib
Drug: Creatine
10 g BID for either study arm
Other Name: Creatine
|
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.
Eligibility| Ages Eligible for Study: | 21 Years to 85 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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.
Contacts and Locations
Show 19 Study Locations| Principal Investigator: | Paul H Gordon, MD | Columbia University |
More Information
Additional Information:
Publications:
| Responsible Party: | Paul H. Gordon, Columbia University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00355576 History of Changes |
| Other Study ID Numbers: | AAAB6334, ALSA ID#920 |
| Study First Received: | July 21, 2006 |
| Last Updated: | January 31, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Columbia University:
|
Amyotrophic Lateral Sclerosis Celecoxib Creatine Minocycline |
Combination Selection ALS Motor Neuron Disease |
Additional relevant MeSH terms:
|
Amyotrophic Lateral Sclerosis Sclerosis Motor Neuron Disease Spinal Cord Diseases Central Nervous System Diseases Nervous System Diseases Neurodegenerative Diseases TDP-43 Proteinopathies Neuromuscular Diseases Proteostasis Deficiencies Metabolic Diseases Pathologic Processes Minocycline Celecoxib Anti-Bacterial Agents |
Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 21, 2013