Amyotrophic Lateral SclerosisPhase 3NCT00047723
Minocycline to Treat Amyotrophic Lateral Sclerosis
A Phase 3 study testing minocycline in people with Amyotrophic Lateral Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 30 sites in United States.
Trial summary
The purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (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?
- minocycline
- How many people
- 400 participants
- Where
- 30 sitesUnited States
- Study dates
- Jan 2003to Jan 2007
- Phase
- Phase 3
- 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 laboratory-supported probable, probable or definite ALS, according to modified EL Escorial criteria.
- FVC greater or equal to 75% of predicted.
- Onset of weakness within 3 years prior to enrollment.
- If patients are receiving riluzole they must be on a stable dose for at least the past thirty days.
- Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test (adequate birth control includes use of intra-uterine device or oral contraceptives plus a barrier method, e.g. condom, diaphragm).
- Willing and able to give signed informed consent that has been approved by your Institutional Review Board (IRB).
Who cannot join
- Requirement for tracheotomy ventilation (or non-invasive ventilation > 23 hours/day).
- Diagnosis of other neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, etc).
- FVC < 75% of predicted.
- A clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
- History of renal disease (screening creatinine greater than 1.5).
- History of liver disease (screening alanine aminotransferase greater than 3 times the upper limit of normal).
Show all 18Show fewer
- History of hematologic disease (screening white blood cell count less than 3,800/mm3).
- History of system lupus erythematosis (or screening ANA of 1:160 or greater).
- Treatment with any medications that may cause lupus-like symptoms within 4 weeks of baseline visit (e.g. procainamide, hydralazine).
- History of vestibular disease (excluding benign position vertigo).
- Pregnancy or lactation.
- Allergy to tetracycline antibiotics.
- Use of minocycline within thirty days of enrollment (baseline visit).
- Use of anti-epileptic medications other than gabapentin.
- Limited mental capacity rendering the subject unable to provide written informed consent or comply with evaluation procedures.
- History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
- Use of any investigational drug within the past 30 days (Creatine, Vioxx, Celebrex, Topiramate).
- Women with the potential to become pregnant who are not practicing effective birth control.
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
United States30 sites
University of New Mexico
Albuquerque, New Mexico
University of Vermont
Burlington, Vermont
Carolinas Medical Center
Charlotte, North Carolina
University of Illinois
Chicago, Illinois
Metro Health Clinic
Cleveland, Ohio
University of Texas Southwestern
Dallas, Texas
Univ. of Colorado Health Sciences Center
Denver, Colorado
Duke University
Durham, North Carolina
Methodist Hospital
Houston, Texas
Indiana University School of Medicine
Indianapolis, Indiana
University of Iowa
Iowa City, Iowa
University of California, Irvine
Irvine, California
Mayo Clinic
Jacksonville, Florida
University of Kansas Medical Center
Kansas City, Kansas
University of Kentucky
Lexington, Kentucky
University of California Department of Neurology
Los Angeles, California
Hennepin County Med Center
Minneapolis, Minnesota
University of Minnesota
Minneapolis, Minnesota
UMDNJ/Robert Wood Johnson Medical Center
New Brunswick, New Jersey
Columbia Unversity, Eleanor and Lou Gehrig MDA/ALS Center
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Drexel University College of Medicine, Hahnemann Campus
Philadelphia, Pennsylvania
Oregon Health & Science University
Portland, Oregon
University of Utah
Salt Lake City, Utah
University of Texas Health Sciences Center
San Antonio, Texas
California Pacific Medical Center
San Francisco, California
Mayo Clinic
Scottsdale, Arizona
Virginia Mason Medical Center
Seattle, Washington
Washington University
St Louis, Missouri
Wake Forest University
Winston-Salem, North Carolina
About this study
The purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
Read the detailed description
ALS is a progressive neurodegenerative disorder without cure or known treatment that significantly improves function. Loss of motor neurons in the brain and spinal cord of ALS patients causes the progressive symptoms. Laboratory studies have linked inducible nitric oxide synthase (iNOS) and caspase enzyme activation to motor nerve cell death in ALS. Minocycline-a medication currently approved by the FDA for treatment of bacterial infections-is a tetracycline antibiotic with high central nervous system penetration when taken orally. The drug inhibits the activity of iNOS and caspase enzymes.
Minocycline has been tested and shown to protect nerve cells in many scientific experiments. It reduces cell death and prolongs survival in animal models of ALS, stroke, trauma, Huntington's disease, and Parkinson's disease. It has been shown to be beneficial in many different animal experiments of ALS, conducted in Europe, Canada and the United States.
Minocycline has been tested in 2 preliminary human trials and has been shown to be safe in patients with ALS. It has been well tolerated in conjunction with riluzole (Rilutek), the only currently FDA-approved medication for ALS.
