Mental Ability Challenge Study in Adults With and Without HIV

February 21, 2019 updated by: Asante Kamkwalala, Vanderbilt University Medical Center

Cholinergic Correlates of Impaired Cognitive Ability in HIV-Associated Neurocognitive Disorders

It is estimated that by 2016, nearly 50% of HIV-positive individuals in the US will be aged 50 or older, and up to 60% of those will experience some degree of cognitive impairment as they age. The purpose of this study is to evaluate the contribution of the neuronal cholinergic receptor system to the cognitive impairments seen in adults aging with chronic HIV Infection. By using anti-cholinergic challenge drugs to reversibly "stress" cognitive functioning, the investigators hope to understand whether the presence of the HIV virus in the brain impairs the neural system necessary for normal cognition, more than would be expected from normal cognitive aging.

Study Overview

Detailed Description

This study is intended to evaluate the involvement of the neuronal cholinergic receptor system in the accelerated cognitive aging profile seen in adults living with chronic HIV-1 infection. It is estimated by the CDC that by the year 2016, nearly 50% of the US' HIV-positive population will be 50 or older. The HIV-1 virus is known to enter the CNS very rapidly after initial infection, and cause a pattern of persistent neural inflammation, which is deleterious to neurons and glia. This damage is believed to be the basis of cognitive impairment associated with long-term chronic HIV infection, known as HIV-Associated Neurocognitive Disorders (HAND). Successful introduction of Anti-Retroviral Treatment (ART) has greatly reduced the likelihood of progressing to the most severe category of HAND (HIV-Associated Dementia), however the mild and moderate forms (Asymptomatic Neurocognitive Impairment and Mild Neurocognitive Disorder, respectively) are still fairly common even in adults declared "virally suppressed", with little to no detectable peripheral viral DNA/RNA. Prior studies have shown that over the lifetime, more than 50% of adults diagnosed with HIV will experience some degree of cognitive impairment as they age. Some of these changes may be due to cholinergic dysfunction. The acetylcholinergic receptor system is necessary for normal cognitive performance, and is active during working memory, executive functioning, attention, and learning tasks. It has been shown that as the human brain ages, cognitive ability begins to decline, and correlates with declining acetylcholinergic activity. The cholinergic theory of cognitive aging postulates that this loss of activity at cholinergic receptors with age is at least partly responsible for poorer cognitive performance in aging. I will use this model to examine the impact of HIV infection on cholinergic system functioning. This study will use a well-established anti-cholinergic drug challenge model to evaluate cognitive performance in domains of cognitive functioning relevant to cholinergic functioning. Under conditions of temporary muscarinic or nicotinic blockade, or a combination of both, I aim to explore the contribution of putative cholinergic receptor dysfunction to the observed symptoms of HAND. I also intend to determine whether age and HIV-status interact to produce an accelerated pattern of cholinergic cognitive aging that would indicate that older adults with HIV are at higher risk for more rapid cognitive aging than HIV-negative individuals. If successful, the outcome of this study would support the future exploration of novel pro-cholinergic medications to treat cognitive symptoms of HAND, which may improve quality of life for adults living with chronic HIV infection, as they survive into old age.

Study Type

Observational

Enrollment (Actual)

22

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

HIV-Positive Healthy older adults and HIV-Negative Healthy older adults

Description

Inclusion Criteria:

  1. 35 years of age or older;
  2. HIV-Positive (must be on ART's for at least 6 months, most recent viral load (within 6 months) <50, CD4+ count >200, must be diagnosed HIV-positive at least 5 years) or HIV-Negative, At-Risk Individuals
  3. Able and willing to give written informed consent
  4. Negative urine pregnancy test
  5. Adequate visual and auditory acuity to allow neuropsychological testing.

Exclusion Criteria:

  1. Unmanaged HIV Infection, identified by no current medication regimen or the presence of one or more AIDS-defining conditions
  2. Fagerstrom cigarettes per day (CPD) score of '2' indicating heavy use of nicotine
  3. An ART regimen including a Protease Inhibitor Medication
  4. A documented history of cardiac disease or abnormal ECG at Screening
  5. Current alcohol or substance abuse, particularly intravenously
  6. Current use of psychoactive medications (antipsychotics, benzodiazepines, etc.)
  7. Current Axis I or Axis II psychiatric disorder
  8. History of myocardial infarction in the past year or unstable or severe cardiovascular disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HIV-Positive
Patients will be administered each of 4 possible treatments: high dose (5 mcg/kg) scopolamine, high dose (20 mg) mecamylamine, a low dose combination (2.5mcg/kg and 10 mg) of scopolamine and mecamylamine, or placebo.
2.5 or 5 mcg/kg of scopolamine via IV
10 or 20mg of mecamylamine orally
HIV-Negative
Patients will be administered each of 4 possible treatments: high dose (5 mcg/kg) scopolamine, high dose (20 mg) mecamylamine, a low dose combination (2.5mcg/kg and 10 mg) of scopolamine and mecamylamine, or placebo.
2.5 or 5 mcg/kg of scopolamine via IV
10 or 20mg of mecamylamine orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive Outcome - Lower verbal memory score
Time Frame: 2 hours
Cognitive performance will be more significantly impaired by study medications in HIV-positive participants relative to HIV-negative participants, indicating impairment of cholinergic neurotransmitter system.
2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Age and HIV-Status Interaction - Slower CRTreaction time
Time Frame: 2 hours
Older age and positive HIV status will interact to more significantly impair cognitive performance as measured by reaction time on the Choice Reaction Time task under the influence of study medications, than either variable alone.
2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2015

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

July 27, 2017

First Submitted That Met QC Criteria

August 4, 2017

First Posted (Actual)

August 9, 2017

Study Record Updates

Last Update Posted (Actual)

February 25, 2019

Last Update Submitted That Met QC Criteria

February 21, 2019

Last Verified

February 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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