Paroxetine for the Treatment of Interferon Related Side Effects for Hepatitis C
Recruitment status was Active, not recruiting
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 (polyethyline 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- 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.
During the 26 weeks of the paroxetine vs. placebo trial, clinical and laboratory evaluations will be performed on a regular basis with bimonthly visits during the first month of IFN therapy and monthly visits thereafter. Primary outcome variables will be the Montgomery Asberg Depression Rating Scale (MADRS), the Neurotoxicity Rating Scale (NRS), the Clinical Global Impression Score (CGI) the development of major depression (as determined by a semi-structured interview for DSM IV). At the end of the 24th week of sc IFN-alpha plus ribavirin treatment, the randomization code and double-blind will be broken. At this time, patients taking placebo may choose to initiate paroxetine, and patients taking paroxetine may choose to continue treatment until the end of treatment with IFN-alpha (12 months if there has been a positive response to IFN therapy). Patients who meet criteria for major depression during the study and are on the maximal number of pills will be coded (as a major depression), removed from the study and offered open label treatment. If they are on paroxetine, they will be treated with another antidepressant. If they are on placebo, they will be offered treatment with paroxetine. Dosage adjustments of IFN-alpha and ribavirin and monitoring of toxicity of these agents will be managed by a gastroenterologist blinded to the study medication.
Primary Objective: To determine whether 26 weeks of paroxetine treatment will prevent IFN-associated depressive symptoms.
Secondary Objectives: To determine whether 26 weeks of paroxetine treatment will improve compliance and therapeutic efficacy of IFN-alpha. To determine whether 26 weeks of paroxetine will prevent IFN-alpha-associated cognitive dysfunction and other neurotoxicity.
Interferon-Alpha Associated Side Effects
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
|Official Title:||Paroxetine for the Prevention of IFN-Alpha Associated Depression in Patients With Chronic Hepatitis C|