HIV-1 and Brain Interaction on Smoking Comorbidity

People living with HIV-1 have high rates of cigarette smoking, which may be related to nicotinic interaction with HIV-1 infection and brain function levels. The proposed project aims to understand these pathways using translational brain imaging and HIV-1 reactivation studies. The study proposes a targeted nicotine-brain investigation of the nicotinic effects in HIV-1 infection from cellular to brain circuitry levels.

Study Overview

• Status: Withdrawn
• Conditions: Smoking
• Intervention / Treatment: Other: Tobacco smoking and nicotine patch

Detailed Description

Smoking remains the leading cause of preventable morbidity and mortality in the United States. The alarmingly high smoking rates and unsatisfactory performance of standard smoking cessation efforts in people living with HIV/AIDS (PLWH) interfere with the overall progress in the treatment of HIV-1 infection. Our understanding of nicotine addiction mechanisms in PLWH, and how they are related to and interact with HIV-1 neuropathology, is limited and thus hindering the development of more effective, targeted treatments. The study will directly address neurological complication of this HIV-associated comorbidity at the brain circuitry level using state-of-the-art imaging tools and methods.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21228
      • University of Maryland School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects between ages 18-60 in good health
2. Ability to give written informed consent
3. For people living with HIV: should be diagnosed with HIV two years or more and on ART two years or more
4. For people living with HIV: should have achieved virologic suppression (defined as viral loads of ≤ 200 copies/ml), and without current signs of reactivation

Exclusion Criteria:

1. Inability to sign informed consent
2. Unable to undergo MRI scanning due to metallic devices or objects (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts) or claustrophobic to the scanner
3. Any major medical illnesses to include, but not limited to, uncontrolled high blood pressure or high blood sugar, cardiovascular disease, asthma, peripheral vascular diseases, coagulopathies, history of superficial or deep vein thrombosis as per medical history
4. Current substance-induced psychiatric disorders
5. Significant alcohol or other drug use, other than nicotine dependence or marijuana use
6. Gross structural abnormalities and/or have a history of syncope
7. Positive urine pregnancy tests
8. Any neurological illnesses to include, but not limited to, seizure disorders, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS tumor,
9. For people living with HIV: having AIDS or non-AIDS-defining cancer or active CNS and other opportunistic disease
10. For people living with HIV: on active treatment of hepatitis C virus (HCV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV-1 smokers	Other: Tobacco smoking and nicotine patch; Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use
No Intervention: HIV-1 nonsmokers
Active Comparator: Healthy control smokers	Other: Tobacco smoking and nicotine patch; Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use
No Intervention: Healthy control nonsmokers
Active Comparator: HIV-1 nonsmokers using nicotine patch	Other: Tobacco smoking and nicotine patch; Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use
No Intervention: HIV-1 nonsmokers using placebo patch
Active Comparator: Healthy control nonsmokers using nicotine patch	Other: Tobacco smoking and nicotine patch; Tobacco smoking at each participant's regular cigarette. Over-the-counter nicotine patch use
No Intervention: Healthy control nonsmokers using placebo patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional and structural connectivity using magnetic resonance imaging (MRI)	Resting functional MRI and diffusion imaging MRI	one day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV-1 reactivation	HIV-1 viral protein p24 expression	one day

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): October 30, 2025
• Study Completion (Anticipated): October 30, 2025

Study Registration Dates

• First Submitted: October 7, 2017
• First Submitted That Met QC Criteria: October 7, 2017
• First Posted (Actual): October 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 10, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: HIV; smoking; brain; nicotine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: HP-00075780

Drug and device information, study documents

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