Modafinil for Treatment of Fatigue in ALS Patients

Study Overview
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Brief Summary
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The purpose of this pilot study is to evaluate whether modafinil is helpful in alleviating fatigue, low energy, drowsiness and difficulty concentrating among patients with amyotrophic lateral sclerosis (ALS), and to evaluate incidence and frequency of adverse events, if any.

Detailed Description
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ALS is an untreatable, progressive, fatal neurodegenerative disease whose etiology is unknown and whose course is relatively rapid (median survival 3 years after diagnosis). Palliative care, including symptom management, can contribute greatly to improved quality of life. In this context, alleviation of fatigue can help maintain function, extend the duration of time when employment is feasible for those still working, and can enable patients to more fully participate in and enjoy social and recreational activities. Given the prevalence of fatigue in this population, identification of effective treatment is a meaningful goal.

Official Title
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Modafinil for Treatment of Fatigue in ALS Patients: Pilot Study

Conditions
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Fatigue

Intervention / Treatment
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* Drug: Modafinil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of ALS Ages 18-80 Clinically significant fatigue (4.5+ on Fatigue Severity Scale with duration 3+ months plus impairment in 1+ categories of role function) Speaks English Able and willing to give informed consent Can communicate verbally or with assistive device Can swallow capsules Forced vital capacity 50+% Exclusion Criteria: Untreated hypothyroidism (TSH > 4.25 UIU/ML) Untreated and uncontrolled hypertension Clinically significant anemia (HCT < 33%) Untreated or under-treated major depressive disorder Current clinically significant suicidal ideation Started antidepressant medication for treatment of depression during past 6 weeks Currently taking psychostimulant medication History or current psychosis or bipolar disorder Fecund women not currently using barrier methods of contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modafinil<br>Eligible patients will be treated at baseline through Week 4. Those who choose to continue will have additional in-person visits at Weeks 8 and 12 visits (and Week 16 for those starting modafinil at Week 4). | Drug: Modafinil<br>* Dose schedule: 50 mg/day for 1 week, increasing to 100 mg/day at Week 2. Thereafter, dose may be increased to 300 mg/day as clinically indicated, in the absence of dose-limiting side effects. Dose is daily, in A.M., for 4 weeks.<br>* Other names: Provigil;|
| Placebo Comparator: Placebo<br>Sugar pill equivalent to the active comparator. Dosing schedule will be the same as the dosing schedule for Modafinil. | Drug: Placebo<br>* Placebo capsules are administered on the same schedule as active drug: 50 mg/day for 1 week, increasing to 100 mg/day at Week 2. Thereafter, dose may be increased to 300 mg/day in the absence of clinical improvement and dose limiting side effects. Dose is daily, in A.M.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants Considered Responders (Scored 1 or 2) on Clinical Global Impressions Scale | The CGI is a standardized assessment tool widely used in clinical psychopharmacology trials as an outcome measure. Scores range from 1= very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5-7 = worse. We use it as a dichotomous measure with scores of 1 or 2 signifying responder and all the rest as non-responder using all available data including clinician judgement, and ratings scales. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Impaired Scores on Neuropsychological (Brief) Test Battery | This was an initial plan but the large majority of patients were too impaired (either anarthric or unable to use hands) to complete the tests we had selected so this outcome measure turned out to be unfeasible. Therefore, 0 participants were analyzed. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fatigue, low energy, ALS, treatment