Prophylaxis of Psychiatric Symptoms During Anti-HCV Treatment

Prophylactic Treatment of Peginterferon-associated Psychopathology. A Double-blind Placebo-controlled Trial on the Effects of Escitalopram (Lexapro®) in Patients Treated With Peginterferon and Ribavirin (POPS Study)

The treatment of chronic hepatitis C with peginterferon and ribavirin is highly effective but is hampered by peginterferon-induced psychopathology.

Prevention of peginterferon-induced psychopathology with selective serotonin reuptake inhibitors (SSRI's) (paroxetine) has been shown to be effective in patients treated with interferon for malignant disease. The aim is to study the effects of prophylactic treatment with escitalopram (another SSRI) on peginterferon-associated psychopathology in patients treated with peginterferon and ribavirin for chronic hepatitis C.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Other: Placebo; Drug: Escitalopram

Detailed Description

The treatment of chronic hepatitis C with peginterferon and ribavirin is highly effective but is hampered by peginterferon-induced psychopathology.

Prevention of peginterferon-induced psychopathology with SSRI's (paroxetine) has been shown to be effective in patients treated with interferon for malignant disease. The aim is to study the effects of prophylactic treatment with escitalopram on peginterferon-associated psychopathology in patients treated with peginterferon and ribavirin for chronic hepatitis C.

Design: double blind, randomized controlled trial with two arms, maximum 40 patients per arm. Patients, starting with peginterferon and ribavirin, will be randomized to receive escitalopram therapy 10 mg per day (however, 5 mg in the first two weeks) or placebo.

Study population and selection: eighty patients receiving peginterferon alfa-2a (Pegasys 180 microgram) and ribavirin (Copegus 400 mg twice daily) will be included in the study.

Aims of the study:

1. to asses whether prophylactic treatment with escitalopram avoids significantly the occurrence of peginterferon-induced psychiatric disturbance; defined as an increase of two points on observer-based rating scales reflecting anxiety (BAS:BriefAnxietyScale), loss of concentration, depression and loss of impulse control (Montgomery and Asberg Depression Rating Scale: MADRS), and
2. to assess the frequency of major depression according to DSM IV criteria, in the escitalopram and placebo-treated patients.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1100DD
    • AMC
  • Nijmegen, Netherlands, 6500 HB
    • Radboud University Hospital
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015GD
      • Erasmus MC University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients between 18-70 years of age
• Evidence of chronic hepatitis C by detectable serum HCV-DNA
• Hepatitis C genotype 1,2,3 or 4
• Indication for antiviral therapy of hepatitis C according to current clinical guidelines
• Written informed consent

Exclusion Criteria:

• History or other evidence of severe illness, malignancy or any other condition which would make the patient, in the opinion of the investigator, unsuitable for the study
• Abnormal thyroid stimulating hormone (TSH)
• Presence of contra-indications for antiviral therapy
• Concurrent psychiatric axis I diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria, as the presence of a major depressive episode, bipolar disorder or psychotic disorder.
• Concurrent use of psychotropic drugs such as MAO-inhibitors, St John's wort, Lithium and 5 HT-agonists and antiepileptics.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Other: Placebo
Active Comparator: 1	Drug: Escitalopram; OD 5mg for 2 weeks; OD 10mg for 24 weeks; OD 5mg for 2 weeks; Other Names: Lexapro

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Occurrence of peginterferon-induced psychiatric disturbance

Secondary Outcome Measures

Outcome Measure
Occurrence of major depression

Collaborators and Investigators

• Sponsor: Foundation for Liver Research
• Investigators: Principal Investigator: Robert J De Knegt, MD, Erasmus MC University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: August 22, 2005
• First Submitted That Met QC Criteria: August 22, 2005
• First Posted (Estimate): August 23, 2005

Study Record Updates

• Last Update Posted (Estimate): February 19, 2010
• Last Update Submitted That Met QC Criteria: February 18, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Hepatitis C; Peg-interferon; Psychiatric side-effects
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: HCV05-01