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

Last updated: April 7, 2016
Sponsor: Emory University
Overall Status: Completed

Phase

N/A

Condition

Hepatitis

Depression

Liver Disorders

Treatment

N/A

Clinical Study ID

NCT00209118
0112-1998
  • Ages 18-65
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 biochemicalcriteria: 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 2seconds prolonged compared to control, or equivalent INR ratio, albumin stable andwithin normal limits, serum creatinine within normal limits, thyroid-stimulatinghormone (TSH) within normal limits, direct bilirubin 0.3 mg/dl or within 20% of upperlimit 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 fornon-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 toadequate contraception or monogamous relationship with a male partner who has had avasectomy during the treatment period and for 6 months after discontinuation oftherapy

  • 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 baselinevisit (8 weeks for fluoxetine)

Exclusion

Exclusion Criteria:

  • actively meet criteria for major depression within the past six months

  • active, effective treatment of depression with an antidepressant within the past threemonths

  • meet criteria for schizophrenia or bipolar disorder (mania) past or present

  • actively meet DSM IV criteria for substance abuse/dependence within the past sixmonths

  • psychotropic medications within 14 days prior to baseline visit (8 weeks forfluoxetine)

  • 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 withhepatitis B virus and/or human immunodeficiency virus, hemochromatosis, or Wilson'sdisease

  • 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 patientunsuitable for enrollment, or could interfere with participating in or completing theprotocol

Study Design

Total Participants: 60
Study Start date:
Estimated Completion Date:
July 31, 2005