Amyotrophic Lateral SclerosisPhase 2NCT00355576
Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
A Phase 2 study testing Celecoxib, Creatine and Minocycline in people with Amyotrophic Lateral Sclerosis, run by Columbia University at 19 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Celecoxib, Creatine and Minocycline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 19 sitesUnited States
- Study dates
- Jul 2006to May 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Medical College of Georgia
Augusta, Georgia, 30912
University of Vermont
Burlington, Vermont, 05405
University of Illinois
Chicago, Illinois, 60637
UT Southwestern Medical Center
Dallas, Texas, 75390
Duke University
Durham, North Carolina, 27705
Mayo Clinic Florida
Jacksonville, Florida, 32224
University of Kansas
Kansas City, Kansas, 66160
UCLA
Los Angeles, California, 90095
UMDNJ
New Brunswick, New Jersey, 08901
Beth Israel
New York, New York, 10003
Columbia University
New York, New York, 10032
University of California Irvine
Orange, California, 92868
University of Pennsylvania
Philadelphia, Pennsylvania, 19107
Phoenix Neurological Associates
Phoenix, Arizona, 85006
Oregon Health and Science University
Portland, Oregon, 97201
Mayo Clinic Rochester
Rochester, Minnesota, 55905
California Pacific Medical Center
San Francisco, California, 94115
Washington University
St Louis, Missouri, 63110
About this study
Official title: Phase II Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Celecoxib, Creatine, Minocycline
- Keywords
- Amyotrophic Lateral Sclerosis, Celecoxib, Creatine, Minocycline, Combination, Selection, ALS, Motor Neuron Disease
- Medical subject headings
- Amyotrophic Lateral Sclerosis, cyclopia sequence, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CelecoxibDrug
Celecoxib 400 mg BID with creatine 10 g BID if randomized to the Celecoxib + Creatine study arm.
CreatineDrug
10 g BID for either study arm
MinocyclineDrug
Minocycline 100 mg BID with creatine 10 g BID if randomized to the Minocycline + Creatine study arm
| Study group | Role | What they receive |
|---|---|---|
| Minocycline + Creatine | Experimental | Minocycline 100 mg BID and Creatine 10 g BID Receives: Drug: Creatine; Drug: Minocycline |
| Celecoxib + Creatine | Experimental | Celecoxib 400 mg BID and Creatine 10 g BID Receives: Drug: Celecoxib; Drug: Creatine |
What is being measured
The primary outcome is the main question the study is designed to answer.
ALS Functional Rating Scale Revised (ALSFRS-R) completed monthly during trial.
Measured: Up to 6 months from the start of treatment
Secondary outcomes (1)
Forced Vital Capacity, Quality of Life, Timed Get Up and Go performed monthly. Survival and measures of safety throughout the trial.
Measured: Up to 6 months from the start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2006 (estimated)
- Study startJul 2006
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- ALS Association, Pfizer
- Investigators
- Paul H Gordon, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00355576
- Sponsor's protocol ID
- AAAB6334
- Other IDs
- ALSA ID#920
- Status last verified
- Jan 2011
- First submitted
- 21 Jul 2006
- Last updated
- 1 Feb 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Klivenyi P, Kiaei M, Gardian G, Calingasan NY, Beal MF. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem. 2004 Feb;88(3):576-82. doi: 10.1046/j.1471-4159.2003.02160.x.
PubMed 14720207Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol. 2003 Feb;53(2):267-70. doi: 10.1002/ana.10476.
PubMed 12557297Cheung YK, Gordon PH, Levin B. Selecting promising ALS therapies in clinical trials. Neurology. 2006 Nov 28;67(10):1748-51. doi: 10.1212/01.wnl.0000244464.73221.13.
PubMed 17130405
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Combination Therapy Selection Trial in Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT00355576
- Acronym / sponsor ID
- AAAB6334
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Amyotrophic Lateral Sclerosis, Celecoxib, Creatine, Minocycline, Combination, Selection, ALS, Motor Neuron Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- ALS Association, Pfizer
- Study start
- Jul 2006
- Study completion
- May 2007 (actual)
- First posted
- 24 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Minocycline + Creatine | Experimental | Drug: Creatine, Drug: MinocyclineMinocycline 100 mg BID and Creatine 10 g BID |
| Celecoxib + Creatine | Experimental | Drug: Celecoxib, Drug: CreatineCelecoxib 400 mg BID and Creatine 10 g BID |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- 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%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CelecoxibCelecoxib 400 mg BID with creatine 10 g BID if randomized to the Celecoxib + Creatine study arm. | Drug | Celecoxib + Creatine |
| Creatine10 g BID for either study arm | Drug | Celecoxib + Creatine, Minocycline + Creatine |
| MinocyclineMinocycline 100 mg BID with creatine 10 g BID if randomized to the Minocycline + Creatine study arm | Drug | Minocycline + Creatine |
Primary outcome
ALS Functional Rating Scale Revised (ALSFRS-R) completed monthly during trial.
Time frame: Up to 6 months from the start of treatment
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2011.
- Background: PubMed 14720207Klivenyi P, Kiaei M, Gardian G, Calingasan NY, Beal MF. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem. 2004 Feb;88(3):576-82. doi: 10.1046/j.1471-4159.2003.02160.x.
- Background: PubMed 12557297Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol. 2003 Feb;53(2):267-70. doi: 10.1002/ana.10476.
- Background: PubMed 17130405Cheung YK, Gordon PH, Levin B. Selecting promising ALS therapies in clinical trials. Neurology. 2006 Nov 28;67(10):1748-51. doi: 10.1212/01.wnl.0000244464.73221.13.
- Eleanor and Lou Gehrig MDA/ALS Research Center at Columbia University websiteLink provided by the sponsor.
- ALS Association WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul H Gordon, MD principal investigator
Columbia University
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Celecoxib, Creatine and Minocycline in people with Amyotrophic Lateral Sclerosis, run by Columbia University at 19 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALS Functional Rating Scale Revised (ALSFRS-R) completed monthly during trial. (time frame: Up to 6 months from the start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00355576, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2011.