Clinical trial NCT02650024: Impact of Hepatitis C Virus Therapy on Central Nervous System Outcomes
Official title: Impact of Hepatitis C Virus Therapy on Central Nervous System Outcomes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C
Human Immunodeficiency Virus
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2016-01-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 75% of subjects will be male and 25% female. Based on the nature of the HCV clinics where the cohort will be largely recruited, we expect to enroll approximately 25-30% Hispanics, 15-20% African Americans, 2-5% Asian-Pacific Islanders, and 50% non-Hispanic whites.

Brief summary: This study observes the effects of newly developed direct-acting antiviral (DAA) treatments on the central nervous system (CNS) of individuals with chronic Hepatitis C (HCV). The goals of this study are to determine the CNS impact of curing chronic HCV disease with newly established DAA therapies and how HIV alters this relationship.

Detailed description: The specific aims of the study are as follows:

Aim 1. Impact of HCV Cure on CNS Outcomes. Determine how curing HCV without IFN alters CNS outcomes in substance users with chronic HCV disease.

Aim 2. Correlates of CNS Outcomes. Determine the viral and host correlates of Aim 1's neurocognitive outcomes.

Aim 3. Impact of HIV Co-infection. Explore how HIV alters the relationships observed in Aims 1 and 2. Hypothesis 3: Compared with HCV mono-infected adults, SVR will be less likely to result in improved CNS outcomes in HCV/HIV co-infected adults.

Eligibility criteria: About 40 HCV+ and HCV/HIV co-infected patients with neurocognitive impairment (NCI) and a history of substance abuse will take part in this study.

INCLUSION CRITERIA

1. Adults (18 years old or older) with chronic HCV and NCI with a GDS greater than or equal to 0.35 (n=40).
2. Presence of chronic HCV infection based on chart review will be defined as positive for anti-HCV antibody or HCV RNA at least 6 months before screening.
3. Plan to receive HCV treatment from their primary care physician within 1 month of enrollment.
4. For the HIV/HCV co-infected group only, subjects must have HIV. HIV status will be obtained through self-report. Self-report will be confirmed at the pretreatment visit using a HIV-1 point of care test. In the event that point of care test and self-report are discordant, then HIV status will be confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV-1 and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load.

EXCLUSION CRITERIA

1. Cirrhosis or bridging fibrosis (mHAI stages 4-6 or its equivalent).

   * Liver biopsy at any time showing mHAI stage 4 or higher fibrosis OR
   * FibroScan within 12 months demonstrating liver stiffness of ≥9.5 kPa OR
   * APRI ≥2.0 and FIB-4 ≥3.25
   * NOTE: If APRI and FIB-4 are discordant one of the other forms of fibrosis staging must be used.
2. Any cause of liver disease other than chronic HCV infection, including but not limited to the following:

   * Hemochromatosis
   * Alpha-1 antitrypsin deficiency
   * Wilson's disease
   * Autoimmune hepatitis
   * Alcoholic liver disease
   * Drug-related liver disease
3. Severe NC confounding conditions (stroke, head injury, or developmental learning disability).
4. Regular use of anti-inflammatory drugs.
5. Current or recent treatment with pegylated interferon (PEG-IFN).
6. Other active inflammatory process (major infection, malignancy, rheumatoid arthritis/autoimmune disorder) within the prior 28 days.
7. Uncontrolled or active depression or other psychiatric disorder that in the opinion of the site investigator might preclude adherence to study requirements or impact NC functioning and assessments.
8. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
9. Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry.

Primary outcomes:
measure: Number of participants with change in neurocognitive impairment defined by Global Deficit Score (GDS) > or equal to 0.5 related to HCV treatment
timeFrame: 5 years
Secondary outcomes:
measure: Number of participants with abnormal laboratory values representing viral and host factors related to HCV treatment
timeFrame: 5 years
measure: Number of HIV-infected participants with abnormal laboratory values representing viral and host factors related to HCV treatment
timeFrame: 5 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Ucsd Hnrp
state: California
Study officials:
affiliation: UCSD
name: Ajay Bharti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: