HIV-1-infectionNCT03244488
Mental Ability Challenge Study in Adults With and Without HIV
An observational study of HIV-1-infection and Aging, Premature, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV-1-infection, Aging, Premature, Cognitive Impairment
- What is being tested?
- Scopolamine Injectable Product and Mecamylamine Pill
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 35 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: HIV-Positive Healthy older adults and HIV-Negative Healthy older adults
Who may be able to join
- 35 years of age or older;
- 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
- Able and willing to give written informed consent
- Negative urine pregnancy test
- Adequate visual and auditory acuity to allow neuropsychological testing.
Who cannot join
- Unmanaged HIV Infection, identified by no current medication regimen or the presence of one or more AIDS-defining conditions
- Fagerstrom cigarettes per day (CPD) score of '2' indicating heavy use of nicotine
- An ART regimen including a Protease Inhibitor Medication
- A documented history of cardiac disease or abnormal ECG at Screening
- Current alcohol or substance abuse, particularly intravenously
- Current use of psychoactive medications (antipsychotics, benzodiazepines, etc.)
- Current Axis I or Axis II psychiatric disorder
- History of myocardial infarction in the past year or unstable or severe cardiovascular disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
About this study
Official title: 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.
Read the 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
- Being tested
- Scopolamine Injectable Product, Mecamylamine Pill
- Medical subject headings
- Aging, Premature, Cognitive Dysfunction, Memory Disorders, AIDS Dementia Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Scopolamine Injectable ProductDrug
2.5 or 5 mcg/kg of scopolamine via IV
Mecamylamine PillDrug
10 or 20mg of mecamylamine orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Scopolamine Injectable Product; Drug: Mecamylamine Pill | |
| 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. Receives: Drug: Scopolamine Injectable Product; Drug: Mecamylamine Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Outcome - Lower verbal memory score
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.
Measured: 2 hours
Secondary outcomes (1)
Age and HIV-Status Interaction - Slower CRTreaction time
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.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2017
- Study startDec 2015
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Cross-sectional
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asante Kamkwalala, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03244488
- Sponsor's protocol ID
- 150929
- Status last verified
- Feb 2019
- First submitted
- 27 Jul 2017
- Last updated
- 25 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholinergic Correlates of Impaired Cognitive Ability in HIV-Associated Neurocognitive Disorders
- ClinicalTrials.gov ID
- NCT03244488
- Acronym / sponsor ID
- 150929
- Conditions
- HIV-1-infection, Aging, Premature, Cognitive Impairment, Memory Impairment, HIV-Associated Cognitive Motor Complex
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 9 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case crossover
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV-Positive | – | Drug: Scopolamine Injectable Product, Drug: Mecamylamine PillPatients 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. |
| HIV-Negative | – | Drug: Scopolamine Injectable Product, Drug: Mecamylamine PillPatients 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. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-Positive Healthy older adults and HIV-Negative Healthy older adults
Key inclusion criteria (5 listed)
- 35 years of age or older;
- 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
- Able and willing to give written informed consent
- Negative urine pregnancy test
- Adequate visual and auditory acuity to allow neuropsychological testing.
Key exclusion criteria (8 listed)
- Unmanaged HIV Infection, identified by no current medication regimen or the presence of one or more AIDS-defining conditions
- Fagerstrom cigarettes per day (CPD) score of '2' indicating heavy use of nicotine
- An ART regimen including a Protease Inhibitor Medication
- A documented history of cardiac disease or abnormal ECG at Screening
- Current alcohol or substance abuse, particularly intravenously
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Scopolamine Injectable Product2.5 or 5 mcg/kg of scopolamine via IV | Drug | HIV-Negative, HIV-Positive |
| Mecamylamine Pill10 or 20mg of mecamylamine orally | Drug | HIV-Negative, HIV-Positive |
Primary outcome
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.
1 secondary outcome
Age and HIV-Status Interaction - Slower CRTreaction time
Time frame: 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection and Aging, Premature, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Outcome - Lower verbal memory score (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2019.