Mental Ability Challenge Study in Adults With and Without HIV

NCT ID: NCT03244488

Last Updated: 2019-02-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 22 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2018-12-31

Brief Summary

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.

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.

Conditions

HIV-1-infection; Aging, Premature; Cognitive Impairment; Memory Impairment; HIV-Associated Cognitive Motor Complex

Study Design

• Observational Model Type: CASE_CROSSOVER
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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.

Scopolamine Injectable Product

Intervention Type: DRUG

2.5 or 5 mcg/kg of scopolamine via IV

Mecamylamine Pill

Intervention Type: DRUG

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.

Scopolamine Injectable Product

Intervention Type: DRUG

2.5 or 5 mcg/kg of scopolamine via IV

Mecamylamine Pill

Intervention Type: DRUG

10 or 20mg of mecamylamine orally

Interventions

Scopolamine Injectable Product

2.5 or 5 mcg/kg of scopolamine via IV

Intervention Type: DRUG

Mecamylamine Pill

10 or 20mg of mecamylamine orally

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Asante Kamkwalala

Graduate Research Assistant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

150929

Identifier Type: -

Identifier Source: org_study_id