Clinical trial NCT00136318: Escitalopram for the Prevention of PEGASYS-associated Depression in Hepatitis C Virus-infected Patients
Official title: Efficacy and Tolerability of Escitalopram for the Prevention of Pegylated Interferon Alfa Associated Depression in Patients With Chronic Hepatitis C Infection: a Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depression
Keywords: Pegasys-Induced depression
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2005-08-29
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Primary end points

* incidence of depression defined as a Montgomery Asberg Depression Scale Score (MADRS) of 13 or higher during antiviral therapy (up to 48 weeks, depending on genotype)
* effect of an antidepressive pre-treatment over two weeks and a continuously concomitant treatment with Escitalopram (S-citalopram) on frequency and severity of depression in patients with chronic hepatitis C (HCV) treated with Peg-interferon alfa-2a (PEGASYS) and ribavirin, measured by the Montgomery Asberg Depression Scale

Secondary end points

* time to depression defined as a MADRS score of 13 or higher
* incidence of major depression defined by Diagnostic and Statistical Manual IV (DSM-IV) criteria
* severe depression according to MADRS scale (score 25 or higher)
* Health related quality of life (HRQOL) measured by the Short Form 36 (SF-36)
* sustained virologic response
* tolerability
* safety
* changes/group differences in other psychiatric depression scales (Hamilton Depression Rating Scale, Beck Depression Inventory)

Other investigations:

* cognitive function, anxiety (word fluency test, trail making test part A and B, othe scales)
* Predictive parameters for patients especially gaining from an antidepressive therapy (e.g. age, gender, weight, height, alanine aminotransferase (ALAT) quotient defined as median ALAT values before treatment divided by the upper standard value, HCV-RNA serum concentration level of fibrosis in liver histology, baseline values of the different psychometric scales)
* alanine aminotransferase (ALAT), aspartate transaminase (ASAT), thyrotrophin (TSH)
* biomarkers (genetic parameters, cytokines,...)


Eligibility criteria: Inclusion Criteria:

* Chronic hepatitis C infection defined as positive anti-HCV antibodies and serum HCV-RNA \>1000 IU/ml, naive to antiviral treatment
* age \>18 years

Exclusion Criteria:

* Antidepressive treatment within the last 3 years
* Psychiatric diseases including major depressive disorders in past medical history
* Active substance abuse during the last 12 months
* Pregnancy, lactation, wish to become pregnant
* Hepatitis B (HBV)/HIV-coinfection
* Decompensated liver disease, hepatocellular carcinoma, history of bleeding esophageal varices
* Neutropenia (\<1500/ul), thrombocytopenia (\<70/nl), anemia (\<12g/dl in females, \<13g/dl in males)
* History of autoimmune disease
* History of organ transplantation, concomitant liver disease, severe cardiopulmonary disease, hemolytic anemia, malignant disease

Primary outcomes:
measure: Montgomery Asberg Depression Scale (MADRS) With a Score of 13 or Higher
timeFrame: 50 weeks for genotypes 1 or 4 and 26 weeks for patients with genotype 2 or 3
Secondary outcomes:
measure: Proportion of Patients Without Depression (Defined as a MADRS Score of 13 or Higher)
timeFrame: Patients free of depression during 24 or 48 weeks of antiviral therapy
measure: Incidence of Major Depression Defined by Diagnostic and Statistical Manual IV (DSM-IV) Criteria
timeFrame: major depression during 24 or 48 weeks of antiviral therapy
measure: Severe Depression Defined as a MADRS Score of 25 or Higher
timeFrame: severe depression during 24 or 48 weeks of antiviral therapy
measure: Health Related Quality of Life (HRQOL) Measured by the Short Form 36 (SF-36)
timeFrame: assessed 2,4,12,24 and 48 weeks of antiviral treatment
measure: Sustained Virologic Response
timeFrame: assessed 24 weeks after end of antiviral treatment
measure: Tolerability
timeFrame: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment
measure: Safety
timeFrame: assessed 2,4,12,24 and for genotype 1 and 4, 48 weeks of antiviral treatment
Other outcomes:
Locations:
city: Leipzig
country: Germany
facility: Department of Gastroenterolgy and Rheumatology, Sektion Hepatology
Study officials:
affiliation: Charité
name: Thomas Berg, Prof. Dr.
role: STUDY_CHAIR
affiliation: Charite University, Berlin, Germany
name: Martin Schaefer, Prof. Dr.
role: STUDY_CHAIR
References:
citation: Sarkar S, Sarkar R, Berg T, Schaefer M. Sadness and mild cognitive impairment as predictors for interferon-alpha-induced depression in patients with hepatitis C. Br J Psychiatry. 2015 Jan;206(1):45-51. doi: 10.1192/bjp.bp.113.141770. Epub 2014 Oct 30.
citation: Schaefer M, Sarkar R, Knop V, Effenberger S, Friebe A, Heinze L, Spengler U, Schlaepfer T, Reimer J, Buggisch P, Ockenga J, Link R, Rentrop M, Weidenbach H, Fromm G, Lieb K, Baumert TF, Heinz A, Discher T, Neumann K, Zeuzem S, Berg T. Escitalopram for the prevention of peginterferon-alpha2a-associated depression in hepatitis C virus-infected patients without previous psychiatric disease: a randomized trial. Ann Intern Med. 2012 Jul 17;157(2):94-103. doi: 10.7326/0003-4819-157-2-201207170-00006.