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

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
H. Lundbeck A/S
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00166296
First received: September 9, 2005
Last updated: March 4, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder.
Hepatitis C, Chronic
Drug: Escitalopram
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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.


  • 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 ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Total Score in the Montgomery-Asberg Depression Rating Scale [ Time Frame: 12 weeks after interferon treatment onset ] [ Designated as safety issue: No ]

    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.


  • Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale. [ Time Frame: 12 weeks after interferon treatment onset ] [ Designated as safety issue: No ]

    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.



Enrollment: 133
Study Start Date: March 2005
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escitalopram
Escitalopram, 15 mg/day
Drug: Escitalopram
15 mg/day starting 2 weeks before and 12 weeks during interferon therapy
Other Name: Cipralex
Placebo Comparator: Placebo pill
Placebo
Drug: Placebo
Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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-).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00166296

Locations
Spain
Fundacion Hospital Alcorcon
Alcorcon, Spain
Hospital Nuestra Señora de Sonsoles
Avila, Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Spain, 08916
Hospital del Mar
Barcelona, Spain
Hospital Universitario La Princesa
Madrid, Spain
Hospital Ramon y Cajal
Madrid, Spain
Hospital Puerta de Hierro
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Parc Tauli
Sabadell, Spain
Hospital Universitario de Salamanca
Salamanca, Spain
Hospital Consorci Sanitari de Terrassa
Tarrasa, Spain
Hospital Clínico Universitario
Valencia, Spain
Hospital General Universitario
Valencia, Spain
Hospital La Fe
Valencia, Spain
Hospital Miguel Servet
Zaragoza, Spain
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Hoffmann-La Roche
H. Lundbeck A/S
Investigators
Principal Investigator: Crisanto Diez-Quevedo, MD Germans Trias i Pujol University Hospital
Principal Investigator: Ramon Planas, MD Germans Trias i Pujol University Hospital
  More Information

Publications:
Responsible Party: Crisanto Diez-Quevedo, Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier: NCT00166296     History of Changes
Other Study ID Numbers: PSQHEPGTP1, EudraCT number: 2004-002982-19
Study First Received: September 9, 2005
Results First Received: February 8, 2011
Last Updated: March 4, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Germans Trias i Pujol Hospital:
Major depressive disorder, chemically induced.
Peginterferon alfa-2a.
Escitalopram.
Chronic hepatitis C, psychology.
Prophylactic treatment.

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Behavioral Symptoms
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
Mental Disorders
Mood Disorders
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Citalopram
Dexetimide
Interferons
Anti-Dyskinesia Agents
Anti-Infective Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antineoplastic Agents
Antiparkinson Agents
Antiviral Agents
Autonomic Agents

ClinicalTrials.gov processed this record on November 27, 2014