Impact on QoL and Cognitive Functioning of New Antiviral Therapies in Subjects With Chronic Hepatitis HCV-related

January 8, 2019 updated by: Gioia Mura, Azienda Ospedaliero Universitaria di Cagliari

Chronic hepatitis HCV-related is the most common cause of chronic liver disease in Italy. Patients with chronic hepatitis C present a prevalence of depressive disorders higher than that of the general population; moreover, it has been repeatedly demonstrated the presence of cognitive deficits and poor quality of life. Chronic hepatitis C therapy was based on the combined use of pegylated alpha-interferons (PEG-INF), and ribavirin. Recently, new therapeutic protocols have been introduced, and while some antiviral drugs, including the first-generation ones, were used only in combination with PEG-IFN and ribavirin, the second and third generation antiviral drugs protocols are interferon-free. However, because of the high cost, the access to interferon-free protocols is only for patients with advanced fibrous stages, or with concomitant extra-hepatic HCV-related diseases, or for transplanted patients. Many side effects, such as flu-like symptoms, and psychiatric symptoms (depression, anxiety, irritability, insomnia) are common during antiviral therapy with IFN. However, in patients with chronic hepatitis C, a high lifetime prevalence of major depressive disorder, panic disorder, and brief recurrent depression have been observed, irrespective of IFN treatment and the use of alcohol and narcotics; such associations between mood and anxiety disorders and chronic hepatitis C may reflect a high prevalence of bipolar spectrum disorders. The presence of severe psychopathological symptoms requires the reduction of posology and causes high rates of discontinuation of antiviral therapy.

This project represents an innovative psychiatric and neuropsychological screening program for patients with chronic hepatitis C, eligible for antiviral therapy.

  1. Primary objectives:

    1. to verify the medium-term impact of new antiviral therapies on quality of life, psychological well-being and cognitive function in subjects with chronic hepatitis C;
    2. to verify the predictability of specific psychopathological components and specific determinants on compliance with new antiviral therapies.

  2. Main secondary objectives:

    1. to verify the evidence of association between various psychiatric disorders and cognitive deficits and chronic hepatitis C;
    2. to evaluate the relative weight of psychopathological and/or cognitive disorders on the efficacy of antiviral therapy and on quality of life.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background HCV-related chronic hepatitis represents the most common cause of chronic liver disease in Italy, with an estimated prevalence of 1-1.1% in the general population, reaching about 15% in subjects over 50 years of age. Chronic HCV infection is the cause of 27% of cases of cirrhosis and 25% of cases of hepatocarcinoma. Persons with chronic hepatitis C present a prevalence of depressive disorders higher than that of the general population (59% vs. 21%). Moreover, there has been repeatedly demonstrated the presence of cognitive deficits, mainly concerning attentive, executive, and verbal comprehension, also in the absence of liver cirrhosis and comorbidities due to the use of substances, and a reduced quality of life. Chronic hepatitis C therapy was based on the combined use of pegylated alpha interferons (PEG-INF) and ribavirin, with SVR (sustained virological response, defined as HCV-RNA undetectable in serum at six months after the end of therapy), normalization of transaminases and improvement of liver histology, altogether in 60% of cases. Recently, new antiviral drugs with direct activity (e.g. antiprotease and antipolymer activity) have been introduced into hepatitis C therapeutic protocols, with the development of PEG-INF-free therapeutic schemes. Unfortunately, because of the excessive cost, in many Countries, including Italy, the access to PEG-INF-free schemas is only for patients with advanced fibrous stages, or who have concomitant extra-hepatic viral diseases HCV-related, or those already transplanted, while others are still expected to be treated with PEG-INF and ribavirin.

