Effects of Direct-acting Antiviral Agents on HCV Cognitive Function, and Depression in HCV Related Cirrhosis: A Prospective Clinical Trial

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ClinicalTrials.gov Identifier: NCT04330508

Recruitment Status : Recruiting

First Posted : April 1, 2020

Last Update Posted : September 28, 2021

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Sponsor:

Information provided by (Responsible Party):

Madhumita Premkumar, Postgraduate Institute of Medical Education and Research

Study Description

Brief Summary:

Minimal hepatic encephalopathy (MHE) is an important clinical variant of hepatic encephalopathy (HE), which occurs in up to 60-70% of patients with cirrhosis. The condition comprises a cognitive impairment, observed in patients with cirrhosis who have no clinical evidence of overt hepatic encephalopathy (OHE). It is associated with an increased incidence of road traffic accidents, reduced quality of life and it affects the ability to perform tasks of daily living. Successful treatment of hepatitis C has been reported to be associated with 62-84% reduction in all-cause mortality (deaths), 68-79% reduction in risk of HCC and 90% reduction in risk of liver transplantation. In addition, studies have shown that viral eradication may improve cognition when given interferon based regimens for HCV. With the available of safe, efficacious, all oral regimens for HCV, we plan to prospectively analyse the change in mood, depression and cognitive function in response to DAA therapy, in relation to outcomes of treatment.

Condition or disease	Intervention/treatment
Depression in Chronic Hepatitis C	Other: Depression and Cognitive Tests

Detailed Description:

Investigations will be performed according to the Declaration of Helsinki and approval of the enrolment as well as the usage of patient blood samples for research purpose will be obtained from the institutional ethics committee, and written informed consent will be obtained from all patients.The primary analysis upon which the sample size consideration was based involved the comparison of the SVR subgroup and the subgroup of patients without SVR. For the sample size calculation, we a two-factorial design (time course × SVR) with the use of a two-way analysis of variance (ANOVA) analysis, a significance level of 5% and a statistical power of at least 80% to detect a medium effect size (d = 0.5) and thus to show a significant group difference. Based on this background, the optimal sample size is calculated to be a total of 102 subjects. To consider asymmetric subgroups and to allow for a moderate dropout rate and additional calculations (secondary study objectives), we aim to include a total of at least 150 study participants in each group with 25 healthy volunteers as controls.

Study Design

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Study Type :	Observational
Estimated Enrollment :	350 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Effects of Direct-acting Antiviral Agents on Cognitive Function, and Depression in Chronic Hepatitis C
Actual Study Start Date :	March 1, 2018
Estimated Primary Completion Date :	October 31, 2021
Estimated Study Completion Date :	December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Depression North American Indian childhood cirrhosis

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Genetic and Rare Diseases Information Center resources: Hepatic Encephalopathy Chronic Graft Versus Host Disease

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Group A Chronic hepatitis C without Cirrhosis	Other: Depression and Cognitive Tests Health Related Quality of Life, neurocognitive tests, PHES Other Name: SF36
Chronic hepatitis C with Cirrhosis	Other: Depression and Cognitive Tests Health Related Quality of Life, neurocognitive tests, PHES Other Name: SF36
Healthy Volunteers

Outcome Measures

Primary Outcome Measures :

Cognitive performance [ Time Frame: Day 0 ]
Computerized battery (Reaction times, simple and choice, visual memory, Number connection test, and Inhibitory Control Test)
Cognitive performance [ Time Frame: 90 days after treatment completion ]
Computerized battery (Reaction times, simple and choice, visual memory, Number connection test, and Inhibitory Control Test)
Cognitive performance using conventional tests [ Time Frame: Day 0 ]
Psychometric hepatic encephalopathy score (PHES), Indian Version.
Cognitive performance using conventional tests [ Time Frame: 90 days after treatment completion ]
Psychometric hepatic encephalopathy score (PHES), Indian Version.
HRQOL by SF-36 [ Time Frame: Day 0 ]
HRQOL by SF-36 [ Time Frame: 90 days after treatment completion ]

Secondary Outcome Measures :

Depression Scale [ Time Frame: Day 0 ]
Beck's Depression Inventory (BDI) Generalized anxiety disorder (GAD 7 score) Psychometric hepatic encephalopathy Score (PHES) Montreal Cognitive assessment Score (MoCA Score)
Depression Scale [ Time Frame: 90 days after treatment completion ]
Beck's Depression Inventory (BDI) Generalized anxiety disorder (GAD 7 score) Psychometric hepatic encephalopathy Score (PHES) Montreal Cognitive assessment Score (MoCA Score)

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Patients with Chronic hepatitis C Infection

Criteria

Inclusion Criteria:

