Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis (PBC)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the use of modafinil in the treatment of fatigue in patients with Primary Biliary Cirrhosis. The general aim of the study is to identify a safe and effective therapy for fatigue in patients with primary biliary cirrhosis.

Detailed Description
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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.

Official Title
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Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis

Conditions
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Fatigue, Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Modafinil


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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 |
| --- | --- |
| Placebo Comparator: Sugar Pill<br> | Drug: Modafinil<br>* 100 mg tablets of modafinil or matched placebo will be given for a total of 12 weeks. Patients will be instructed to start one capsule once daily (modafinil or placebo), and dose will be titrated according to tolerability and response.<br>* Other names: Provigil;|
| Experimental: Modafinil<br> | Drug: Modafinil<br>* 100 mg tablets of modafinil or matched placebo will be given for a total of 12 weeks. Patients will be instructed to start one capsule once daily (modafinil or placebo), and dose will be titrated according to tolerability and response.<br>* Other names: Provigil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main endpoint will be the change in fatigue severity (quantified by the FFSS) following 12 weeks of treatment, compared to baseline values. |  | after 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcome includes frequency of adverse events, change in alkaline phosphatase, AST, total bilirubin and albumin levels after 12 weeks of therapy compared to baseline values, change in fatigue severity compared to baseline. |  | after 12 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fatigue