Multiple SclerosisPhase 3NCT00467584
Aspirin for Treatment of Multiple Sclerosis-Related Fatigue
A Phase 3 study testing High Dose Aspirin (1300 mg/day) and Low Dose Aspirin (162 mg/day) in people with Multiple Sclerosis and Fatigue, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to determine whether aspirin is effective for treatment of fatigue caused by multiple sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Fatigue
- What is being tested?
- High Dose Aspirin (1300 mg/day) and Low Dose Aspirin (162 mg/day)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Sep 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed relapsing-remitting or secondary progressive multiple sclerosis,
- Ambulatory for distance of at least 100 meters without gait assistance,
- Persistent fatigue for at least 8 weeks that is not attributable to causes other than MS, and
- Will be able to complete questionnaires and cognitive testing.
Who cannot join
- Other evident causes for fatigue:
- Untreated depression or screening Center for Epidemiologic Studies Depression (CES-D) scale greater than 28
- Significant cognitive impairment (Baseline Short Test of Mental Status score of less than 29/38)
- Narcolepsy, uncontrolled sleep apnea, or other primary sleep disorder judged to be likely a major contributor to fatigue
- Screening Epsworth Sleepiness Scale score greater than 15
- Uncontrolled hypothyroidism or anemia
Show all 30Show fewer
- Other medical illness judged by the investigator to affect the participant's fatigue complaints including current viral, bacterial, mycobacterial, or fungal infection
- MS Disease Activity and Treatment:
- Clinical exacerbations within 2 weeks prior to screening visit
- Corticosteroid use within 4 weeks prior to screening visit
- Beta-interferon, glatiramer acetate, immunosuppressant drugs (mitoxantrone, azathioprine, etc.) are permitted if a stable dose has been used for greater than or equal to 4 weeks and there is no temporal association of drug administration with perceived fatigue; elective on-study dose/regimen changes are not permitted
- Current or Recent Fatigue Therapy and Other Medications:
- Use of more than two doses of ASA (aspirin) greater than 81 mg/d within 2 weeks of screening visit
- Use of MS fatigue medications within 2 weeks of screening visit (including amantadine or Central Nervous System stimulants such as modafinil, methylphenidate, and pemoline)
- Symptomatic medications (antidepressants, anti-spasticity agents, non-narcotic analgesics) are permitted if a stable dose has been used for >4 weeks prior to screening for antidepressants and >2 weeks prior to screening for other symptomatic therapies and there is no temporal association of drug administration with perceived fatigue; elective on-study dose changes are not permitted.
- Current use of acetazolamide, antiplatelet agents or anticoagulants, COX-2 inhibitors, methotrexate, oral hypoglycemic medications
- Medical Contraindications to ASA use:
- Allergy to ASA or Non-Steroidal Anti-Inflammatory drugs
- Syndrome of asthma, rhinitis and nasal polyps
- History of confirmed peptic ulcer or gastrointestinal or severe gynecological bleeding
- General Health Concerns:
- Significant uncontrolled disease of cardiovascular, pulmonary, hepatic, renal, endocrine, rheumatological, neurological, gynecological, or gastrointestinal systems
- Pregnancy or unwillingness to utilize contraception
- History of alcohol or drug abuse within 6 months of screening or current alcohol intake >3 drinks/day
- Laboratory Exclusions (available values obtained within 8 weeks prior to screening visit are acceptable for all except the pregnancy test)
- Positive pregnancy test
- Hemoglobin less than 11.0 g/dL (women) or 13.0 g/dL (men)
- Platelet count < 120, 000/μL
- Serum creatinine level > 1.4 mg/dL (women) or 1.6 mg/dL (men)
- Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) level greater than 2.5 times the upper limit of normal
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether aspirin is effective for treatment of fatigue caused by multiple sclerosis (MS).
Read the detailed description
Fatigue is the most common symptom of multiple sclerosis (MS), affecting up to 90% of people with the disease. MS-related fatigue can be disabling even when other features of MS are mild. It can interfere with physical activity, memory and thinking, social and family activities, and ability to work. Initial treatment consists of energy conservation techniques such as rest periods or naps but when these approaches fail doctors usually recommend a trial of medications. Amantadine, modafinil, and other stimulants are commonly used but help only about half of those who try them. It is unlikely that these drugs directly affect the cause of MS-related fatigue.
It has been difficult to develop new drug therapies for MS-related fatigue because we do not fully understand its causes and do not have precise ways to measure it. We rely on a person's self-report about their fatigue but individuals experience and report fatigue differently. Recent research has shown that some fatigue aspects, such as difficulty maintaining mental concentration ("cognitive fatigue") and physical activity ("motor fatigue"), can be measured more precisely and require further study.
