Fatigue
Conditions
Keywords
Fatigue, low energy, ALS, treatment
Brief summary
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
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.
Interventions
DRUGModafinil
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.
DRUGPlacebo
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.
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Considered Responders (Scored 1 or 2) on Clinical Global Impressions Scale | 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Impaired Scores on Neuropsychological (Brief) Test Battery | 4 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
dates of recruitment were June 2006 through October 2007 at at the MDA-ALS Neurology Clinic at Columbia University.
Pre-assignment details
Medical exclusion criteria were low thyroid levels which led to 3 patients excluded.
Participants by arm
| Arm | Count |
|---|---|
| Modafinil 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. | 25 |
| Placebo 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. | 7 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Burden of travel | 1 | 0 |
Baseline characteristics
| Characteristic | Modafinil | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 6 Participants | 29 Participants |
| Age Continuous | 59 years STANDARD_DEVIATION 13 | 56 years STANDARD_DEVIATION 5 | 58 years STANDARD_DEVIATION 12 |
| Fatigue Severity Scale score >40 | 25 participants | 7 participants | 32 participants |
| Region of Enrollment United States | 25 participants | 7 participants | 32 participants |
| Sex: Female, Male Female | 11 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 7 |
| serious Total, serious adverse events | 0 / 25 | 0 / 7 |
Outcome results
Primary
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.
Time frame: 4 weeks
Population: Analysis was Intention to Treat (ITT) including Last-Observation-Carried-Forward (LOCF) as indicated. Proof of concept study so N was based on accrual feasibility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Modafinil | Participants Considered Responders (Scored 1 or 2) on Clinical Global Impressions Scale | 19 participants considered responders |
| Placebo | Participants Considered Responders (Scored 1 or 2) on Clinical Global Impressions Scale | 1 participants considered responders |
Secondary
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.
Time frame: 4 weeks