This trial is the final important step in determining whether minocycline improves the course of ALS. The principle objective of this clinical trial is to determine whether minocycline slows disease progression and helps maintain function in patients with ALS. This multi-center placebo-controlled study will select patients early in the course of ALS, when a neuroprotective therapy may be most beneficial. The study will measure change in function (as detected by ALSFRS-R scores), strength, pulmonary function, survival, and quality of life. Participants will undergo monthly outpatient evaluations and analysis of laboratory and adverse events. This is a 13-month study.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- minocycline
- Keywords
- ALS, amyotrophic lateral sclerosis, minocycline
- Medical subject headings
- Amyotrophic Lateral Sclerosis, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
minocyclineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.
Secondary outcomes (1)
Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2002 (estimated)
- Study startJan 2003
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 National Institute of Neurological Disorders and Stroke (NINDS)The 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Double blind
- Enrolment
- 400 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Paul H. Gordon, M.D.,, Principal investigator, Associate Medical Director, Eleanor and Lou Gehrig MDA/ALS Center, Columbia University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00047723
- Sponsor's protocol ID
- R01NS045294
- Status last verified
- Dec 2007
- First submitted
- 16 Oct 2002
- Last updated
- 21 Dec 2007
- Results posted
- No
Publications
Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, Neville HE, Boylan K, Mozaffar T, Belsh JM, Ravits J, Bedlack RS, Graves MC, McCluskey LF, Barohn RJ, Tandan R; Western ALS Study Group. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007 Dec;6(12):1045-53. doi: 10.1016/S1474-4422(07)70270-3. Epub 2007 Nov 5.
PubMed 17980667
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minocycline to Treat Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT00047723
- Acronym / sponsor ID
- R01NS045294
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, amyotrophic lateral sclerosis, minocycline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 400 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Jan 2003
- Study completion
- Jan 2007 (actual)
- First posted
- 17 Oct 2002 (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 purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
Detailed description
ALS is a progressive neurodegenerative disorder without cure or known treatment that significantly improves function. Loss of motor neurons in the brain and spinal cord of ALS patients causes the progressive symptoms. Laboratory studies have linked inducible nitric oxide synthase (iNOS) and caspase enzyme activation to motor nerve cell death in ALS. Minocycline-a medication currently approved by the FDA for treatment of bacterial infections-is a tetracycline antibiotic with high central nervous system penetration when taken orally. The drug inhibits the activity of iNOS and caspase enzymes.
Minocycline has been tested and shown to protect nerve cells in many scientific experiments. It reduces cell death and prolongs survival in animal models of ALS, stroke, trauma, Huntington's disease, and Parkinson's disease. It has been shown to be beneficial in many different animal experiments of ALS, conducted in Europe, Canada and the United States.
Minocycline has been tested in 2 preliminary human trials and has been shown to be safe in patients with ALS. It has been well tolerated in conjunction with riluzole (Rilutek), the only currently FDA-approved medication for ALS.
This trial is the final important step in determining whether minocycline improves the course of ALS. The principle objective of this clinical trial is to determine whether minocycline slows disease progression and helps maintain function in patients with ALS. This multi-center placebo-controlled study will select patients early in the course of ALS, when a neuroprotective therapy may be most beneficial. The study will measure change in function (as detected by ALSFRS-R scores), strength, pulmonary function, survival, and quality of life. Participants will undergo monthly outpatient evaluations and analysis of laboratory and adverse events. This is a 13-month study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Double blind
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- A clinical diagnosis of laboratory-supported probable, probable or definite ALS, according to modified EL Escorial criteria.
- FVC greater or equal to 75% of predicted.
- Onset of weakness within 3 years prior to enrollment.
- If patients are receiving riluzole they must be on a stable dose for at least the past thirty days.
- Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test (adequate birth control includes use of intra-uterine device or oral contraceptives plus a barrier method, e.g. condom, diaphragm).
Key exclusion criteria (18 listed)
- Requirement for tracheotomy ventilation (or non-invasive ventilation > 23 hours/day).
- Diagnosis of other neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, etc).
- FVC < 75% of predicted.
- A clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
- History of renal disease (screening creatinine greater than 1.5).
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 |
|---|---|---|
| minocycline | Drug | – |
Primary outcome
Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.
1 secondary outcome
Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival
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 21 Dec 2007.
- Results publication: PubMed 17980667Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, Neville HE, Boylan K, Mozaffar T, Belsh JM, Ravits J, Bedlack RS, Graves MC, McCluskey LF, Barohn RJ, Tandan R; Western ALS Study Group. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007 Dec;6(12):1045-53. doi: 10.1016/S1474-4422(07)70270-3. Epub 2007 Nov 5.
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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, M.D., principal investigator
Associate Medical Director, Eleanor and Lou Gehrig MDA/ALS Center, Columbia University Medical Center
30 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing minocycline in people with Amyotrophic Lateral Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 30 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 6 inclusion and 18 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 21 Dec 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.. 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 NCT00047723, which also lists 1 linked publication.
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 21 Dec 2007.