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Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00355576
Recruitment Status : Completed
First Posted : July 24, 2006
Last Update Posted : February 1, 2011
ALS Association
Information provided by:
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Celecoxib Drug: Creatine Drug: Minocycline Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 86 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
Study Start Date : July 2006
Actual Study Completion Date : May 2007

Arm Intervention/treatment
Experimental: Minocycline + Creatine
Minocycline 100 mg BID and Creatine 10 g BID
Drug: Creatine
10 g BID for either study arm

Drug: 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
Drug: Celecoxib
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

Primary Outcome Measures :
  1. ALS Functional Rating Scale Revised (ALSFRS-R) completed monthly during trial. [ Time Frame: Up to 6 months from the start of treatment ]

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00355576

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Sponsors and Collaborators
Columbia University
ALS Association
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Principal Investigator: Paul H Gordon, MD Columbia University
Additional Information:
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Responsible Party: Paul H. Gordon, Columbia University Medical Center Identifier: NCT00355576    
Other Study ID Numbers: AAAB6334
ALSA ID#920 ( Other Identifier: CUMC )
First Posted: July 24, 2006    Key Record Dates
Last Update Posted: February 1, 2011
Last Verified: January 2011
Keywords provided by Columbia University:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Bacterial Agents
Anti-Infective Agents