The general aim of the study is to identify a safe and effective therapy for fatigue in patients with primary biliary cirrhosis. Specific aims include: 1) to determine the safety profile of modafinil in patients with primary biliary cirrhosis; 2) to evaluate the beneficial effects of modafinil on patients with primary biliary cirrhosis and fatigue as documented by a well-validated questionnaire (Fisk Fatigue Severity Score) to be applied at the beginning and end of the study period; and 3) to compare the performance of three questionnaires (Fisk Fatigue Severity Score, Fatigue Severity Scale and the fatigue domain of the PBC-40) as instruments to determine the benefits of a therapeutic intervention on fatigue by establishing the minimally important clinical difference of these measures of fatigue.
Inclusion Criteria:
- Primary biliary cirrhosis will be defined as present when 2 of 3 of the following criteria are met:
- Chronic cholestatic liver disease for greater than 6 months with alkaline phosphatase levels greater than 1.5 times the upper limit of normal prior to UDCA treatment.
- Positive AMA titer greater or equal to 1:40 or AMA greater than 0.1U. Liver histology in the past with features consistent with or diagnostic of PBC.
- A previous ultrasound, computed tomography (CT), or cholangiography of the biliary tree excludes biliary obstruction.
- Verbal report of fatigue for greater than 6 months.
Exclusion Criteria:
- Patients with other serious coexistent conditions such as pre-existing advanced malignancy or severe cardiopulmonary disease which would be expected to limit their expectancy to less than three years.
- Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis or sclerosing cholangitis.
- Treatment of underlying PBC has been modified in the preceding six months.
- Anticipated need for transplantation in one year (Mayo survival model <80% one-year survival without transplant) or MELD above 15.
- Recurrent variceal bleeding, presence of diuretic-resistant ascites, or spontaneous encephalopathy.
- Active drug or alcohol use.
- History of drug and/or stimulant (e.g. methylphenidate, amphetamine, or cocaine) abuse.
- Serum bilirubin >4 mg/dl.
- Serum creatinine over 1.4 mg/dl.
- Pregnancy.
- Breast-feeding.
- Inability or unwillingness to practice contraceptive measures for the prevention of pregnancy if appropriate.
- Other fatigue related diagnoses such as anemia, thyroid disease, renal failure, use of beta-blockers and untreated depression.
- Known hypersensitivity to modafinil.
- Uncontrolled hypertension.
- Patients with hypertension and left ventricular hypertrophy documented on ECG in the last 2 years.
- Recent (<6 months) history of myocardial infarction or unstable angina.
- Patients with history of psychosis.
- Patients receiving cyclosporine, warfarin, tricyclic agents, carbamazepine, phenobarbital, rifampin, ketoconazole or itraconazole in the last 3 months.
Should you decide to participate you will be put in one or two groups by chance (as in the flip of a coin). One group will receive modafinil (active medication) and one group will receive placebo (no active medication or "sugar pills"). Neither you, the study doctor, or other study personnel will know which group you are in. You will take the pills for 12 weeks. You will receive phone calls while you are in the study, asking how you are doing. Blood draws will be done twice during the study: at the time you join the study and when the study comes to an end (12 weeks later), you will be asked to complete 3 questionnaires with questions related to your symptoms and quality of life at the time you join the study and then again when the study is complete.
12 weeks
Last updated: 01/13/2012
NCT ID: NCT00943176
IRB Number:08-007692
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