Long-Term Evaluation Follow-up of Neurocognitive Performance and Emotional State in Patients With Chronic Hepatitis C

NCT ID: NCT00227149

Last Updated: 2009-02-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 197 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2008-08-31

Brief Summary

This is a long-term evaluation follow-up study of neurocognitive performance and emotional state in patients with chronic hepatitis C infection and a former (peg)interferon alfa-2b-based therapy.

M.R. Kraus, G. Teuber, NN, NN (MPsych), M. Scheurlen

Questions:

• Neurocognitive and psychiatric changes induced by interferon alfa-2b therapy in patients with chronic hepatitis C - are they fully reversible in long-term follow-up after the end of antiviral treatment?
• At least 12 months after the end of antiviral treatment - are neurocognitive and mood-related parameters even significantly improved as compared to pretreatment values? Is this possibly only true of patients with successful virus eradication?
• At least 12 months after the end of antiviral treatment, is there a significant difference between patients with and without sustained virological response with respect to neurocognitive performance, emotional state and quality of life?
• In the absence of clinically significant liver damage in patients with chronic hepatitis C - does the mere presence of the hepatitis C virus have any significant influence on neurocognitive or attentional performance?
• Does the study data support an additional indication for antiviral therapy in chronic hepatitis C? In the case of successful virus eradication, emotional state and - above all - is neurocognitive performance significantly improved even in the absence of severe liver damage?

Detailed Description

This is a long-term evaluation follow-up study of neurocognitive performance and emotional state in patients with chronic hepatitis C infection and a former (peg)interferon alfa-2b-based therapy.

M.R. Kraus, G. Teuber, NN, NN (MPsych), M. Scheurlen

Questions:

• Neurocognitive and psychiatric changes induced by interferon alfa-2b therapy in patients with chronic hepatitis C - are they fully reversible in long-term follow-up after the end of antiviral treatment?
• At least 12 months after the end of antiviral treatment - are neurocognitive and mood-related parameters even significantly improved as compared to pretreatment values? Is this possibly only true of patients with successful virus eradication?
• At least 12 months after the end of antiviral treatment, is there a significant difference between patients with and without sustained virological response with respect to neurocognitive performance, emotional state and quality of life?
• Can the results of the current and previous studies be confirmed by alternative / additional psychometric instruments in specified subsample? (Fatigue Impact Scale; FIS-D, SF-36)
• In the absence of clinically significant liver damage in patients with chronic hepatitis C - does the mere presence of the hepatitis C virus have any significant influence on neurocognitive or attentional performance?
• Does the study data support an additional indication for antiviral therapy in chronic hepatitis C? In the case of successful virus eradication, is emotional state and - above all - neurocognitive performance significantly improved even in the absence of severe liver damage?

Methods:

• Multifactorial analysis of test results: pre- vs. post-therapy; sustained virological response vs. nonresponse/relapse.
• Psychometric evaluation instruments / psychometric questionnaires (HADS-D, SCL-90-R, Subsample : SF-36, FIS-D)
• Evaluation of neurocognitive performance by the Test battery of Attentional Performance (TAP)
• Evaluation in a prospective, longitudinal study design.

Planned sample size / sample size considerations

• N = 150 patients (hepatitis C patients in a longitudinal study design: t1[before onset of interferon therapy] … t5[at least 12 months after the end of antiviral treatment]

Power calculations / power considerations:

• Given: 2-factorial design (time course x SVR); type I error = 0.050; type II error = 0.20 (power = 0.80) - as usually assumed in clinical trials.
• With respect to the independent factor SVR ("sustained virological response", 2 factor levels), optimum / optimal sample sizes range from 42 (large effect size d = 0.8) to 102 (medium effect size d = 0.5). Smaller effect sizes - according to previous work in this field - do not appear to bear any clinical relevance.
• (Pairwise comparisons of dependent samples [e.g. pre- vs. post-therapy or pre-therapy vs. long-term follow-up] require even smaller optimal sample sizes ranging from 16 to 43 for large or medium effect sizes.)

Patient recruitment:

• Patients with chronic hepatitis C infection and therapy with (peg)interferon alfa-2b.
• Patients with informed written consent (with respect) to a long-term follow-up of psychiatric side effects and neurocognitive performance.
• Patients with baseline monitoring of neuropsychiatric symptoms and neurocognitive performance.

Conditions

Hepatitis C, Chronic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Patients with chronic hepatitis C and indication for interferon-based antiviral therapy.
• Written informed consent to study participation, especially to long-term follow-up monitoring of psychiatric and neurocognitive side effects of combination therapy with (peg)interferon alfa-2b and ribavirin.
• Age of study participants: between 18 and 65 years.
• All patients need to have documented antibodies to hepatitis C virus (HCV) and circulating HCV-RNA as measured by reverse-transcription polymerase chain reaction (Cobas Amplicor HCV Monitor™ test, Roche Diagnostics)

Exclusion Criteria

• Insufficient knowledge of the German language or cognitive impairment (due to the indispensable application of questionnaires and the TAP, test battery of attentional performance).

• Age under 18 years or over 65 years
• Coinfections such as hepatitis B virus or human immunodeficiency virus
• Severe internal diseases (e.g., cancer, ischemic heart disease, autoimmune disease)
• Major depressive disorder (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria), psychosis, active intravenous drug use or alcohol abuse.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schering-Plough

INDUSTRY

Sponsor Role: collaborator

University of Wuerzburg

OTHER

Sponsor Role: lead

Responsible Party

University of Wuerzburg

Principal Investigators

Michael R. Kraus, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Med. Klinik und Poliklinik II, University of Wuerzburg

Locations

Med. Klinik und Poliklinik II, University of Wuerzburg

Würzburg, , Germany

Countries

Germany

References

Kraus MR, Schafer A, Wissmann S, Reimer P, Scheurlen M. Neurocognitive changes in patients with hepatitis C receiving interferon alfa-2b and ribavirin. Clin Pharmacol Ther. 2005 Jan;77(1):90-100. doi: 10.1016/j.clpt.2004.09.007.

Reference Type: BACKGROUND

PMID: 15637534 (View on PubMed)

Kraus MR, Schafer A, Faller H, Csef H, Scheurlen M. Psychiatric symptoms in patients with chronic hepatitis C receiving interferon alfa-2b therapy. J Clin Psychiatry. 2003 Jun;64(6):708-14. doi: 10.4088/jcp.v64n0614.

Reference Type: BACKGROUND

PMID: 12823087 (View on PubMed)

Kraus MR, Schafer A, Faller H, Csef H, Scheurlen M. Paroxetine for the treatment of interferon-alpha-induced depression in chronic hepatitis C. Aliment Pharmacol Ther. 2002 Jun;16(6):1091-9. doi: 10.1046/j.1365-2036.2002.01265.x.

Reference Type: BACKGROUND

PMID: 12030950 (View on PubMed)

Kraus MR, Schafer A, Scheurlen M. Paroxetine for the prevention of depression induced by interferon alfa. N Engl J Med. 2001 Aug 2;345(5):375-6. No abstract available.

Reference Type: BACKGROUND

PMID: 11484704 (View on PubMed)

Other Identifiers

PO 4406

Identifier Type: -

Identifier Source: org_study_id