30-to-90 Day Challenge: Effects of Alcohol Cessation on Health Outcomes

Effects of Experimentally-induced Reductions in Alcohol Consumption on Brain Cognitive and Clinical Outcomes, and Motivation for Changing Drinking in Older Persons With HIV Infection

The objective for this project is to determine whether how certain behavioral and health functions change in persons with heavy drinking when they stop (or reduce) drinking for 30 days, and whether changes continue for up to 90 days. The study will also identify barriers and facilitators related to drinking reduction. The project will focus on clinical comorbidities including HIV disease control, cognitive and brain function, liver abnormalities, and chronic inflammation. The study teams propose to enroll 140 HIV+ and 40 HIV- adults with heavy drinking, and then use Contingency Management (CM) with financial incentives to encourage participants to maximally reduce alcohol consumption for 30 days. Participants will be required to wear an ankle biosensor (SCRAM monitor) at all times, which is used to monitor participants' drinking behavior. At 30 days, participants will complete a full day of follow-up, including cognitive testing, neuroimaging, blood testing, liver Fibroscan, and questionnaires. Many participants will also provide a stool sample for gut microbiome assessment at each time point. At 30 days, participants will participate in a motivational interview to discuss perceived benefits and obstacles to drinking reduction, and most participants will continue CM to 90 days (but can opt out at this point). Participants will complete another full-day assessment at 90 days, at which point persons may choose to drink or not on their own (no more CM). A final assessment will be conducted at 12 months. This A-B-A design will enable us to clearly identify whether alcohol effects on cognition and brain function are reversible in the context of HIV, and analyze specific cerebral and systemic pathophysiological factors contributing to these effects. The inclusion of HIV- adults will enable subgroup comparisons of alcohol reduction effects in the context of HIV vs. no-HIV. These HIV-negative participants will be recruited from the same settings as our HIV+ participants, and will include a similar proportion by age, race, and gender as the HIV+ participants. The study team will use information from the MI data and our other assessments to elucidate factors that predict both short term (during CM) and long-term (1-year) alcohol reductions, and study how changes in alcohol consumption affect important HIV clinical outcomes that will be monitored over time.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Diseases; HIV Infections; Alcohol Drinking; Chronic Inflammation; Neurocognitive Dysfunction
• Intervention / Treatment: Behavioral: Contingency Management (CM)

Detailed Description

This proposed study continues a line of research by Doctors Cohen, Cook, Kahler, and colleagues on heavy alcohol use, HIV-associated brain dysfunction, and long-term HIV outcomes. The study will build on our past findings to determine the extent to which marked reductions in alcohol consumption at 30 days and again at 90 days via contingency management (CM) improves cognitive-behavioral performance, underlying brain functions and pathophysiology, and HIV-associated health outcomes. This feature in itself is a novel contribution and has rarely been done, but more importantly, it reflects the mission of the collaboration to develop actionable data on clinical trajectories in HIV infected heavy drinkers over age 50 that will instill high confidence in guiding next therapeutic steps. The study team will obtain a better understanding of how persons with HIV stop drinking, and what factors influence long-term drinking changes. These important clinical and scientific questions need resolution for successful treatment and management of HIV+ adults. This study is motivated by evidence that HIV-associated neurocognitive dysfunction continues despite effective combined anti-retroviral therapies (cART). Even mild cognitive impairments have detrimental functional effects and health outcomes that worsen as HIV+ people age. Heavy alcohol consumption is common among HIV+ adults, and contributes to functional brain disturbances directly or indirectly via systemic metabolic or inflammatory disturbances. However, our past findings indicate that current alcohol use is more strongly associated with cognitive and brain dysfunction among HIV+ adults than lifetime consumption; and that adverse brain effects occur primarily with heavy drinking. Our overarching hypothesis is that the impact of ongoing heavy alcohol use on the brain and cognition may be reversible, providing a strong impetus for the proposed study. The study team will conduct our research in Florida, which has the highest number of new HIV infections in the US, as well as an increasingly diverse population with HIV+, 50% of whom are now aged 50 years or over in the state.