We recently reported results from a study showing that people taking the equivalent of four regular aspirin tablets (1300 mg) daily had reduced MS-related fatigue compared with placebo (sugar pill). The current proposal will attempt to confirm the benefit of aspirin in a larger group of people and to determine if the benefit is related to inflammation. One hundred and thirty-five people with MS-related fatigue will participate at MS clinics at three Mayo Clinic sites. Participants will complete questionnaires that ask about the severity and impact of their fatigue, memory testing to assess cognitive fatigue, and have blood testing to measure markers of inflammation. At the Arizona site, participants will also do strength testing in a motor laboratory to assess motor fatigue. After obtaining two separate baseline evaluations, the participants will be randomly assigned treatment such that one-third will receive 1300 mg per day of aspirin, one-third will receive 162 mg per day of aspirin and one-third will receive a matching placebo. All participants will then return to the clinic on two more occasions over the next eight weeks to repeat the questionnaires, memory and strength testing, blood tests, and report any side-effects. At the end of the study, the results of one of the fatigue questionnaires will be analyzed to determine if aspirin significantly improved fatigue compared with the placebo. The results of other questionnaires and the memory and strength testing will be analyzed as supportive evidence.
If this study is successful, it will provide strong scientific evidence that aspirin helps MS-related fatigue. It will add an important new option for treatment of all MS patients that is also familiar, inexpensive, and has a good long-term safety record. At the same time, it will allow us to better understand the causes of MS-related fatigue and how to measure it more precisely. This information will be extremely useful for development of other therapies in the future.
- Conditions
- Multiple Sclerosis, Fatigue
- Being tested
- High Dose Aspirin (1300 mg/day), Low Dose Aspirin (162 mg/day), Placebo
- Medical subject headings
- Multiple Sclerosis, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Dose Aspirin (1300 mg/day)Drug
Also called acetylsalicylic acid, ASA, Aspirin
1300 milligrams per day (the equivalent of 4 regular aspirin tablets) taken by mouth as two tablets, twice a day in the morning and at noon for 8 weeks
Low Dose Aspirin (162 mg/day)Drug
Also called acetylsalicylic acid, ASA, Aspirin
162 milligrams per day (the equivalent of 2 baby aspirin tablets) taken by mouth as two tablets, twice a day in the morning and at noon for 8 weeks
PlaceboDrug
Placebo tablets matching the active aspirin tablets in appearance, taken as two tablets, twice per day for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| High Dose Aspirin | Active comparator | High Dose Aspirin; 1300 milligrams of aspirin per day, taken by mouth as two tablets, twice per day for 8 weeks Receives: Drug: High Dose Aspirin (1300 mg/day) |
| Low Dose Aspirin | Active comparator | Low Dose Aspirin; 162 milligrams of aspirin per day (the equivalent of 2 baby aspirin tablets) taken by mouth as two tablets, twice a day in the morning and at noon for 8 weeks Receives: Drug: Low Dose Aspirin (162 mg/day) |
| Placebo | Placebo comparator | Placebo tablets, matching the active aspirin tablets in appearance, taken by mouth twice per day for 8 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Fatigue Impact Scale Score
The Modified Fatigue Impact Scale is a list of 21 statements describing how fatigue may affect a person's functioning. Answers ranging from 0 (Never) to 4 (Almost always) were provided by the study subjects for the prior 4 week period. A total score was tallied from a possible 0 (no fatigue impact) to 84 (almost always impacted by fatigue). A lower total score indicates less fatigue-related impact while a higher total score indicates greater fatigue-related impact on a subject's functioning.
Measured: Baseline, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2007 (estimated)
- Study startJul 2007
- Primary completionSep 2013
- Study completionSep 2013
Why it stopped: Interim analysis indicated treatment unlikely effective;slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Responsible party
- Principal investigator, Dean Wingerchuk, Mayo Clinic
- Investigators
- Dean M. Wingerchuk, M.D., MSc, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00467584
- Sponsor's protocol ID
- 06-004850
- Status last verified
- May 2014
- First submitted
- 26 Apr 2007
- Last updated
- 20 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aspirin for Treatment of Multiple Sclerosis-Related Fatigue
- ClinicalTrials.gov ID
- NCT00467584
- Acronym / sponsor ID
- 06-004850
- Conditions
- Multiple Sclerosis, Fatigue
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis indicated treatment unlikely effective;slow recruitment
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Study start
- Jul 2007
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 30 Apr 2007 (estimated)
- Results
- Posted 16 May 2014
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 study is to determine whether aspirin is effective for treatment of fatigue caused by multiple sclerosis (MS).
Detailed description
Fatigue is the most common symptom of multiple sclerosis (MS), affecting up to 90% of people with the disease. MS-related fatigue can be disabling even when other features of MS are mild. It can interfere with physical activity, memory and thinking, social and family activities, and ability to work. Initial treatment consists of energy conservation techniques such as rest periods or naps but when these approaches fail doctors usually recommend a trial of medications. Amantadine, modafinil, and other stimulants are commonly used but help only about half of those who try them. It is unlikely that these drugs directly affect the cause of MS-related fatigue.
