Neurocognitive Performance and Emotional State in HCV Patients With IFN-free Antiviral Therapy

Hepatitis C, Chronic Clinical Trial

— IFNfreeCOG  

Official title:

Evaluation of Quality of Life, Neurocognitive Performance, Fatigue, and Emotional State in HCV Patients Before, During, and in the (Long-term) Follow-up of an IFN-free Antiviral Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02469012
• Other study ID #: 228/14
• Status: Recruiting
• Phase: N/A
• First received: May 5, 2015
• Last updated: June 8, 2015
• Start date: October 2014
• Est. completion date: April 2017

Study information

• Verified date: June 2015
• Source: University of Wuerzburg
• Contact: Arne Schäfer, PhD
• Phone: +49931201402
• Email: arne.schaefer[@]me.com
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The present study evaluates neurocognitive performance as well as measures of mood, quality of life, and fatigue in patients with chronic hepatitis C infection. In a prospective longitudinal study design, included patients are monitored before, during, and in the long-term follow-up of interferon-free antiviral treatment (Sofosbuvir +/-Daclatasvir +/- Ribavirin or Sofosbuvir/Ledipasvir +/- Ribavirin). Main study goals are to compare post therapy results of sustained virologic responders to corresponding pretreatment values as well as to historic interferon-treatment patients without virological response. It is expected that HCV-associated neuropsychiatric symptoms and neurocognitive impairment is - at least in part - reversible by the successful application of modern IFN-free antiviral medication.

Description:

Chronic hepatitis C is one of the most frequent infectious diseases worldwide and a major cause of chronic liver disease. At diagnosis, approximately 20 % of patients with chronic hepatitis C already have liver cirrhosis.

Therapy for hepatitis C has meanwhile reached a high level of efficacy and effectiveness: at present, about 90 % of patients treated with a combination of peginterferon alfa, ribavirin and sofosbuvir for up to 12 weeks will reach a sustained loss of hepatitis C virus.

Psychiatric side effects of interferon alfa are well known and may require dose reduction or even premature discontinuation of therapy.

As patients on interferon treatment sometimes report concentration or memory impairment that in some cases interferes considerably with their capacity to manage the requirements of everyday life, the investigators planned and intend to conduct a prospective and longitudinal study evaluating - among other parameters - neurocognitive performance before, during, and after therapy with an antiviral IFN-free therapy.

In previously performed scientific work, the investigators were able to show that interferon-based combination therapy of chronic hepatitis C may cause reversible impairment of neurocognitive performance during treatment period. Moreover, the investigators have recently demonstrated that successful IFN-based antiviral treatment (criterion: SVR, sustained virological response) leads to significant improvement of relevant aspects of attentional and neurocognitive performance. These results indicate that HCV-related neurocognitive impairment is potentially reversible.

Nevertheless, there are still open questions and important issues to be addressed in connection with this field of research, especially regarding several aspects IFN-free antiviral therapy:

Questions to be answered:

• At least 12 months after the end of successfully performed IFN-free antiviral treatment
• are psychometrically assessed parameters related to patients' quality of life, fatigue, neurocognitive performance, and mood significantly improved as compared to pretreatment (i.e., baseline) values?

• At least12 months after the end of antiviral treatment, is there a significant difference between patients with and without sustained virological response (special to historical group of IFN-treated patients without a sustained virological response) with respect to neurocognitive performance, emotional state, fatigue and quality of life?

• In the absence of a 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? Is it possible to confirm the respective findings yielded in the context of former interferon-based treatment regimens?

• With the current and upcoming IFN-free treatment options - are there still any significant therapy-related changes in symptom areas such as neurocognitive performance, mood or fatigue?

Study Design:

Prospective monocentric study with a longitudinal repeated measures design including hepatitis C patients with indication for standard IFN-free antiviral therapy (sofosbuvir/daclatasvir +/- ribavirin; sofosbuvir/ledipasvir +/- ribavirin) and a long-term follow-up of quality of life, neurocognitive performance, fatigue, and emotional state. Planned sample size: n = 30 hepatitis C patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with chronic hepatitis C and indication for interferon-free antiviral therapy.

• Written informed consent to study participation, especially to long-term follow-up monitoring of quality of life, emotional state, fatigue, and neurocognitive performance after antiviral treatment.

• Age of study participants: between 18 and 75 years.

• At study entry, all participating patients need to have documented antibodies to HCV and circulating HCV-RNA as measured by reverse-transcription polymerase chain reaction (Cobas Amplicor HCV MonitorTM 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 75 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 DSM-IV criteria), psychosis, active intravenous drug use or alcohol abuse.