Age 18-65 years and chronic HCV infection.
Group A: Patients with hepatitis C (Non-cirrhotic) [n= 150]
Group B: Patients with hepatitis C related compensated-cirrhosis [n= 150]
Group C: Healthy volunteers [n= 25]

Exclusion Criteria:

Current overt hepatic encephalopathy or during the last 1 month
TIPS (transjugular intra- hepatic porto-systemic shunt)
elective surgery planned within the next 8 weeks
unable to give informed consent
HIV infection
chronic respiratory insufficiency
current infection and receiving antibiotics
renal failure (serum creatinine ≥ 1.5 mg/l)
hepatocellular carcinoma,
patient with other neurological disease
intake of sedatives, antidepressants, benzodiazepines, or benzodiazepines-antagonists (flumazenil, neuromuscular blocking agents)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04330508

Contacts

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Contact: Madhumita Premkumar, DM	01722756344	drmadhumitap@gmail.com

Locations

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India
Postgraduate Institute of Medical Education and Research	Recruiting
Chandigarh, India, 160012
Contact: Madhumita PREMKUMAR

Sponsors and Collaborators

Postgraduate Institute of Medical Education and Research

Investigators

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Principal Investigator:	Madhumita Premkumar, DM	Postgraduate Institute of Medical Education and Research

More Information

Publications:

Butterworth RF. Editorial: rifaximin and minimal hepatic encephalopathy. Am J Gastroenterol. 2011 Feb;106(2):317-8. doi: 10.1038/ajg.2010.460.

Poordad FF. Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther. 2007 Feb;25 Suppl 1:3-9. doi: 10.1111/j.1746-6342.2006.03215.x.

Amodio P, Montagnese S, Gatta A, Morgan MY. Characteristics of minimal hepatic encephalopathy. Metab Brain Dis. 2004 Dec;19(3-4):253-67. doi: 10.1023/b:mebr.0000043975.01841.de.

Kircheis G, Knoche A, Hilger N, Manhart F, Schnitzler A, Schulze H, Haussinger D. Hepatic encephalopathy and fitness to drive. Gastroenterology. 2009 Nov;137(5):1706-15.e1-9. doi: 10.1053/j.gastro.2009.08.003. Epub 2009 Aug 15.

Ortiz M, Cordoba J, Jacas C, Flavia M, Esteban R, Guardia J. Neuropsychological abnormalities in cirrhosis include learning impairment. J Hepatol. 2006 Jan;44(1):104-10. doi: 10.1016/j.jhep.2005.06.013. Epub 2005 Jul 11.

Bajaj JS, Schubert CM, Heuman DM, Wade JB, Gibson DP, Topaz A, Saeian K, Hafeezullah M, Bell DE, Sterling RK, Stravitz RT, Luketic V, White MB, Sanyal AJ. Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology. 2010 Jun;138(7):2332-40. doi: 10.1053/j.gastro.2010.02.015. Epub 2010 Feb 20.

Bajaj JS, Saeian K, Schubert CM, Hafeezullah M, Franco J, Varma RR, Gibson DP, Hoffmann RG, Stravitz RT, Heuman DM, Sterling RK, Shiffman M, Topaz A, Boyett S, Bell D, Sanyal AJ. Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test. Hepatology. 2009 Oct;50(4):1175-83. doi: 10.1002/hep.23128.

Conn HO. Trailmaking and number-connection tests in the assessment of mental state in portal systemic encephalopathy. Am J Dig Dis. 1977 Jun;22(6):541-50. doi: 10.1007/BF01072510. No abstract available.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kaur H, Dhiman RK, Kulkarni AV, Premkumar M, Singh V, Duseja AK, Grover S, Grover GS, Roy A, Verma N, De A, Taneja S, Mehtani R, Mishra S, Kaur H. Improvement of chronic HCV infection-related depression, anxiety, and neurocognitive performance in persons achieving SVR-12: A real-world cohort study. J Viral Hepat. 2022 May;29(5):395-406. doi: 10.1111/jvh.13668. Epub 2022 Mar 17.

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Responsible Party:	Madhumita Premkumar, Assistant professor, Department of heaptology, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:	NCT04330508
Other Study ID Numbers:	IEC-D3/2018-866
First Posted:	April 1, 2020 Key Record Dates
Last Update Posted:	September 28, 2021
Last Verified:	September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Madhumita Premkumar, Postgraduate Institute of Medical Education and Research:


Neurocognition, Minimal hepatic encephalopathy, Direct antivirals, DAAs, Chronic hepatitis C

Additional relevant MeSH terms:

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Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic Depression Depressive Disorder Behavioral Symptoms Mood Disorders Mental Disorders Liver Diseases	Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Infections Enterovirus Infections Picornaviridae Infections RNA Virus Infections Blood-Borne Infections Communicable Diseases Flaviviridae Infections

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