- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03244488
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
Status
Completed
Conditions
Intervention / Treatment
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:
- 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.
Exclusion Criteria:
- 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
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
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Neurocognitive Disorders
- Dementia
- HIV Infections
- AIDS Dementia Complex
- Aging, Premature
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Antiemetics
- Gastrointestinal Agents
- Adjuvants, Anesthesia
- Mydriatics
- Ganglionic Blockers
- Nicotinic Antagonists
- Mecamylamine
- Scopolamine
- Butylscopolammonium Bromide
Other Study ID Numbers
- 150929
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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.
Clinical Trials on Cognitive Impairment
-
University of California, San FranciscoNational Institute on Aging (NIA)RecruitingMild Cognitive Impairment | Cognitive Decline | Cognitive Deterioration | Cognitive Impairment, Mild | Cognitive Deficits, MildUnited States
-
Stanford UniversityRecruitingMild Cognitive Impairment | Subjective Cognitive ImpairmentUnited States
-
Fondazione Don Carlo Gnocchi OnlusUniversity of Florence; Consorzio di Bioingeneria e Informatica Medica; Gutenberg...CompletedCognitive Dysfunction | Mild Cognitive Impairment | Vascular Cognitive ImpairmentItaly
-
University of California, Los AngelesCompletedMild Cognitive Impairment (MCI) | Age-associated Cognitive ImpairmentUnited States
-
Universidad de ZaragozaNot yet recruitingMild Cognitive Impairment | Randomized Controlled Trial | Subjective Cognitive Impairment
-
BaycrestCentre for Aging and Brain Health InnovationUnknownNeurocognitive Disorders | Cognitive Dysfunction | Mental Disorder | Cognitive Impairment, Mild | Cognitive Disorder | Nonamnestic Mild Cognitive ImpairmentCanada
-
Region SkaneLund University; Berry LabCompletedMemory Impairment | Cognitive Impairment, MildSweden
-
University of GeorgiaApplied Universal Dynamics, Corp.; Van Robotics, Inc.Active, not recruitingRobot-assisted Cognitive Training for Lonely Older Adults With Mild Cognitive Impairment (MCI) (MCI)Cognitive Change | Aging | Cognitive Impairment, MildUnited States
-
University of HawaiiRecruitingMild Cognitive Impairment | Subjective Cognitive ImpairmentUnited States
-
Dr. Frances ChungRecruitingCognitive Impairment (CI)Canada
Clinical Trials on Scopolamine Injectable Product
-
Psoriasis Treatment Center of Central New JerseySun Pharmaceutical Industries LimitedUnknown
-
Tang-Du HospitalRecruitingMyasthenia Gravis, GeneralizedChina
-
Hospital Israelita Albert EinsteinMinistry of Health, BrazilCompletedSpinal Muscular AtrophyBrazil
-
National Taiwan University HospitalCompletedHepatitis A | Human Immunodeficiency Virus | Vaccine Response ImpairedTaiwan
-
Assiut UniversityCompletedOsteoarthritis Knees BothEgypt
-
University of VirginiaRegeneron PharmaceuticalsRecruiting
-
Cairo UniversityUnknown
-
Mercy Medical CenterRecruitingHepatitis B | Cirrhosis, Liver | Chronic Liver DiseaseUnited States
-
Nova Scotia Health AuthorityDalhousie UniversityActive, not recruiting