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

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00943176

Collaborator

American College of Gastroenterology (Other)

Enrollment

Location

Arms

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Fatigue Primary Biliary Cirrhosis	Drug: Modafinil	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sugar Pill	Drug: Modafinil 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. Other Names: Provigil
Experimental: Modafinil	Drug: Modafinil 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. Other Names: Provigil

Arm

Intervention/Treatment

Placebo Comparator: Sugar Pill

Drug: Modafinil

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.

Other Names:

Provigil

Experimental: Modafinil

Drug: Modafinil

Other Names:

Provigil

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.