It has been difficult to develop new drug therapies for MS-related fatigue because we do not fully understand its causes and do not have precise ways to measure it. We rely on a person's self-report about their fatigue but individuals experience and report fatigue differently. Recent research has shown that some fatigue aspects, such as difficulty maintaining mental concentration ("cognitive fatigue") and physical activity ("motor fatigue"), can be measured more precisely and require further study.
We recently reported results from a study showing that people taking the equivalent of four regular aspirin tablets (1300 mg) daily had reduced MS-related fatigue compared with placebo (sugar pill). The current proposal will attempt to confirm the benefit of aspirin in a larger group of people and to determine if the benefit is related to inflammation. One hundred and thirty-five people with MS-related fatigue will participate at MS clinics at three Mayo Clinic sites. Participants will complete questionnaires that ask about the severity and impact of their fatigue, memory testing to assess cognitive fatigue, and have blood testing to measure markers of inflammation. At the Arizona site, participants will also do strength testing in a motor laboratory to assess motor fatigue. After obtaining two separate baseline evaluations, the participants will be randomly assigned treatment such that one-third will receive 1300 mg per day of aspirin, one-third will receive 162 mg per day of aspirin and one-third will receive a matching placebo. All participants will then return to the clinic on two more occasions over the next eight weeks to repeat the questionnaires, memory and strength testing, blood tests, and report any side-effects. At the end of the study, the results of one of the fatigue questionnaires will be analyzed to determine if aspirin significantly improved fatigue compared with the placebo. The results of other questionnaires and the memory and strength testing will be analyzed as supportive evidence.
If this study is successful, it will provide strong scientific evidence that aspirin helps MS-related fatigue. It will add an important new option for treatment of all MS patients that is also familiar, inexpensive, and has a good long-term safety record. At the same time, it will allow us to better understand the causes of MS-related fatigue and how to measure it more precisely. This information will be extremely useful for development of other therapies in the future.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High Dose Aspirin | Active comparator | Drug: High Dose Aspirin (1300 mg/day)High Dose Aspirin; 1300 milligrams of aspirin per day, taken by mouth as two tablets, twice per day for 8 weeks |
| Low Dose Aspirin | Active comparator | Drug: Low Dose Aspirin (162 mg/day)Low Dose Aspirin; 162 milligrams of aspirin per day (the equivalent of 2 baby aspirin tablets) taken by mouth as two tablets, twice a day in the morning and at noon for 8 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablets, matching the active aspirin tablets in appearance, taken by mouth twice per day for 8 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Confirmed relapsing-remitting or secondary progressive multiple sclerosis,
- Ambulatory for distance of at least 100 meters without gait assistance,
- Persistent fatigue for at least 8 weeks that is not attributable to causes other than MS, and
- Will be able to complete questionnaires and cognitive testing.
Key exclusion criteria (30 listed)
- Other evident causes for fatigue:
- MS Disease Activity and Treatment:
- Current or Recent Fatigue Therapy and Other Medications:
- Medical Contraindications to ASA use:
- General Health Concerns:
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 |
|---|---|---|
| High Dose Aspirin (1300 mg/day)Also: acetylsalicylic acid, ASA, Aspirin1300 milligrams per day (the equivalent of 4 regular aspirin tablets) taken by mouth as two tablets, twice a day in the morning and at noon for 8 weeks | Drug | High Dose Aspirin |
| Low Dose Aspirin (162 mg/day)Also: acetylsalicylic acid, ASA, Aspirin162 milligrams per day (the equivalent of 2 baby aspirin tablets) taken by mouth as two tablets, twice a day in the morning and at noon for 8 weeks | Drug | Low Dose Aspirin |
| PlaceboPlacebo tablets matching the active aspirin tablets in appearance, taken as two tablets, twice per day for 8 weeks | Drug | Placebo |
Primary outcome
Modified Fatigue Impact Scale Score
Time frame: Baseline, 8 weeks
The Modified Fatigue Impact Scale is a list of 21 statements describing how fatigue may affect a person's functioning. Answers ranging from 0 (Never) to 4 (Almost always) were provided by the study subjects for the prior 4 week period. A total score was tallied from a possible 0 (no fatigue impact) to 84 (almost always impacted by fatigue). A lower total score indicates less fatigue-related impact while a higher total score indicates greater fatigue-related impact on a subject's functioning.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Dean M. Wingerchuk, M.D., MSc principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing High Dose Aspirin (1300 mg/day) and Low Dose Aspirin (162 mg/day) in people with Multiple Sclerosis and Fatigue, run by Mayo Clinic at 1 site 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 4 inclusion and 30 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: stopped early, as of the sponsor's last update on 20 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 16 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Modified Fatigue Impact Scale Score (time frame: Baseline, 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 May 2014.