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

Completed

• Conditions: Depression in Chronic Hepatitis C
• Interventions: Other: Depression and Cognitive Tests

• Registration Number: NCT04330508
• Lead Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

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.

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 Timeline

• Study Start: 2018-03-01
• Study First Submitted: 2020-03-23
• Study First Submitted QC: 2020-03-30
• Study First Posted: 2020-04-01
• Primary Completion: 2021-10-31
• Study Completion: 2021-12-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-12
• Last Update Posted: 2024-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 385

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Chronic hepatitis C with Cirrhosis	Depression and Cognitive Tests	-
Group A	Depression and Cognitive Tests	Chronic hepatitis C without Cirrhosis

Primary Outcome Measures

Name	Time	Method
Cognitive performance	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	90 days after treatment completion	Psychometric hepatic encephalopathy score (PHES), Indian Version.
HRQOL by SF-36	90 days after treatment completion

Secondary Outcome Measures

Name	Time	Method
Depression Scale	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)

Trial Locations

Locations (1)

Postgraduate Institute of Medical Education and Research; 🇮🇳 Chandigarh, India