There are frequent side effects of antiviral therapy, often of minor magnitude, but sometimes incompatible with the continuation of therapy or life threatening. The most common adverse effects are influenza-like symptoms, occurring in more than half of the patients, especially during the first treatment period, and psychiatric symptoms (depression, anxiety, irritability, insomnia), which occur around the third month of treatment from 12 to 41% of patients. However, in persons with chronic hepatitis C, a high lifetime prevalence of major depressive disorder and panic disorder, and brief recurrent depression have been observed, irrespective of PEG-INF treatment and the use of alcohol and narcotic drugs; such associations between mood and anxiety disorders and chronic hepatitis C may reflect a high prevalence of bipolar disorder, which is more difficult to diagnose using non-dedicated screening tools. Some symptoms before treatment start, such as lack of pleasure or interest, asthenia, loss of appetite, social withdrawal, reduced work function, and hostility, are highly predictive of the onset of depressive disorders during antiviral therapy. Poor cognitive performance prior to antiviral therapy, coupled with the only depressive symptom of sadness, is predictive of more severe depressive disorders during antiviral treatment. However, cognitive deficits found before therapy appear potentially reversible and tend to completely recede when there is a virological response sustained by antiviral therapy. The presence of severe psychopathological symptoms leads to a reduction in posology and high rates of discontinuation of antiviral therapy.

Careful psychiatric and neuropsychological evaluation before, during and after antiviral treatment should therefore be an indispensable part of screening and HCV-related chronic hepatitis therapy. This project represents an innovative psychiatric and neuropsychological screening program for persons with chronic hepatitis C, eligible for antiviral therapy. This program aims:

  • to determine which psychopathological symptoms and cognitive deficits are more frequent in persons with chronic hepatitis C;
  • to verify the impact of antiviral therapy on persons' reported quality of life, and on the onset, aggravation, maintenance of psychopathological symptoms and/or cognitive deficits;
  • to determine which psychopathological and neuropsychological symptoms are predictive to high compliance and the effectiveness of antiviral therapy;
  • to verify the existence of specific psychopathological and neuropsychological patterns in persons with chronic hepatitis C before, during and after antiviral therapy;
  • to produce a standard procedure for psychiatric and neuropsychological screening in patients with HCV-related chronic hepatitis.

Early identification of subjects at risk of psychiatric and cognitive disorders during antiviral therapy will effectively treat individuals at risk of discontinuing the antiviral therapy itself, improving the quality of the treatment and the effectiveness of the treatments.

Design Observational study on a sample of persons with chronic hepatitis C. The experimental cohort will consist of participants who will be admitted to new antiviral treatments. The control cohort will consist of subjects recruited later, for which there is no immediate possibility of access to new treatments (wait-list).

Selection of the sample

The study will be conducted at the Center for the Study of Liver Diseases at the University Hospital of Monserrato, Cagliari. It is intended for subjects with chronic hepatitis C consecutively afferent to the facility, eligible for antiviral therapy. From the whole sample of cases will be drawn two cohorts:

  1. approximately 50 subjects with chronic hepatitis C, selected to receive new antiviral therapy immediately;
  2. approximately 50 subjects with chronic hepatitis C, who are eligible to receive new antiviral therapy, but are on a waiting list for non-availability of the treatment.

Statistical analysis The data analysis will be carried out after the end of the study and in the next 3 months, by setting up a complete database for each participant, including in an anonymous form the socio-demographic and anamnestic data, and the data from the assessments performed at baseline and in subsequent times. The sample will be analyzed for frequency of lifetime and current psychiatric disorders, current cognitive deficits, subjectively perceived Quality of Life, depressive, hypomanic and manic symptoms, and patterns of biological rhythms. Data analysis will be done with multivariate techniques, for evaluating the effect and interaction of the various factors. The presence of psychiatric disorders and cognitive deficits will be considered dependent variables. The psychopathological specificity of symptoms related to antiviral treatment will also be measured in terms of different frequencies of specific psychiatric/neuropsychological symptoms and specific profiles of response to antiviral therapy. The whole sample will be compared at the baseline with a normative sample extracted with a computerized matching technique (4 controls each case) by gender and age from the database of a Italian population study. Through matchings 1: 4 it will be possible to increase the sample size and increase the statistical power of the study. The data analyses will be performed through SPSS (Statistical Package for Social Science) software.

