Cerebral Effects of Pegylated Interferon in Hepatitis C Positive Subjects

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00136214
• Other study ID #: 2003P000341
• Status: Completed
• Start date: March 2004
• Est. completion date: March 2008

Study information

• Verified date: June 2018
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: March 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Diagnostic Test:
• MR brain and neuropsychiatric tests

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Schering-Plough

Country where clinical trial is conducted

United States, 

References & Publications (1)

Byrnes V, Miller A, Lowry D, Hill E, Weinstein C, Alsop D, Lenkinski R, Afdhal NH. Effects of anti-viral therapy and HCV clearance on cerebral metabolism and cognition. J Hepatol. 2012 Mar;56(3):549-56. doi: 10.1016/j.jhep.2011.09.015. Epub 2011 Oct 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Primary	Neurocognitive Tests for Cerebral Function	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