HCV and Co-morbid Alcohol Use Disorders: A Translational Investigation of Antiviral Therapy Outcomes on CNS Function

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 21 years and older
• All sexes
• Healthy volunteers accepted
• Adult, Older adult

Study population: Adult Veterans (> 21 years old) who are about to initiate DAA therapy for HCV are recruited into two demographically matched (i.e., similar in terms of age, gender, race, and years of education) groups (n = 30/group): 1) adults with current alcohol use disorder (AUD+/HCV+) and 2) adults without current AUDs (AUD-/HCV+). Two additional groups of demographically-matched adults: 1) without AUD or HCV (AUD-/HCV-) (n = 30), and 2) with AUD and no HCV (AUD+/HCV-) will be recruited as a comparison groups to determine the relative contribution of a history of HCV infection to alcohol-induced brain pathology.

Trial locations and contacts

1 site in 1 country.

About this study

Conditions

Hepatitis C, Alcohol Use Disorder

Being tested

Neuropsychological assessment, Neuroimaging

Keywords

Hepatitis C, Direct-acting antiviral therapies, DAA, Chronic HCV infection, Alcohol Use Disorder

Medical subject headings

Hepatitis C, Alcoholism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Neuropsychological assessmentDiagnostic test

  Clinical research staff will complete a standardized neuropsychiatric study visit protocol with eligible participants who provide informed consent. The protocol will be conducted twice for each participant (baseline and 6 months later).

• NeuroimagingBehavioural

  Subjects, well characterized with respect to their substance use, will be evaluated with functional magnetic resonance imaging (fMRI) tasks, resting state MRI (rsMRI), high resolution anatomical MRI, standard diffusion weighted imaging (DWI) and high angular resolution diffusion imaging (HARDI) at baseline and 6 months later.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Changes in Neuropsychological Assessment Battery (NAB) Attention Module Scores

   The Attention Module is a marker of attentional capacity, working memory, and processing speed. T-scores are derived by converting raw scores using normative tables that account for age and education. T-scores range from 20 to 80 with a mean of 50 and standard deviation of 10. Lower T-scores (below 40) indicate below average performance and higher T-scores (above 60) indicate above-average performance. NAB Attention Module subtests include: Dots, Numbers and Letters, Driving Scenes, Digits Forward, and Digits Backward. Subtest scores were averaged to compute a total score. Change was calculated as the value at 6 months minus the value at baseline. Larger numbers represent greater improvement in attention performance, a score of 0 indicates no change in performance and negative numbers indicate a worsening of attention performance over time.

   Measured: Baseline and 6 months

2. Changes in Neuropsychological Assessment Battery (NAB) Memory Module Scores

   The Memory Module is a marker of learning, recall, and recognition memory. T-scores are derived by converting raw scores using normative tables that account for age and education. T-scores range from 20 to 80 with a mean of 50 and standard deviation of 10. Lower T-scores (below 40) indicate below average performance and higher T-scores (above 60) indicate above-average performance. NAB Memory Module subtests include: List Learning, Shape Learning, Story Learning, and Daily Living Memory. Subtest scores were averaged to compute a total score. Change was calculated as the value at 6 months minus the value at baseline. Larger numbers represent greater improvement in memory performance, a score of 0 indicates no change in performance and negative numbers indicate a worsening of memory performance over time.

   Measured: Baseline and 6 months

3. Changes in Neuropsychological Assessment Battery (NAB) Executive Functions Module Scores

   The Executive Functions Module of the NAB is a marker of executive function, including problem-solving and mental flexibility. T-scores are derived by converting raw scores using normative tables that account for age and education. T-scores range from 20 to 80 with a mean of 50 and standard deviation of 10. Lower T-scores (below 40) indicate below average performance and higher T-scores (above 60) indicate above-average performance. NAB Executive Function Module subtests include: Mazes, Judgement, Categories, and Word Generation. Subtest scores were averaged to compute a total score. Change was calculated as the value at 6 months minus the value at baseline. Larger numbers represent greater improvement in executive function performance, a score of 0 indicates no change in performance and negative numbers indicate a worsening of executive functioning performance over time.

   Measured: Baseline and 6 months

4. Changes in Alcohol Use Measured Using the Timeline Follow Back (TLFB)

   This outcome measure evaluates the change in the number of days of alcohol use from baseline to a 6-month follow-up, using the 30-Day Timeline Followback (TLFB) method. The TLFB is a structured, retrospective interview technique that allows participants to accurately recall their alcohol consumption patterns over the previous 30 days. For this outcome, the number of days on which alcohol was consumed will be assessed at baseline (the start of the study) and again at the 6-month follow-up assessment. A positive change would indicate an increase in the number of days of alcohol use, while a negative change would indicate a reduction in the number of days of alcohol use over the 6-month period.

