Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis

This study has been completed.
Sponsor:
Collaborators:
ALS Association
Pfizer
Information provided by:
Columbia University
ClinicalTrials.gov Identifier:
NCT00355576
First received: July 21, 2006
Last updated: January 31, 2011
Last verified: January 2011
  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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00355576

  Show 19 Study Locations
Sponsors and Collaborators
Columbia University
ALS Association
Pfizer
Investigators
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
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 21, 2014