search
Back to results

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

Primary Purpose

Fatigue, Primary Biliary Cirrhosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Modafinil
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fatigue focused on measuring Fatigue

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Sugar Pill

Modafinil

Arm Description

Outcomes

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.

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.

Full Information

First Posted
July 17, 2009
Last Updated
January 13, 2012
Sponsor
Mayo Clinic
Collaborators
American College of Gastroenterology
search

1. Study Identification

Unique Protocol Identification Number
NCT00943176
Brief Title
Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis (PBC)
Acronym
PBC
Official Title
Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Mayo Clinic
Collaborators
American College of Gastroenterology

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fatigue, Primary Biliary Cirrhosis
Keywords
Fatigue

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sugar Pill
Arm Type
Placebo Comparator
Arm Title
Modafinil
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Modafinil
Other Intervention Name(s)
Provigil
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith D Lindor, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27148676
Citation
Silveira MG, Gossard AA, Stahler AC, Jorgensen RA, Petz JL, Ali AH, Lindor KD. A Randomized, Placebo-Controlled Clinical Trial of Efficacy and Safety: Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis. Am J Ther. 2017 Mar/Apr;24(2):e167-e176. doi: 10.1097/MJT.0000000000000387.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs