Aspirin as a Pre-Treatment for Exercise in Multiple Sclerosis

NCT03051646 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: AAAQ1758
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Exercise has many benefits for people with multiple sclerosis (MS), such as improved physical symptoms, mood, fatigue, and cognition. However, many people with MS refrain from exercising because of the discomfort of exhaustion and overheating that they experience. This study investigates the use of aspirin before exercise as a treatment to reduce overheating and exhaustion, thereby availing many more people with MS the opportunity to benefit from exercise. The investigators recently published the first-ever report of elevated body temperature in relapsing-remitting MS (RRMS) patients relative to healthy controls, and elevated temperature was linked to worse fatigue. This finding that body temperature is elevated and linked to fatigue in RRMS lays the groundwork for a paradigm shift in our understanding and treatment of fatigue. That is, the focus shifts from exogenous to endogenous temperature, and from stimulant medication to cooling treatments. A recent study comparing healthy adults to adults with MS showed that whereas exercise increased body temperature in both groups, only in the MS group was it correlated with exhaustion. The reason for this may relate to the elevation in resting body temperature in relapsing-remitting MS (RRMS) patients relative to healthy controls. The finding is clinically meaningful, as elevated body temperature was correlated with worse fatigue in patients. Exercise Aim: To determine whether pretreatment with ASA (compared to placebo: within subject crossover design) before exercise results in improved exercise performance (i.e., increased time-to-exhaustion). The investigators hypothesize that participants will tolerate exercise for longer after taking ASA than placebo. This hypothesis is based on a) demonstrated efficacy of antipyretic for reducing body temperature during exercise in healthy controls, b) demonstrated efficacy of antipyretic for reducing fatigue in non-exercising MS patients, and c) demonstrated efficacy of elaborate (unblinded) cooling treatments (e.g., cooling garments, cooling hand chamber) for improving exercise performance in MS patients. Note that this project is especially important for MS patients, who have a disease-specific body temperature elevation and sensitivity to heat (i.e., Uhthoff's).

Conditions

Fatigue; Overheating

Keywords

Exercise; Time to Exhaustion

Outcome Measures

Primary Outcomes (1)

• Change in Time to Exhaustion

  The measure of interest is the length of time (in seconds) spent exercising at each session. This time has no pre-set upper limit, i.e. patients are free to exercise as long as they wish. This means that the time will not be censored. However, please note that healthy adults' time to exhaustion is approximately 12 minutes.

  ASA's effect will be assessed from date of randomization until cessation of exercise test at each of two study visits to be completed within a 14-day period.

Secondary Outcomes (1)

• Exercise-induced Body Temperature Increase

  Effect of treatment on body temperature in a single session (i.e., pre- to post- exercise test) to be completed within a 14-day period

Study Arms (2)

Acetylsalicylic acid first, placebo second

EXPERIMENTAL

Participant is administered acetylsalicylic acid one hour prior to exercise.

Drug: Acetylsalicylic acid at 1st visit, then Placebo at 2nd visit

Placebo oral capsule first, ASA second

PLACEBO COMPARATOR

Participant is administered placebo one hour prior to exercise.

Drug: Placebo at 1st visit, then Acetylsalicylic acid at 2nd visit

Interventions

Acetylsalicylic acid at 1st visit, then Placebo at 2nd visit DRUG

650 mg dose of acetylsalicylic acid is administered in a capsule one hour prior to exercise; Placebo oral capsule is administered one hour prior to exercise

Also known as: aspirin, placebo

Acetylsalicylic acid first, placebo second

Placebo at 1st visit, then Acetylsalicylic acid at 2nd visit DRUG

Placebo oral capsule is administered one hour prior to exercise; 650 mg dose of acetylsalicylic acid is administered in a capsule one hour prior to exercise

Also known as: placebo, aspirin

Placebo oral capsule first, ASA second

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• RRMS
• self report of overheating during exercise
• low physical disability (EDSS total score 4.5 or less); fully ambulatory without aid
• exacerbation-free (and no use of corticosteroids) for 6 weeks prior
• BMI 35 or lower

You may not qualify if:

• uncontrolled hypertension or vascular disease of the legs
• current medications for heart or blood pressure problem
• prior history of head injury, stroke, or other neurological disease/disorder
• currently taking antipyretics or pain medication daily
• presence of major depressive disorder or other psychiatric diagnosis
• formally diagnosed sleep disorder
• pulmonary disease, heart disease or other heart problem
• diabetes mellitus or problem with blood sugar levels
• lower body weakness or reliance on supportive devices for walking (as indicated through EDSS)
• counter indications to aspirin use: history of confirmed peptic ulcer, gastrointestinal or sever gynecological bleeding; tarry stool or fecal occult blood; syndrome of asthma, rhinitis or nasal polyps

Sponsors & Collaborators

• Columbia University: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

Columbia University Medical Center, MS Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Fatigue; Sunstroke; Motor Activity

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stroke; Heat Stress Disorders; Wounds and Injuries; Behavior

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Small planned sample size in this pilot warrants follow-up replication in larger sample.

Results Point of Contact

• Title: Victoria M. Leavitt
• Organization: Columbia University Medical Center

vl2337@cumc.columbia.edu

212 342 1351

Study Officials

• Victoria Leavitt, PhD

  Assistant Professor of Neuropsychology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Blinding will be overseen by the CUMC pharmacy; randomization schedule will be submitted to the pharmacy by a third party who is not involved in the study (i.e., non-study personnel). Study investigators will remain blinded until data collection is complete and data have been analyzed.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neuropsychology

Model Details: Design is a within-subject crossover placebo-controlled experiment. Each participant will be seen for two exercise sessions (stationary cycling) on two days separated by one week, and will receive either ASA or placebo (treatment) at each session prior to commencing exercise. Order of treatment will be randomized and counter-balanced. As such, each participant will serve as his/her own control.

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 14, 2017
• Study Start: January 13, 2017
• Primary Completion: May 10, 2017
• Study Completion: May 10, 2017
• Last Updated: November 20, 2018
• Results First Posted: November 20, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)