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Screening

Related Conditions & MeSH terms

• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Combination #1
Sofosbuvir + Ribavirin
• Combination #2
Sofosbuvir + Daclatasvir
• Combination #3
Sofosbuvir + Daclatasvir + Ribavirin
• Combination #4
Sofosbuvir + Ledipasvir
• Combination #5
Sofosbuvir + Ledipasvir + Ribavirin

Locations

Country	Name	City	State
Germany	Kreiskliniken Altötting-Burghausen, Medizinische Klinik II	Burghausen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
University of Wuerzburg

Country where clinical trial is conducted

Germany, 

References & Publications (14)

Alter MJ. The epidemiology of acute and chronic hepatitis C. Clin Liver Dis. 1997 Nov;1(3):559-68, vi-vii. Review. — View Citation

Bonaccorso S, Marino V, Biondi M, Grimaldi F, Ippoliti F, Maes M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord. 2002 Dec;72(3):237-41. — View Citation

Booth JC, O'Grady J, Neuberger J; Thr Royal College of Physicians of London and the British Society of Gastroenterology. Clinical guidelines on the management of hepatitis C. Gut. 2001 Jul;49 Suppl 1:I1-21. — View Citation

Dieperink E, Ho SB, Thuras P, Willenbring ML. A prospective study of neuropsychiatric symptoms associated with interferon-alpha-2b and ribavirin therapy for patients with chronic hepatitis C. Psychosomatics. 2003 Mar-Apr;44(2):104-12. — View Citation

Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009 Nov;41(4):1149-60. doi: 10.3758/BRM.41.4.1149. — View Citation

Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. — View Citation

Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, Shiffman ML, Lawitz E, Everson G, Bennett M, Schiff E, Al-Assi MT, Subramanian GM, An D, Lin M, McNally J, Brainard D, Symonds WT, McHutchison JG, Patel K, Feld J, Pianko S, — View Citation

Kraus MR, Schäfer 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. — View Citation

Kraus MR, Schäfer A, Teuber G, Porst H, Sprinzl K, Wollschläger S, Keicher C, Scheurlen M. Improvement of neurocognitive function in responders to an antiviral therapy for chronic hepatitis C. Hepatology. 2013 Aug;58(2):497-504. doi: 10.1002/hep.26229. Ep — View Citation

Kraus MR, Schäfer 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. — View Citation

Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, Jacobson IM, Kowdley KV, Nyberg L, Subramanian GM, Hyland RH, Arterburn S, Jiang D, McNally J, Brainard D, Symonds WT, McHutchison JG, Sheikh — View Citation

McQuillan GM, Alter MJ, Moyer LA, Lambert SB, Margolis HS. A population-based serologic study of hepatitis C virus infection in the United States. In: Rizetto M, Purcell RH, Gerin JL, Verne G (Eds.) Viral Hepatitis and Liver Disease. Turin, Italy: Edizion

Schäfer A, Scheurlen M, Kraus MR. [Managing psychiatric side effects of antiviral therapy in chronic hepatitis C]. Z Gastroenterol. 2012 Oct;50(10):1108-13. doi: 10.1055/s-0031-1281682. Epub 2012 Oct 11. Review. German. — View Citation

Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Neurocognitive Performance (computerized TAP - Test Battery for Attentional Performance)	assessment of changes over treatment time (repeated measures design)	evaluation time points are at baseline, after 4 weeks and 12 weeks of antiviral IFN-free treatment, four weeks and 12 months after the end of antiviral IFN-free therapy	No
Secondary	Change in Fatigue (Fatigue Impact Scale - FIS-D, questionnaire)	assessment of changes over treatment time (repeated measures design)	evaluation time points are at baseline, after 4 weeks and 12 weeks of antiviral IFN-free treatment, four weeks and 12 months after the end of antiviral IFN-free therapy	No
Secondary	Change in Health-Related Quality of Life (SF-36, questionnaire)	assessment of changes over treatment time (repeated measures design)	evaluation time points are at baseline, after 4 weeks and 12 weeks of antiviral IFN-free treatment, four weeks and 12 months after the end of antiviral IFN-free therapy	No
Secondary	Change in Emotional State (Hospital Anxiety and Depression Scale HADS, questionnaire)	assessment of changes over treatment time (repeated measures design)	evaluation time points are at baseline, after 4 weeks and 12 weeks of antiviral IFN-free treatment, four weeks and 12 months after the end of antiviral IFN-free therapy	No