Our research will seek to modify alcohol consumption by using contingency management (CM) and measure for changes in brain pathophysiology and function, as well as changes in systemic inflammation, and gut and liver pathologies which are hypothesized pathways by which alcohol may increase brain dysfunction. The study team will also measure neurocognitive functioning related to learning, attention-executive functions, working memory, and processing speed, domains in which HIV+ persons experience persistent impairment. the study team will use Motivational Interviewing (MI) to learn more about how persons with and without HIV reduce drinking, what factors are associated with long-term drinking changes, and how these drinking changes influence HIV clinical health behavior and outcomes. If the impact of alcohol on systemic and cerebral inflammation is temporary, then reducing or eliminating alcohol consumption could dramatically improve cognitive function and indices of brain health, even among people who have consumed alcohol for many years in the past. Our research will directly test hypotheses that ongoing heavy alcohol consumption is associated with brain pathophysiology and inflammation that impairs both functioning and cognitive processing, and that the inflammation and its sequelae are reversible in most HIV+ persons with alcohol cessation. The proposed sample will be 140 adults with HIV infection and 40 adults without HIV infection (at least 25% female; age >50 years). Participants will be recruited from heavy drinkers (>=14 drinks/week women, >=21 drinks/week men) with HIV infection identified from our ongoing Florida Cohort. HIV- participants will be recruited from community medical clinics where flyers will be posted.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women;
2. Age: 50-75 yrs.;
3. 140 participants will have confirmed HIV (confirmed via baseline bloodwork) and 40 participants will be HIV negative
4. English speaking (will have protocol ready in Spanish in 2017);
5. Physically mobile;
6. Willing to participate in CM to reduce alcohol consumption, and to wear the alcohol biosensor for at least 30 days. All participants will be current, heavy drinkers (>=14 drinks/week women, >=21 drinks/week men), confirmed by baseline timeline follow-back, and by having evidence of at least 3 drinking episodes on the alcohol biosensor prior to baseline). Must blow a "zero" on breathalyzer at time of informed consent

Exclusion Criteria:

1. Neurological disorders (e.g., dementia, stroke, seizures, traumatic brain injury).
2. Evidence of dementia (MOCA < 17).
3. Past opportunistic brain infection
4. Major psychiatric illness (schizophrenia, intractable affective disorder, current substance dependence diagnosis).
5. Current major psychiatric disturbance, including severe major depression.
6. Unstable medical conditions (e.g., cancer).
7. MRI contraindications (e.g., pregnancy, severe claustrophobia, metal implants).
8. Physical impairment precluding motor response or lying still.
9. Significant history of alcohol withdrawal as indicated by an Alcohol Withdrawal Symptom Checklist score ≥ 23 (within past year).
10. Unable to correctly answer a set of questions that demonstrate understanding of key aspects of the study, including the voluntary nature of the study, the purpose of the study, what participants are being asked to do as part of the study, and what are the risks related to participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Adults with or without HIV infection; Participants will be asked to stop drinking for at least 30 and up to 90 days. The study will use Contingency Management (CM) with financial incentives to encourage participants to maximally reduce alcohol consumption.	Behavioral: Contingency Management (CM); A reinforcement delivery method that involves financial incentive to participants for sustained alcohol abstinence. CM will start after the participants complete the baseline measures and last for at least 30 days and up to 90 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neurocognitive Functions	Change in cognitive performance from baseline to 30-day follow-up. NIH Toolbox Cognition Battery is administered by a research assistant and consists of seven tests assessing memory, attention, cognitive flexibility, processing speed, and executive functioning. Summary scores will be calculated.	Baseline, 30 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neuroinflammation	Change in brain inflammation from baseline to 30-day follow-ups. Neuroinflammation is measured by cerebral metabolic neuroinflammatory markers, which include Magnetic Resonance Spectroscopy (MRS) metabolite concentrations (Cho and Myo-Inositol) and extracellular free water from Diffusor Tension Imaging sequences (DTI-FW).	Baseline, 30 Days
Change in Brain Function	Change in Brain Function from baseline to 30-day follow-up. Brain function is measured by mean signal intensity for specific task-dependent brain regions from functional magnetic resonance imaging (fMRI).	Baseline, 30 Days
Change in markers of systemic Inflammation	Blood testing for biomarkers of systemic inflammation such as cytokines, ceramides, FIB-4, and marker of abnormal liver function.	30 Days
Change in liver Status	Evidence of liver fibrosis, fatty liver, and liver inflammation as measured by fibroscan	30 Days
Change in Drinks/week in the Past 30 Days	Change in number of standard drinks per week in the past 30 days from baseline to 1 year follow-up, calculated from Timeline Follow Back (TLFB) interview.	Baseline, 1 Year
Change in gut microbiome	Change in the ratio of Firmicutes: Bacteriodetes ratio, and change in the relative abundance of Proteobacteria	Baseline, 30-days, 90-days, 1 year

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); University of Miami; Brown University; Florida International University
• Investigators: Principal Investigator: Robert Cook, University of Florida; Principal Investigator: Ronald Cohen, University of Florida

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 11, 2017
• Primary Completion (ACTUAL): August 1, 2022
• Study Completion (ANTICIPATED): August 1, 2023

Study Registration Dates

• First Submitted: November 3, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (ACTUAL): November 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Digestive System Diseases; Pathologic Processes; Drinking Behavior; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Neurocognitive Disorders; Cognition Disorders; Slow Virus Diseases; Liver Diseases; Alcohol Drinking; HIV Infections; Inflammation; Infections; Cognitive Dysfunction; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: CED000000011-N; U01AA020797-06 (NIH); U01AA026225 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Limited and de-identified datasets will be available to researchers after signing a data-use agreement with the University of Florida.
• IPD Sharing Time Frame: Our documents can be shared once the study begins. Data sharing will be an option for at least 5 years after the study is completed.
• IPD Sharing Access Criteria: Contact the principal investigator. In the future, information about how to request data will be on a public website
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No