Funding This project is a spontaneous study, without any source of funding. Ethical Aspects The study will be conducted in accordance with the ethical principles contained in the Helsinki Declaration. The final study protocol was approved by the Ethics Independent Committee of the Azienda Ospedaliero Universitaria di Cagliari (approval record N. PG/2015/16964).

Informed consent The interviewer will give clear and comprehensive information about the nature and the assumptions of the study to the respondents. Participants will also be informed of the possibility of interrupting the interview and withdrawing the consent to the study at any time. Interviewees will be required to sign an informed consent form.

Data protection The subjects enrolled in the study will be given information about data protection and the privacy law. The interviewer will explain that the study data will be placed in a database with anonymous codes to maintain confidentiality, in accordance with local data protection laws.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Cagliari
      • Monserrato, Cagliari, Italy, 09042
        • Policlinico Universitario di Monserrato

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Group 1: 50 subjects with chronic hepatitis HCV-related, which are eligible to be immediately treated with new antiviral drugs.

Group 2: 50 subjects with chronic hepatitis HCV-related, which are eligible to be treated with new antiviral drugs but are in wait list.

Description

Inclusion Criteria:

  • diagnosis of chronic hepatitis HCV-related, eligible to new antiviral drugs treatments
  • understanding Italian language
  • signed informed consent

Exclusion Criteria:

  • severe cognitive deficits

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Neuropsychiatric screening (treatment+)
Subjects affected by chronic hepatitis HCV-related, undergoing new antiviral drugs treatment, will be screened by psychiatric and neuropsychological questionnaires/tests
Other: Neuropsychiatric screening

Psychiatric diagnosis through:

  1. clinical interview
  2. the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), based on the SCID-I-NP (Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders-Non Patient Version);
  3. HAM-D (Hamilton Scale for Depression);
  4. PHQ-9 (Patient's Health Questionnaire-9 items);
  5. MDQ (Mood Disorders Questionnaire);
  6. YMRS (Young Mania Rating Scale);
  7. ASRM (Altman Self Rating Mania scale);

  8. BRIAN (Biological Rhythms Interview of Assessment in Neuropsychiatry).

    Assessment of Quality of Life:

  9. SF-12 (Short Form Health Survey-12 items).

Neuropsychological screening:

l) Addenbrooke's Cognitive Examination (ACE-R).
Neuropsychiatric screening (treatment-)
Subjects affected by chronic hepatitis HCV-related, in wait list for new antiviral drugs treatment, will be screened by psychiatric and neuropsychological questionnaires/tests
Other: Neuropsychiatric screening

Psychiatric diagnosis through:

  1. clinical interview
  2. the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), based on the SCID-I-NP (Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders-Non Patient Version);
  3. HAM-D (Hamilton Scale for Depression);
  4. PHQ-9 (Patient's Health Questionnaire-9 items);
  5. MDQ (Mood Disorders Questionnaire);
  6. YMRS (Young Mania Rating Scale);
  7. ASRM (Altman Self Rating Mania scale);

  8. BRIAN (Biological Rhythms Interview of Assessment in Neuropsychiatry).

    Assessment of Quality of Life:

  9. SF-12 (Short Form Health Survey-12 items).

Neuropsychological screening:

l) Addenbrooke's Cognitive Examination (ACE-R).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Short Form Health Survey-12 item (SF-12)
Time Frame: Baseline (T0), and change from baseline at three (T4) and six (T7) months
Self-report questionnaire that examines the following dimensions of well-being: vitality, physical function, physical pain, perception of general health, mental, physical, and emotional health, social role.
Baseline (T0), and change from baseline at three (T4) and six (T7) months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS)
Time Frame: Baseline (T0)
semi- structured interview to diagnose most of the psychiatric disorders, consistent with the diagnostic criteria of the DSM IV (Diagnostic and Statistical Manual of Mental Disorders, 4th ed.)
Baseline (T0)
Hamilton Scale for Depression (HAM-D)
Time Frame: Baseline (T0), and change from baseline at three (T4) and six (T7) months
clinical evaluation scale of the following depressive features: anxiety and somatization, suicidal thoughts, weight loss, cognitive disorders, activity problems, depressive retardation, sleep disturbances, and insight. It consists of 21 items, with scores from 0 to 3. Scoring 8-17 is indicative of mild depression; 18-24 moderate depression; a score> 25 indicates a severe depression.
Baseline (T0), and change from baseline at three (T4) and six (T7) months
Patient's Health Questionnaire-9 items (PHQ-9)
Time Frame: Baseline (T0), and change from baseline: at two (T1) and four (T2) weeks, two (T3), three (T4), four (T5), five (T6), and six (T7) months.
Self-report questionnaire based on the DSM IV Major Depressive Disorder Diagnostic Criteria, investigating the presence and severity in the previous 2 weeks of 9 depressive symptoms, such as depressed mood, anhedonia, sleep and food disorders, fatigue, difficulty concentrating, motor behavior disorders, loss of self-esteem, suicidal ideation; the cut-off for minor depressive disorder is represented by scores ≥5, the one for major depressive disorder by scores ≥10. The questionnaire can be administrated by phone.
Baseline (T0), and change from baseline: at two (T1) and four (T2) weeks, two (T3), three (T4), four (T5), five (T6), and six (T7) months.
Mood Disorders Questionnaire (MDQ)
Time Frame: Baseline (T0)
Self-report 17-item questionnaire for lifetime screening of bipolar spectrum disorders (Type I and II Bipolar Disorder), through DSM IV diagnostic criteria; the cut-off is for scores ≥7
Baseline (T0)
Young Mania Rating Scale (YMRS)
Time Frame: Baseline (T0), and change from baseline at three (T4) and six (T7) months
11-item questionnaire, evaluating the severity of manic/hypomanic symptoms (excitement, dysphoria, logorrhea, disorders of form and content of thought, sleep disturbances, aggression, appearance and clothing, insight). A score ≥12 suggests the presence of a manic/hypomanic episode
Baseline (T0), and change from baseline at three (T4) and six (T7) months
Altman Self Rating Mania Scale (ASRM)
Time Frame: Baseline (T0), and change from baseline: at two (T1) and four (T2) weeks, two (T3), three (T4), four (T5), five (T6), and six (T7) months.
self-administered 5-item scale that evaluates the presence and severity in the previous week of manic and hypomanic symptoms, such as manic/irritable mood, increased self-esteem, reduced need for sleep, loquacity, hyperactivity; a score ≥ 6 indicates a high likelihood of a manic or hypomanic episode. It can be administered by phone
Baseline (T0), and change from baseline: at two (T1) and four (T2) weeks, two (T3), three (T4), four (T5), five (T6), and six (T7) months.
Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN)
Time Frame: Baseline (T0), and change from baseline at three (T4) and six (T7) months
21-item questionnaires that investigates the difficulties in sleep, daily activities, social relationships, and nutrition, and how these difficulties relate to biological rhythms
Baseline (T0), and change from baseline at three (T4) and six (T7) months
Addenbrooke's Cognitive Examination (ACE-R)
Time Frame: Baseline (T0), and change from baseline at three (T4) and six (T7) months
short cognitive test, which evaluates five cognitive domains: attention/orientation, memory, verbal fluency, language, visual-spatial abilities. The test, with a maximum score of 100 and a mild cognitive impairment cut-off of 66, includes the Mini Mental State Examination (MMSE).
Baseline (T0), and change from baseline at three (T4) and six (T7) months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Azienda Ospedaliero Universitaria di Cagliari

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gioia Mura, Dr, Azienda Ospedaliero Universitaria di Cagliari
  • Study Chair: Mauro G Carta, Prof, Azienda Ospedaliero Universitaria di Cagliari

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 18, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 9, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PG/2015/16964

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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