Cerebral Effects of Pegylated Interferon in Hepatitis C Positive Subjects

June 20, 2018 updated by: Nezam H. Afdhal, Beth Israel Deaconess Medical Center

A Study of the Cerebral Effect of Pegylated Interferon in Hepatitis C Positive Subjects

The hypothesis of this study is that pegylated interferon would cause cognitive deficits and mood changes in hepatitis C (HCV) positive subjects.

Study Overview

Status

Completed

Conditions

Detailed Description

Subjects with non-cirrhotic hepatitis C will have a magnetic resonance imaging (MRI)/magnetic resonance (MR) spectroscopy and neuropsychological testing prior to starting interferon. Subjects will have repeat testing following 12 weeks of interferon therapy and again at 12 weeks post interferon therapy.

MR spectroscopy (MRS) will measure the cerebral metabolites, NAA (N-acetyl aspartate), Cho (choline), MI (myoinositol) and Cr (creatine) at 3 distinct brain regions, i.e. basal ganglia and 2 locations within the frontal cortex.

Neuropsychological testing will include tests of the following cognitive domains: executive functioning, memory, language, motor skills and will also include questionnaires pertaining to quality of life (SF-36), mood (Beck's depression inventory) and a self-rating cognitive questionnaire (Conners' Adult Attention Deficit Hyperactivity Disorder Rating Scales [CAARS]).

Control subjects will include non-cirrhotic HCV subjects who are not taking interferon therapy.

Study Type

Observational

Enrollment (Actual)

22

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

    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center

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

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

HCV positive patients Subjects with cirrhosis, active alcohol or drug abuse, co-infection with human immunodeficiency virus (HIV), structural brain abnormality, past history of cerebrovascular accident (CVA), serious head trauma, and seizure disorder were excluded. Other exclusions were contraindication to PIFN therapy, current psychiatric disorder or contraindications to MRI e.g., pacemaker and claustrophobia.

Description

Inclusion Criteria:

  • Adults (>18 years old) of both sexes with chronic HCV infection (all genotypes).
  • Subjects due to start treatment with pegylated interferon-alpha (IFN-a) for HCV eradication.
  • Subjects with chronic hepatitis C who have elected not to be treated with pegylated-IFN-a
  • Subjects with mild fibrosis on liver biopsy (stage 0-III/IV fibrosis)
  • Subjects able to give informed consent.
  • Subjects with controlled depression currently taking anti-depressant medication.

Exclusion Criteria:

  • Subjects with cirrhosis on liver biopsy.
  • Subjects with active alcohol or drug abuse.
  • Subjects co-infected with human immunodeficiency virus (HIV).
  • Subjects with structural brain abnormality, past history of cerebrovascular accident (CVA) or serious head trauma.
  • Subjects with seizure disorder.
  • Subjects with any contraindication to IFN therapy.
  • Subjects with a poor command of the English language.
  • Subjects with a contraindication to MRI, e.g. pacemaker, claustrophobia.

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
Intervention / Treatment
Interferon Treated Group
Group treated with PEG-Interferon and ribavirin and undergoing MR brain and neuropsychiatric tests
Non-treated cohort control
Group undergoing MR brain and neuropsychiatric tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ratios of Cerebral Metabolites Choline (CH), Myoinisitol (MI) and N-acety Aspartate (NAA)to Creatine (Cr) in 3 Brain Regions Including Basal Ganglia, Frontal Cortex and Left Dorsolateral Prefrontal Cortex
Time Frame: 18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline
Evaluation of changes in MR spectroscopy. reductions in ratio of Cho and MI reflect improvements in cerebral inflammation and improvement in cognition. Increases in the NAA ratio are suggestive of improvement in cognitive function.
18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline
Neurocognitive Tests for Cerebral Function
Time Frame: 18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline and only done in treated group and not controls
A battery of pen and paper neurocognitive tests where subject means are reported compared to the normative Z score. Data is reported at baseline (T1), week 12 on treatment (T2) and 12 weeks after treatment (week 60, T3). Improvements are increases in the test result compared to baseline as determined against the Z score. tests performed included Hopkins learning trials (HVLT), a measure of of verbal learning and memory and the Roy-Osterrieth Complex figure test (ROCF) which evaluates visio-spatal abilities, memory, planning and working memory. Improvements in the score (increases in value compared, either less negative or more positive to the Z score) shown in the table are reflective of improvements in these neurocognitive parameters.
18 months overall with measures performed at baseline (T1), week 12 (T2) and 12 weeks after end of treatment (T3) with PEG-IFN for 48 weeks which is 60 weeks post baseline and only done in treated group and not controls

Collaborators and Investigators

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

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.

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

March 1, 2004

Primary Completion (Actual)

January 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

August 25, 2005

First Submitted That Met QC Criteria

August 26, 2005

First Posted (Estimate)

August 29, 2005

Study Record Updates

Last Update Posted (Actual)

July 12, 2018

Last Update Submitted That Met QC Criteria

June 20, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

Clinical Trials on Hepatitis C

Clinical Trials on MR brain and neuropsychiatric tests

3
Subscribe