Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis (PBC) - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	American College of Gastroenterology
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00943176

Purpose

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	Intervention	Phase
Fatigue Primary Biliary Cirrhosis	Drug: Modafinil	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis

Resource links provided by NLM:

Genetics Home Reference related topics: progressive familial intrahepatic cholestasis

MedlinePlus related topics: Cirrhosis

Drug Information available for: Modafinil

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

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. [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: No ]

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. [ Time Frame: after 12 weeks of treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	June 2009
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Sugar Pill: Placebo Comparator	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.
Modafinil: Experimental	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.

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.

Eligibility

Ages Eligible for Study:	21 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943176

Contacts

Contact: Jan L Petz, RN	507-284-3565	jpetz@mayo.edu
Contact: Jill C Keach	507-538-0678	keach.jill@mayo.edu

Locations

United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Jan L Petz, RN 507-284-3565 jpetz@mayo.edu
Principal Investigator: Keith D Lindor, M.D.

Sponsors and Collaborators

Mayo Clinic

American College of Gastroenterology

Investigators

Principal Investigator:

Keith D Lindor, M.D.

Mayo Clinic

More Information

No publications provided

Responsible Party:	Mayo Clinic ( Keith D. Lindor, M.D. / PI )
Study ID Numbers:	08-007692
Study First Received:	July 17, 2009
Last Updated:	July 29, 2009
ClinicalTrials.gov Identifier:	NCT00943176 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Mayo Clinic:

Fatigue

Additional relevant MeSH terms:

Liver Diseases
Fatigue
Fibrosis
Cholestasis
Physiological Effects of Drugs
Central Nervous System Stimulants
Liver Cirrhosis
Protective Agents
Neuroprotective Agents
Pharmacologic Actions

Modafinil
Signs and Symptoms
Cholestasis, Intrahepatic
Digestive System Diseases
Pathologic Processes
Bile Duct Diseases
Therapeutic Uses
Biliary Tract Diseases
Central Nervous System Agents
Liver Cirrhosis, Biliary

ClinicalTrials.gov processed this record on February 08, 2010