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

Fatigue Clinical Trial

— PBC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00943176
• Other study ID #: 08-007692
• Status: Completed
• Phase: Phase 1
• First received: July 17, 2009
• Last updated: January 13, 2012
• Start date: June 2009
• Est. completion date: April 2011

Study information

• Verified date: January 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatigue
• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

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.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	American College of Gastroenterology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes