Modafinil to Treat Fatigue in Post-Polio Syndrome
Modafinil to Treat Fatigue in Post-Polio Syndrome
This study, conducted at the Walter Reed Army Medical Center, the National Rehabilitation
 Hospital, and the National Institutes of Health, will examine whether the drug Modafinil can
 decrease fatigue in patients with post-polio syndrome. Many people who have had polio develop
 weakness and severe fatigue several years after their recovery from the acute disease.
 Modafinil is approved by the Food and Drug Administration to improve wakefulness in patients
 with narcolepsy (disease in which patients have excessive daytime sleepiness) and has been
 used to treat patients with fatigue related to other medical conditions, such as multiple
 sclerosis. This study will compare the effects of two doses of Modafinil and of a placebo (a
 pill with no active ingredient) on fatigue in patients with post-polio syndrome.

 Patients who develop fatigue, weakness, muscle pain or atrophy, and functional loss at least
 15 years after recovering from polio and whose symptoms cannot be attributed to another cause
 may be eligible for this study. Candidates will be screened with a medical history, physical
 and neurological examinations, fatigue rating scales, electrocardiogram, blood and urine
 tests, drowsiness and depression evaluations, and an electroymogram (EMG) to diagnose nerve
 or muscle problems. For the EMG, electrodes (small metal discs) are taped to the skin and a
 needle is inserted into a muscle to record the electrical activity.

 Candidates will also undergo a sleep study to exclude abnormal sleep patterns as the cause of
 the fatigue. For this study, patients stay overnight at the NIH hospital. Electrodes are
 placed on the throat, on a finger, and on the chest (for an electrocardiogram), and a
 respiratory belt is placed around the chest-abdomen area. During sleep (from 10:30 p.m. to 6
 a.m.), brain waves, eye and leg movements, muscle tone, respiration, and heart rate are
 recorded. Beginning at 8 a.m. the following morning, the patient takes 20-minute naps to
 measure the level of daytime sleepiness, using a recording technique similar to that of the
 all-night study. When five naps are completed, the sleep study ends. Candidates may also
 undergo a lumbar puncture (spinal tap) to check for certain chemicals in the spinal fluid
 that might be related to fatigue and to look for possible causes of post-polio syndrome. This
 procedure is optional. For the lumbar puncture, a local anesthetic is given and a needle is
 inserted in the space between the bones in the lower back where the cerebrospinal fluid
 circulates below the spinal cord. A small amount of fluid is collected through the needle.

 Patients enrolled in the study will complete a sleep diary during the entire study period.
 They will be randomly assigned to one of two treatment groups-Modafinil or placebo-for 6
 weeks, followed by a 2-week washout period with no medication, and then a crossover phase, in
 which patients who took Modafinil for the first 6 weeks now take placebo, and those who took
 placebo now take Modafinil.

 At the first study visit, patients will be given a supply of study medication and have blood
 drawn. They will take one pill twice a day during both study phases. In both study phases,
 evaluations will be done 3 and 6 weeks after starting the medication. The evaluations include
 filling out the same forms completed at the screening visit, a review of drug side effects,
 and a review of medical problems since the last study visit. At the 6-week visit, blood is
 also drawn.
The main objective of this study is to determine if the drug Modafinil is effective in the
 treatment of fatigue in patients with post-polio syndrome (PPS). PPS is a motor neuron
 disease experience by more than 400,000 Americans, characterized by new weakness and intense
 fatigue. The cause of fatigue, the most common and disabiling symptom in these patients, is
 unknown and there is no effective treatment. In the present study, selected PPS patients will
 be randomized to receive two different doses of Modafinil or placebo. After six weeks, the
 patients will enter a two-week wash out period, and then will be crossed over to the other
 arm. The sample size has been powered to reflect a significant difference in the scales of
 fatigue. Secondary exploratory studies will include investigation of sleep patterns as a
 cause contributing to fatigue and a search for upregulation of fatigue-associated cytokines
 in the patient's serum and CSF.
-  INCLUSION CRITERIA:

 Patients will have to meet the clinical criteria for the diagnosis of PPS, have fatigue as
 a major complaint, and be 18 years or older, of either sex.

 EXCLUSION CRITERIA:

 Sensitivity to modafinil.

 A score of 34 or below on the FSS.

 Suffer from depression (BDI-II score of 31 or higher) severe enough to compound the fatigue
 evaluation.

 Another general medical condition that might produce fatigue to a sufficient degree to
 compound and confuse the assessment of fatigue due to PPS.

 Use of a drug known to cause a clinically significant interaction with modafinil.

 Presence of sleep disorder suggested by Epworth Sleepiness Scale (score of 18 or higher),
 patient history, sleep diary or polysomnogram.

 Pregnancy .

 Breastfeeding.