Clinical trial NCT04330508: Effects of Direct-acting Antiviral Agents on HCV Cognitive Function, and Depression in HCV Related Cirrhosis: A Prospective Clinical Trial
Official title: Effects of Direct-acting Antiviral Agents on Cognitive Function, and Depression in Chronic Hepatitis C
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depression in Chronic Hepatitis C
Keywords: Neurocognition, Minimal hepatic encephalopathy, Direct antivirals, DAAs, Chronic hepatitis C
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2020-04-01
Enrollment: 385
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with Chronic hepatitis C Infection

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.

Eligibility 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)

Primary outcomes:
measure: Cognitive performance
timeFrame: Day 0
measure: Cognitive performance
timeFrame: 90 days after treatment completion
measure: Cognitive performance using conventional tests
timeFrame: Day 0
measure: Cognitive performance using conventional tests
timeFrame: 90 days after treatment completion
measure: HRQOL by SF-36
timeFrame: Day 0
measure: HRQOL by SF-36
timeFrame: 90 days after treatment completion
Secondary outcomes:
measure: Depression Scale
timeFrame: Day 0
measure: Depression Scale
timeFrame: 90 days after treatment completion
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Madhumita Premkumar, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Butterworth RF. Editorial: rifaximin and minimal hepatic encephalopathy. Am J Gastroenterol. 2011 Feb;106(2):317-8. doi: 10.1038/ajg.2010.460.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.