Depression in Chronic Hepatitis CNCT04330508
Effects of Direct-acting Antiviral Agents on HCV Cognitive Function, and Depression in HCV Related Cirrhosis: A Prospective Clinical Trial
An observational study of Depression in Chronic Hepatitis C, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression in Chronic Hepatitis C
- What is being tested?
- Depression and Cognitive Tests
- How many people
- 385 participants
- Where
- 1 siteIndia
- Study dates
- 1 Mar 2018to 31 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with Chronic hepatitis C Infection
Who may be able to join
- 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]
Who cannot join
- 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
Show all 11Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
India1 site
Postgraduate Institute of Medical Education and Research
Chandigarh, 160012
About this study
Official title: Effects of Direct-acting Antiviral Agents on Cognitive Function, and Depression in Chronic Hepatitis C
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.
Read the 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.
- Conditions
- Depression in Chronic Hepatitis C
- Being tested
- Depression and Cognitive Tests
- Keywords
- Neurocognition, Minimal hepatic encephalopathy, Direct antivirals, DAAs, Chronic hepatitis C
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Depression and Cognitive TestsOther
Also called SF36
Health Related Quality of Life, neurocognitive tests, PHES
| Study group | Role | What they receive |
|---|---|---|
| Group A | Chronic hepatitis C without Cirrhosis Receives: Other: Depression and Cognitive Tests | |
| Chronic hepatitis C with Cirrhosis | Not described Receives: Other: Depression and Cognitive Tests | |
| Healthy Volunteers | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive performance
Computerized battery (Reaction times, simple and choice, visual memory, Number connection test, and Inhibitory Control Test)
Measured: Day 0
Cognitive performance
Computerized battery (Reaction times, simple and choice, visual memory, Number connection test, and Inhibitory Control Test)
Measured: 90 days after treatment completion
Cognitive performance using conventional tests
Psychometric hepatic encephalopathy score (PHES), Indian Version.
Measured: Day 0
Cognitive performance using conventional tests
Psychometric hepatic encephalopathy score (PHES), Indian Version.
Measured: 90 days after treatment completion
HRQOL by SF-36
Measured: Day 0
HRQOL by SF-36
Measured: 90 days after treatment completion
Secondary outcomes (2)
Depression Scale
Beck's Depression Inventory (BDI) Generalized anxiety disorder (GAD 7 score) Psychometric hepatic encephalopathy Score (PHES) Montreal Cognitive assessment Score (MoCA Score)
Measured: Day 0
Depression Scale
Beck's Depression Inventory (BDI) Generalized anxiety disorder (GAD 7 score) Psychometric hepatic encephalopathy Score (PHES) Montreal Cognitive assessment Score (MoCA Score)
Measured: 90 days after treatment completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2020
- Study start1 Mar 2018
- Primary completion31 Oct 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Depression in Chronic Hepatitis CStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 385 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Madhumita Premkumar, DM, Principal investigator, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04330508
- Sponsor's protocol ID
- IEC-D3/2018-866
- Status last verified
- Feb 2024
- First submitted
- 23 Mar 2020
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Butterworth RF. Editorial: rifaximin and minimal hepatic encephalopathy. Am J Gastroenterol. 2011 Feb;106(2):317-8. doi: 10.1038/ajg.2010.460.
PubMed 21301455Poordad 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.
PubMed 17295846Amodio 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.
PubMed 15554421Kircheis 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.
PubMed 19686744Ortiz 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.
PubMed 16169117Bajaj 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.
PubMed 20178797Bajaj 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.
PubMed 19670416Conn 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.
PubMed 868833Kaur 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.
PubMed 35266624
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Direct-acting Antiviral Agents on Cognitive Function, and Depression in Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT04330508
- Acronym / sponsor ID
- IEC-D3/2018-866
- Conditions
- Depression in Chronic Hepatitis C
- Keywords
- Neurocognition, Minimal hepatic encephalopathy, Direct antivirals, DAAs, Chronic hepatitis C
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 385 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 31 Oct 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 1 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Other: Depression and Cognitive TestsChronic hepatitis C without Cirrhosis |
| Chronic hepatitis C with Cirrhosis | – | Other: Depression and Cognitive Tests |
| Healthy Volunteers | – | – |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with Chronic hepatitis C Infection
Key inclusion criteria (4 listed)
- 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]
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Depression and Cognitive TestsAlso: SF36Health Related Quality of Life, neurocognitive tests, PHES | Other | Chronic hepatitis C with Cirrhosis, Group A |
Primary outcome
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
2 secondary outcomes
Depression Scale
Time frame: Day 0
Depression Scale
Time frame: 90 days after treatment completion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Background: PubMed 21301455Butterworth RF. Editorial: rifaximin and minimal hepatic encephalopathy. Am J Gastroenterol. 2011 Feb;106(2):317-8. doi: 10.1038/ajg.2010.460.
- Background: PubMed 17295846Poordad 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.
- Background: PubMed 15554421Amodio 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.
- Background: PubMed 19686744Kircheis 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.
- Background: PubMed 16169117Ortiz 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.
- Background: PubMed 20178797Bajaj 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.
- Background: PubMed 19670416Bajaj 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.
- Background: PubMed 868833Conn 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.
- Derived from this study: PubMed 35266624Kaur 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.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Madhumita Premkumar, DM principal investigator
Post Graduate Institute of Medical Education and Research, Chandigarh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression in Chronic Hepatitis C, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive performance (time frame: Day 0). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04330508, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.