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

NCT02469012 | Unknown

• 1 other identifier: 228/14
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatitis C, Chronic

Keywords

chronic hepatitis C; antiviral treatment; interferon-free; neurocognitive performance; emotional state; quality of life

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Change in Fatigue (Fatigue Impact Scale - FIS-D, questionnaire)

  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

• Change in Health-Related Quality of Life (SF-36, questionnaire)

  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

• Change in Emotional State (Hospital Anxiety and Depression Scale HADS, questionnaire)

  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

Study Arms (1)

IFN-free antiviral treatment

EXPERIMENTAL

Combination #1 or Combination #2 or Combination #3 or Combination #4 or Combination #5

Drug: Combination #1; Drug: Combination #2; Drug: Combination #3; Drug: Combination #4; Drug: Combination #5

Interventions

Combination #1 DRUG

Sofosbuvir + Ribavirin

Also known as: Sofosbuvir + Ribavirin

IFN-free antiviral treatment

Combination #2 DRUG

Sofosbuvir + Daclatasvir

Also known as: Sofosbuvir + Daclatasvir

IFN-free antiviral treatment

Combination #3 DRUG

Sofosbuvir + Daclatasvir + Ribavirin

Also known as: Sofosbuvir + Daclatasvir + Ribavirin

IFN-free antiviral treatment

Combination #4 DRUG

Sofosbuvir + Ledipasvir

Also known as: Sofosbuvir + Ledipasvir

IFN-free antiviral treatment

Combination #5 DRUG

Sofosbuvir + Ledipasvir + Ribavirin

Also known as: Sofosbuvir + Ledipasvir + Ribavirin

IFN-free antiviral treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wuerzburg: lead

Study Sites (1)

Kreiskliniken Altötting-Burghausen, Medizinische Klinik II

Burghausen, Bavaria, 84489, Germany

RECRUITING

Related Publications (14)

• 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.

  PMID: 19897823 RESULT

• 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. doi: 10.3758/bf03193146.

  PMID: 17695343 RESULT

• 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, Nelson DR; POSITRON Study; FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 May 16;368(20):1867-77. doi: 10.1056/NEJMoa1214854. Epub 2013 Apr 23.

  PMID: 23607593 RESULT

• 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.

  PMID: 15637534 RESULT

• Kraus MR, Schafer A, Teuber G, Porst H, Sprinzl K, Wollschlager 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. Epub 2013 Jun 24.

  PMID: 23300053 RESULT

• 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 AM, Younossi Z, Gane EJ. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 May 16;368(20):1878-87. doi: 10.1056/NEJMoa1214853. Epub 2013 Apr 23.

  PMID: 23607594 RESULT

• Schafer 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. German.

  PMID: 23059806 RESULT

• 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 W, Pasquinelli C, Grasela DM; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218.

  PMID: 24428467 RESULT

• Alter MJ. The epidemiology of acute and chronic hepatitis C. Clin Liver Dis. 1997 Nov;1(3):559-68, vi-vii. doi: 10.1016/s1089-3261(05)70321-4.

  PMID: 15560058 RESULT

• 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: Edizioni Minerva Medica, 1997

  RESULT

• 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.

  PMID: 12823087 RESULT

• 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. doi: 10.1016/s0165-0327(02)00264-1.

  PMID: 12450640 RESULT

• 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(Suppl 1):I1-21. doi: 10.1136/gut.49.suppl_1.i1. No abstract available.

  PMID: 11413125 RESULT

• 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. doi: 10.1176/appi.psy.44.2.104.

  PMID: 12618532 RESULT

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Sofosbuvir; Ribavirin; daclatasvir; ledipasvir, sofosbuvir drug combination; 5-fluorouracil, salicylic acid drug combination; ledipasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Michael R Kraus, MD, PhD

  Kreiskliniken Altötting-Burghausen, Burghausen, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arne Schäfer, PhD

CONTACT

+49931201402; arne.schaefer@me.com

Michael R Kraus, MD, PhD

CONTACT

+4986778801; m.kraus@krk-bgh.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. Arne Schaefer

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: June 11, 2015
• Study Start: October 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: April 1, 2017
• Last Updated: June 11, 2015

Record last verified: 2015-06

Locations

DE (1)