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Paroxetine for the Treatment of Interferon Related Side Effects for Hepatitis C

Not Applicable
Completed
Conditions
Hepatitis C
Depression
Interferon-alpha Associated Side Effects
Registration Number
NCT00209118
Lead Sponsor
Emory University
Brief Summary

A.OVERVIEW

This is a 26 week study examining the ability of paroxetine (Paxil) to prevent the development of depression and neurotoxicity in patients receiving either 3 million units of subcutaneous IFN(interferon-alpha-2b) 3 times/week (plus ribavirin, 1000-1200 mg/d)) or PEG (polyethylene glycol) interferon-alpha-2b (1.5 micrograms/kg one time a week) and ribavirin (800 to 1,400 mg a day) for chronic hepatitis C (CHC). The IFN plasma half life (t1/2 of 24 to 34 hours) of PEG, a CHC treatment recently approved by the FDA, is significantly prolonged allowing for once a week dosing. Studies indicate that the side effect profile of the two forms of IFN-alpha treatment are very similar. CHC patients will be screened for study eligibility, and a total of 100 CHC patients between the ages of 18 and 65 years old will be enrolled across three sites (30 at Emory site and a combination of 30 from the University of Pennsylvania, Rush-Presbyterian-Saint Lukes Medical Center in Chicago and Montefiore Medical Center in New York.) Two weeks prior to treatment with subcutaneous IFN-alpha-2b, patients who meet inclusion and exclusion criteria will be stratified on the basis of a history of major depression and then randomly assigned to paroxetine or placebo in double blind fashion.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
Inclusion Criteria
  • age 18-65 years including males, females and minorities
  • serum positive for either anti-HCV antibodies or HCV-RNA positive by PCR
  • compensated liver disease with the following minimum hematologic and biochemical criteria: hemoglobin 3 g/dl for males; 12 g/dl for females, white blood cell count > 3,000/mm3, neutrophil count >1,5000/mm3, platelets > 100,000/mm3, prothrombin time 2 seconds prolonged compared to control, or equivalent INR ratio, albumin stable and within normal limits, serum creatinine within normal limits, thyroid-stimulating hormone (TSH) within normal limits, direct bilirubin 0.3 mg/dl or within 20% of upper limit of normal (ULN) for local laboratory, indirect bilirubin 0.8 mg/dl or within 20% of ULN for local laboratory, fasting blood sugar 115 mg/dl or within 20% of ULN for non-diabetic patients
  • serum hepatitis B surface antigen (HbsAg) negative, antinuclear antibodies (ANA) 1:320
  • normal pre-therapy ocular examination if a history of diabetes or hypertension
  • hemoglobin A1C <8.5% if a history of diabetes
  • negative pregnancy test for women of childbearing potential, and consent to adhere to adequate contraception or monogamous relationship with a male partner who has had a vasectomy during the treatment period and for 6 months after discontinuation of therapy
  • not breast feeding
  • documentation and confirmation of adequate contraception in sexually active males
  • free from all psychotropic medications for a minimum of 14 days prior to baseline visit (8 weeks for fluoxetine)
Exclusion Criteria
  • actively meet criteria for major depression within the past six months
  • active, effective treatment of depression with an antidepressant within the past three months
  • meet criteria for schizophrenia or bipolar disorder (mania) past or present
  • actively meet DSM IV criteria for substance abuse/dependence within the past six months
  • psychotropic medications within 14 days prior to baseline visit (8 weeks for fluoxetine)
  • evidence of untreated or poorly controlled endocrine, cardiovascular, hematological, renal, or neurological disease
  • evidence of decompensated liver disease (such as a history or presence of ascites, bleeding varices, spontaneous encephalopathy)
  • history of CNS trauma or active seizure disorder requiring medication
  • any cause for liver disease other than chronic hepatitis C, such as co-infection with hepatitis B virus and/or human immunodeficiency virus, hemochromatosis, or Wilson's disease
  • prior treatment with other (other than IFN-alpha or ribavirin) immunomodulatory drugs, including corticosteroids within 6 months of entry into protocol
  • clinical gout
  • known hypersensitivity to alpha interferon or ribavirin
  • hemoglobinopathies (e.g. thalassemia)
  • a positive pregnancy test
  • clinically significant retinal abnormalities
  • organ transplants
  • a score of <24 on the Mini Mental Status Exam (MMSE)
  • prior history of severe adverse events associated with paroxetine
  • any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Depressive Symptom Scores
Development of Major Depression
Secondary Outcome Measures
NameTimeMethod
neurotoxicity
dosage reduction
discontinuation
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