Trial of Citalopram for the Prevention of Depression (PICCO)

May 19, 2017 updated by: Marina Klein

A Randomized, Placebo Controlled Trial of Citalopram for the Prevention of Depression and Its Consequences in HIV-Hepatitis C Co-infected Individuals Initiating Pegylated Interferon/Ribavirin Therapy

With the improved prognosis of human immunodeficiency virus (HIV) infection, end stage liver disease due to hepatitis C (HCV) now represents a major cause of morbidity and mortality in people with HIV. Treatment for HCV has become increasingly important as a means of preventing the consequences of chronic HCV infection. Paradoxically, co-infected patients have low rates of treatment initiation and completion in large part because they have a high risk of developing neuropsychiatric symptoms while receiving PEG-interferon (PEG-IFN). There are a large number of co-infected individuals in Canada who could benefit from HCV therapy if tolerability could be improved. This trial will address whether prophylactic use of antidepressants in HIV-HCV infected patients initiating HCV therapy can prevent the development of neuropsychiatric side effects and thus permit more patients to receive full treatment for HCV.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Trial design:

This study is a Canadian multicentre randomized, double-blind placebo controlled trial. We will evaluate whether prophylactic citalopram compared to symptomatic treatment of depression can significantly increase the amount of HCV therapy received in co-infected patients during the first 24 weeks. Post study follow-up will extend until 6 months after cessation of HCV therapy (up to 72 weeks) to capture information on SVR (sustained virologic response) for HCV. 76 patients will be randomized in a 1:1 ratio to citalopram or placebo. Patients will be stratified by study centre and HCV genotype. Citalopram (or placebo) will begin 3 weeks before HCV treatment at an initial dose of 10 mg per day then be increased to 20 mg per day after one week and continued throughout treatment with PEG-IFN/ribavirin (up to 48 weeks) and then tapered to discontinuation at completion of HCV therapy. The management of depression emerging in study participants is mandated in the protocol to ensure that the original treatment assignments remain blinded while allowing for all subjects to remain in the study and mimics what would take place in clinical practice.

Analysis:

The analyses will follow the intention-to-treat approach. Random regression modelling will be employed to analyse longitudinal data on adherence to prescribed PEG-IFN and ribavirin dosage at weeks 12 and 24. Survival analyses will be used to compare the two treatment groups with respect to the time to the development of depressions.

Implications:

Prophylactic antidepressants may not only prevent overt depression but may also diminish the development of sub-clinical depressed mood. Effective prevention of a broad range of neuropsychiatric symptoms by use of citalopram has the potential to diminish morbidity associated with PEG-IFN treatment and consequently allow a greater number of patients to complete full therapy. In addition, such an approach may help patients remain adherent to their HIV therapy during the course of HCV treatment which could have long-term personal and public health implications by preventing the emergence of HIV resistance. Furthermore, if shown to be an effective strategy for preventing neuropsychiatric symptoms, treatment for HCV may become more accessible to the large number of patients who may not have ready access to the frequent and intensive psychiatric monitoring, necessary for the early detection and treatment of depression that manifests on PEG-IFN.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H2X 2P4
        • Immunodeficiency Service Montreal Chest Institute McGill University Health Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • HIV+ adults with chronic HCV infection requiring therapy and with no contraindications to PEG-IFN/ribavirin will be enrolled.

Exclusion Criteria:

  • Subjects with prior suicide attempt, active depression, treatment with antidepressants within 6 months of study entry or with other psychiatric disorders will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo + PEG-interferon-alfa2b + ribavirin
Drug: Placebos
Experimental: Citalopram
Citalopram + PEG-interferon-alpha2b + ribavirin
Drug: Citalopram

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary outcome is the average proportion of PEG-IFN and ribavirin doses received in participants receiving citalopram compared with placebo
Time Frame: week 24
week 24
A second major objective is to compare arms with respect to the rate of moderate-to-severe depressive symptoms during the first 24 weeks of therapy.
Time Frame: week 12 and week 24
week 12 and week 24

Secondary Outcome Measures

Outcome Measure
Time Frame
Secondary measures will assess impact of citalopram versus placebo on anxiety, neurocognitive function, quality of life and adherence to therapy. HCV and HIV control will also be examined.
Time Frame: 24 weeks
24 weeks
Substudies aimed at understanding the pathogenesis of neuropsychiatric side effects and neurocognitive function in this population will be performed.
Time Frame: 24 weeks
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Marina Klein

Collaborators

Schering-Plough
Ontario HIV Treatment Network
CIHR Canadian HIV Trials Network

Investigators

  • Principal Investigator: Marina B Klein, MD, Immunodeficiency Service Montreal Chest Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

April 21, 2006

First Submitted That Met QC Criteria

April 21, 2006

First Posted (Estimate)

April 25, 2006

Study Record Updates

Last Update Posted (Actual)

May 22, 2017

Last Update Submitted That Met QC Criteria

May 19, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTN194
  • Schering #2229

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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