Efficacy and Safety of Escitalopram for Prevention of Depression Induced by Peg-Interferon in Hepatitis C Patients

August 5, 2020 updated by: Germans Trias i Pujol Hospital

Study of the Efficacy and Safety of Escitalopram for the Prevention of Depressive Episodes Induced by Peg-Interferon Alpha2a and Ribavirin in Chronic Hepatitis C Patients. Randomized, Double-Blind, Placebo-Controlled Clinical Trial

The purpose of this study is to determine whether the use of an antidepressant (escitalopram) can prevent depressive episodes that appear during the treatment with peg-interferon and ribavirin in patients with chronic hepatitis C.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Chronic hepatitis C is a prevalent condition, and the main cause of chronic liver diseases, including cirrhosis and cancer. Nowadays, interferon-alfa in combination with ribavirin is the main treatment option for this condition. In the last years, interferon molecule has been modified in order to improve tolerance into pegylated interferon.

Interferon-alfa has been associated with a high prevalence of psychiatric side effects, especially major depression (up to 25% of the cases), which is one of the main concerns about using this treatment. In fact, major depression is one of the main reasons of treatment withdrawal and treatment failure.

Major depression induced by interferon-alfa can be successfully treated with antidepressants, but we don't know if antidepressants can also prevent the development of major depression, and if this can be a safe intervention. In the literature, there is only one controlled trial about this issue, in cancer patients, and some open studies in hepatitis C.

In order to evaluate the efficacy, and safety, of an antidepressant (escitalopram) for preventing peginterferon's induced depressive episodes in patients with chronic hepatitis C, we have designed this 14-weeks placebo-controlled, double-blind, randomized clinical trial. Study interventions will be started two weeks before peginterferon + ribavirin's treatment onset.

Subjects included in the study will be patients with chronic hepatitis C who are going to be treated with peginterferon-alfa2a + ribavirin, and without mental disorders requiring active psychotropic treatment.

The main variables studied will be the appearance of a major depressive episode, following Diagnostic & Statistical Manual of Mental Disorders (DSM-IV) criteria, and the total score on the Montgomery-Asberg Depression Rating Scale, along three assessment points at 4, 8 and 12 weeks of treatment with interferon. There will also be a follow-up period of up to 6 months after treatment with interferon is completed.

Study Type

Interventional

Enrollment (Actual)

133

Phase

  • Phase 2

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

      • Alcorcon, Spain
        • Fundación Hospital Alcorcón
      • Avila, Spain
        • Hospital Nuestra Senora de Sonsoles
      • Badalona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
      • Barcelona, Spain
        • Hospital del Mar
      • Madrid, Spain
        • Hospital Ramon y Cajal
      • Madrid, Spain
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Hospital Puerta de Hierro
      • Madrid, Spain
        • Hospital Universitario La Princesa
      • Sabadell, Spain
        • Hospital Parc Tauli
      • Salamanca, Spain
        • Hospital Universitario de Salamanca
      • Tarrasa, Spain
        • Hospital Consorci Sanitari De Terrassa
      • Valencia, Spain
        • Hospital la Fe
      • Valencia, Spain
        • Hospital General Universitario
      • Valencia, Spain
        • Hospital Clínico Universitario
      • Zaragoza, Spain
        • Hospital Miguel Servet

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 to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with chronic hepatitis C who are going to initiate treatment with peginterferon alfa2a + ribavirin.
  • Age 18-65 years.
  • Signed informed consent.
  • If female, they are not in fertile period or they use barrier contraceptives.
  • Patients able to understand and fill written questionnaires.

Exclusion Criteria:

  • Hepatic cirrhosis or carcinoma.
  • Less than 4000/mm3 leucocytes, or less than 70000/mm3 platelets.
  • Hemoglobin less than 11 g/dL (females) or 12 (males).
  • Any risk factor for hemolysis.
  • Comorbid severe medical conditions (kidney, immune system, lung, heart, thyroid, etc).
  • Baseline mental disorders that require antidepressants (depressive disorders and anxiety disorders).
  • Other baseline mental disorders (delirium, substance use disorders).
  • Mental disorders at any time (dementia, psychotic disorders, bipolar disorders.
  • Contraindications of escitalopram (hypersensibility, diabetes, patients using serotoninergic agents, drugs that enhance the risk of bleeding, or monoamineoxidase inhibitors -MAOIs-).

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 pill
Placebo
Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy.
Experimental: Escitalopram
Escitalopram, 15 mg/day
15 mg/day starting 2 weeks before and 12 weeks during interferon therapy
Other Names:
  • Cipralex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Developed a Major Depressive Episode According to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Criteria During the First 12 Weeks of Antiviral Treatment.
Time Frame: First three months of interferon treatment.

At least five of the symptoms have been present during the same 1-week period: depressed mood, loss of interest or pleasure, weight or appetite changes, insomnia, agitation or retardation, fatigue, feelings of worthlessness or guilt, diminished ability to think or concentrate, recurrent thoughts of death.

At least one of the symptoms is either depressed mood or loss of interest. Diagnoses were made by a trained psychiatrist who applied the mood disorders module from the Structured Clinical Interview for DSM-IV Axis I Disorders, non-patient edition (SCID-I/NP) at each study evaluation.

First three months of interferon treatment.
Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid).
Time Frame: Six months after the end of interferon treatment

Number of participants with negativization of serum hepatitis C Virus Ribonucleic Acid (HCV RNA) 6 months after concluding antiviral therapy (sustained viral response).

Negativization was defined as the absence of detectable levels of serum HCV RNA using a polymerase chain reaction.

Six months after the end of interferon treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Score in the Montgomery-Asberg Depression Rating Scale
Time Frame: 12 weeks after interferon treatment onset

The MADRS is a 10-item scale, clinician-administered, which is sensitive to symptom change during antidepressant treatment. It has been frequently used to measure depressive symptoms during interferon-alpha therapy and exhibits improved internal consistency in patients with co-morbid medical conditions compared with other clinician-administered questionnaires.

Items are rated on a scale of 0-6. Scores range from 0 to 60, higher scores meaning higher levels of depression.

12 weeks after interferon treatment onset
Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale.
Time Frame: 12 weeks after interferon treatment onset

The Hospital Anxiety and Depression Scale (HADS) is 14-item scale, patient-administered, that allows two independent scores of depression and anxiety. It has been specially designed to apply in patients with comorbid medical conditions as it excludes somatic or vegetative symptoms from the depression subscale.

We present data of de depression subscale. The seven-item Depression subscale yields a score of 0-21, with higher scores meaning higher levels of depressive symptoms.

12 weeks after interferon treatment onset

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Crisanto Diez-Quevedo, MD, Germans Trias i Pujol University Hospital
  • Principal Investigator: Ramon Planas, MD, Germans Trias i Pujol University Hospital

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.

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

March 1, 2005

Primary Completion (Actual)

October 1, 2007

Study Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 14, 2005

Study Record Updates

Last Update Posted (Actual)

August 17, 2020

Last Update Submitted That Met QC Criteria

August 5, 2020

Last Verified

August 1, 2020

More Information

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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