Wise Young
04-16-2002, 08:36 PM
[S62.003] Aspirin for Multiple Sclerosis-Related Fatigue: Results of a Double-Blind Placebo-Controlled Study
Dean M. Wingerchuk, Eduardo E. Benarroch, Peter C. O'Brien, B. Mark Keegan, Claudia F. Lucchinetti, John H. Noseworthy, Brian G. Weinshenker, Moses RodriguezÂ*Scottsdale, AZ; Rochester, MN
OBJECTIVE: To determine whether aspirin (ASA) reduces the severity of multiple sclerosis-related fatigue.
BACKGROUND: Fatigue is the most common symptom of multiple sclerosis (MS) and often the most disabling early in the disease course. Several lines of clinical evidence suggest it is related to the underlying immunopathogenesis of the disease. Pharmacotherapy is currently limited to amantadine and nonspecific central nervous system stimulants that provide little insight into fatigue pathophysiology and are modestly effective for most patients. More effective and targeted therapies are urgently needed.
Following previous clinical observations, we had anecdotal success empirically treating MS fatigue with 650-1900 mg/d of ASA. We performed a randomized, controlled study to objectively evaluate the effects of ASA on MS-related fatigue.
DESIGN/METHODS: Thirty ambulatory patients with significant MS-related fatigue (MS-specific Fatigue Scale score4) of at least 3 months duration were enrolled in this double-blind, placebo-controlled, crossover trial. Patients with clinically significant depression, medical contraindications, or who were using current MS-fatigue therapies were excluded. During the first 6-week phase of the study, 15 patients were randomized to receive 650 mg ASA twice per day (morning and noon) and 15 were randomized to placebo. Following a 2-week washout period, patients crossed over to the other treatment for 6 weeks. Fatigue was measured using descriptive (patient report of clinical change) and continuous measures (visual analog scale, modified and complete forms of the Fatigue Impact Scale, Fatigue Severity Scale, MS-Specific Fatigue Scale). Statistical analysis was performed using McNemar and paired t-tests as appropriate.
RESULTS: Twenty-four women and six men were enrolled. The mean Expanded Disability Status Scale (EDSS) score was 2.5 (range 0-5.5) and mean fatigue duration was 33 months. Twenty-six patients completed the study. Forty-two percent of patients reported good or excellent improvement in fatigue levels during ASA treatment compared with 11% during the placebo phase (p=0.008). Modified Fatigue Impact Scale scores were also significantly reduced (p=0.035). There were trends toward benefit on all measurement scales. Patient questionnaires indicated that treatment blinding was successfully maintained and there were no significant adverse events.
CONCLUSIONS: ASA may reduce fatigue severity in MS. The results of this controlled study strengthen the concept of MS-related fatigue as an immunologically mediated construct and theoretically implicate several pathophysiological mechanisms involving prostaglandins, cytokines, and the neuroendocrine axis in fatigue generation. Further study is warranted to confirm these results and to explore the mechanisms by which ASA modulates fatigue.
Supported By: Mayo Clinic and Foundation
Category - MS and Related Diseases
SubCategory - Therapeutic Trials
Dean M. Wingerchuk, Eduardo E. Benarroch, Peter C. O'Brien, B. Mark Keegan, Claudia F. Lucchinetti, John H. Noseworthy, Brian G. Weinshenker, Moses RodriguezÂ*Scottsdale, AZ; Rochester, MN
OBJECTIVE: To determine whether aspirin (ASA) reduces the severity of multiple sclerosis-related fatigue.
BACKGROUND: Fatigue is the most common symptom of multiple sclerosis (MS) and often the most disabling early in the disease course. Several lines of clinical evidence suggest it is related to the underlying immunopathogenesis of the disease. Pharmacotherapy is currently limited to amantadine and nonspecific central nervous system stimulants that provide little insight into fatigue pathophysiology and are modestly effective for most patients. More effective and targeted therapies are urgently needed.
Following previous clinical observations, we had anecdotal success empirically treating MS fatigue with 650-1900 mg/d of ASA. We performed a randomized, controlled study to objectively evaluate the effects of ASA on MS-related fatigue.
DESIGN/METHODS: Thirty ambulatory patients with significant MS-related fatigue (MS-specific Fatigue Scale score4) of at least 3 months duration were enrolled in this double-blind, placebo-controlled, crossover trial. Patients with clinically significant depression, medical contraindications, or who were using current MS-fatigue therapies were excluded. During the first 6-week phase of the study, 15 patients were randomized to receive 650 mg ASA twice per day (morning and noon) and 15 were randomized to placebo. Following a 2-week washout period, patients crossed over to the other treatment for 6 weeks. Fatigue was measured using descriptive (patient report of clinical change) and continuous measures (visual analog scale, modified and complete forms of the Fatigue Impact Scale, Fatigue Severity Scale, MS-Specific Fatigue Scale). Statistical analysis was performed using McNemar and paired t-tests as appropriate.
RESULTS: Twenty-four women and six men were enrolled. The mean Expanded Disability Status Scale (EDSS) score was 2.5 (range 0-5.5) and mean fatigue duration was 33 months. Twenty-six patients completed the study. Forty-two percent of patients reported good or excellent improvement in fatigue levels during ASA treatment compared with 11% during the placebo phase (p=0.008). Modified Fatigue Impact Scale scores were also significantly reduced (p=0.035). There were trends toward benefit on all measurement scales. Patient questionnaires indicated that treatment blinding was successfully maintained and there were no significant adverse events.
CONCLUSIONS: ASA may reduce fatigue severity in MS. The results of this controlled study strengthen the concept of MS-related fatigue as an immunologically mediated construct and theoretically implicate several pathophysiological mechanisms involving prostaglandins, cytokines, and the neuroendocrine axis in fatigue generation. Further study is warranted to confirm these results and to explore the mechanisms by which ASA modulates fatigue.
Supported By: Mayo Clinic and Foundation
Category - MS and Related Diseases
SubCategory - Therapeutic Trials