Clinical trial NCT00136214: Cerebral Effects of Pegylated Interferon in Hepatitis C Positive Subjects
Official title: A Study of the Cerebral Effect of Pegylated Interferon in Hepatitis C Positive Subjects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2005-08-29
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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
measure: Neurocognitive Tests for Cerebral Function
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Nezam Afdhal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.