   Measured: Baseline and 6 months

5. Change in Behavior as Assessed by the Balloon Analogue Risk Task (BART)

   The BART is a computerized measure of risk-taking behavior that concurrently measures several domains (i.e., risky decision-making, reward/negative outcome processing) during fMRI scanning.

   The ratio of balloon pumps made to maximum pumps allowed is a measure of risk-taking behavior. A ratio of 1 indicates that a participant inflated the balloon to its maximum allowed pumps, while a ratio closer to 0 suggests that the participant was much more conservative in their approach. Change was calculated as the value at 6 months minus the value at baseline and ranges from -1 to 1. A positive change indicates an increase in risk-taking behavior and a negative change indicates a decrease in risk-taking behavior over time.

   Measured: Baseline and 6 months

6. Change in Behavior as Assessed by the Monetary Incentive Delay (MID) Task

   The MID is a validated task to examine anticipatory brain responses to reward during fMRI scanning.

   This outcome measure evaluates the change in reaction time (RT) of participants in response to monetary reward cues during the MID. Reaction time is defined as the duration (in milliseconds) from the presentation of the cue to the participant's response (e.g., button press). The MID involves various reward conditions, including different monetary values and probabilities, allowing for an evaluation of participants' anticipatory responses to potential rewards. A positive difference indicates an increase in RT at 6-months compared to baseline, suggesting potential decreases in motivation, cognitive load, or changes in reward sensitivity. Conversely, a negative difference indicates a decrease in reaction time, which may reflect improved motivation, enhanced cognitive processing speed, or increased responsiveness to monetary incentives over time.

   Measured: Baseline and 6 months

7. Change in Fatigue Severity Scale (FSS) Score

   The Fatigue Severity Scale (FSS) is a 9-item self-report questionnaire designed to measure level of fatigue. The FSS is graded on a 7-point Likert-like scale ranging from 1 ("strongly disagree") to 7 ("strongly agree"). The score for all 9 items is summed to constitute the FSS score. The minimum FSS score is 7 and the maximum score possible is 63. A higher score represents greater fatigue severity. Change was calculated as the value at 6 months minus the value at baseline and reported here. A higher positive score indicates an increase in fatigue symptoms at 6 months compared to baseline, a lower negative score would indicate a decrease in fatigue symptoms over 6 months and a score of 0 would indicate no change in fatigue symptoms over 6 months.

   Measured: Baseline and 6 months

8. Change in Beck Depression Inventory Second Edition (BDI-II) Score

   The Beck Depression Inventory Second Edition (BDI-II) is a 21-question multiple-choice self-report inventory that measures depression. There is a four-point scale for each item ranging from 0-3. The total score can range from 0 to 63 points. Higher scores reflect a great level of depression severity.

   Measured: Baseline and 6 months

9. Change in Fractional Anisotropy (FA) in White Matter Tracts

   MRI-based diffusion tensor imaging (DTI) tractography is used to measure fractional anisotropy (FA), an indicator of CNS microstructural integrity. Increases in FA may reflect enhanced fiber organization or myelination, while decreases often indicate demyelination, axonal loss, or reduced coherence of white matter tracts.

   The JHU white-matter tractography atlas was used to extract FA values from 20 structures. Percent change was calculated. A positive number indicates an increase in FA after 6 months and a negative number indicates a decrease in FA from baseline to 6 months.

   Measured: Baseline and 6 months

10. Change in Mean Diffusivity (MD) in White Matter Tracts

    MRI-based diffusion tensor imaging (DTI) tractography is used to measure mean diffusivity (MD), which is the average rate of water diffusion in all directions within brain tissue. An increase in MD often indicates microstructural disruption, such as axonal loss, demyelination, or increased extracellular space due to edema or atrophy and decreases in MD can reflect cellular proliferation or restricted diffusion, as seen in certain types of gliosis or inflammatory conditions.

    The JHU white-matter tractography atlas was used to extract MD values from 20 structures. Percent change was calculated. A positive number indicates an increase in MD after 6 months and a negative number indicates a decrease in MD from baseline to 6 months.

    Measured: Baseline and 6 months

11. Changes in Inflammatory Profile Markers: Neutrophil to Lymphocyte Ratio (NLR) and Monocyte to Lymphocyte Ratio (MLR)

    Change was calculated as the value at 6 months minus the value and baseline. A positive number indicates an increase in inflammatory markers in plasma samples and a negative value indicates a decrease in inflammatory markers at 6 months.

    Measured: Baseline and 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted4 Apr 2019
2. Study start16 May 2019
3. Primary completion31 Oct 2023
4. Study completion29 Dec 2023

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Hepatitis CStudies of the same condition, open and under way.
• More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.