Healthy AgingPhase 1NCT03408574
The Nicotinic Cholinergic System and Cognitive Aging
A Phase 1 study of Healthy Aging, run by University of Vermont at 1 site in United States.
Trial summary
Prior research has shown that a chemical system in the brain called the cholinergic system is primarily responsible for cognitive symptoms seen in people with dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and a subset of receptors… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Aging
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2016to 31 Jan 2022
- Phase
- Phase 1
- 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Normal cognition, not demented, no mild cognitive impairment. IQ greater than 80.
Who cannot join
- Current use of barbiturates, rifampin, insulin, carbamezepine, oral hypoglycemics, antidepressants, diabetes, or untreated thyroid disease.
- In addition, the following exclusions are specific for the challenge drugs: heavy alcohol or coffee use, significant cardiovascular disease, ischemic heart disease, asthma, chronic obstructive pulmonary disease, active peptic ulcer, hyperthyroidism, pyloric stenosis, narrow angle glaucoma, epilepsy, or current Axis I psychiatric disorders.
- Current use of centrally active drugs and drugs with cholinergic properties. A minimum of 14 days will elapse between discontinuing centrally active or psychoactive agents and this study.
Trial locations and contacts
1 site in 1 country.
About this study
Prior research has shown that a chemical system in the brain called the cholinergic system is primarily responsible for cognitive symptoms seen in people with dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and a subset of receptors called the nicotinic system plays in cognition in healthy non-demented older adults (referred to as normal cognitive aging). This is critical because the ever growing healthy aging population will show declines in cognition that fall short of dementia but still impact functional abilities and independence. Maintaining good nicotinic system functioning throughout adulthood may lessen the cognitive symptoms of aging. At this time, it is not clear what the biological cause of age-related changes in cognition is. This study will examine the role of the nicotinic system in the healthy aging brain and examine its role in memory and thinking processes in older and younger adults.
Read the detailed description
The cholinergic system has been shown to be the primary neurotransmitter system responsible for cognitive symptoms in dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and the nicotinic system specifically plays in cognition in healthy non-demented older adults (referred to as normal cognitive aging in this application). This is critical because the expansion of the healthy aging population will nonetheless show declines in cognition that fall short of dementia but still impact functional abilities and independence. Understanding the effects of age-related functional changes on the nicotinic system will elucidate one neurochemical mechanism underlying age-related changes in cognition and will provide information about how nicotinic dysfunction affects cognition in healthy older adults. Prior research has shown that the nicotinic system has a roll in attention and memory in healthy adults. More recently, with the increased use of brain functional magnetic resonance imaging (fMRI) in combination with psychopharmacological manipulations, data patterns have emerged that further define the role of the nicotinic system in cognition, aging, and dementia.
The investigators propose that nicotinic system changes are responsible for age differences in working memory task performance and brain activation. The investigators can observe the functioning of the nicotinic system by examining brain activation patterns in response to nicotinic blockade and stimulation. Increased dorsolateral prefrontal cortex (DLPFC) activation has been shown for older adults compared to younger adults and is hypothesized to be a compensation response for the aging process. The investigators propose that temporary antagonism of the nicotinic system will also produce increased DLPFC activation. However, the relationship between this increased activation and performance will be in different directions for older and younger adults. In older adults, the increased activation will be positively correlated with performance because it is a compensatory response. In younger adults, the increased activation will be negatively correlated with performance because it is a non-adaptive response to the temporary nicotinic antagonism. Nicotinic stimulation in older adults will reveal decreased DLPFC activation that will be negatively correlated with performance and this represents the "younger" pattern of the performance and activation relationship. The younger adults will have a similar pattern of activation and performance as the older adults after nicotinic stimulation because they are already performing optimally and will not receive any further enhancement. These data will further the understanding of a neurochemical mechanism involved in normal aging and how brain activation patterns relate to receptor function.
- Conditions
- Healthy Aging
- Being tested
- Nicotine patch, oral mecamylamine, placebo
- Keywords
- nicotinic system, cognitive aging, working memory, fMRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine patch, oral mecamylamine, placeboDrug
Each participant randomly receives one active drug or placebo on each of three study days.
| Study group | Role | What they receive |
|---|---|---|
| Older Adults | Experimental | Healthy adults aged 65-75 will participate in three study days where they are randomly assigned to receive either nicotine patch, oral mecamylamine, placebo and perform a working memory task during the fMRI. BOLD signal is the outcome measure. Receives: Drug: Nicotine patch, oral mecamylamine, placebo |
| Younger Adults | Experimental | Healthy adults aged 18-30 will participate in three study days where they are randomly assigned to receive either nicotine patch, oral mecamylamine, or placebo and perform a working memory task during the fMRI.BOLD signal is the outcome measure. Receives: Drug: Nicotine patch, oral mecamylamine, placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Age effects of nicotinic blockade
Examine the effects of nicotinic blockade compared to placebo on the relationship between working memory performance and brain activation using fMRI BOLD signal in older and younger adults.
Measured: After the completion of the third study day.
Age effects of nicotinic stimulation
Examine the effects of nicotinic stimulation compared to placebo on the relationship between working memory performance and brain activation using fMRI BOLD signal in older and younger adults.
Measured: After the completion of the third study day.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2018
- Study start1 Oct 2016
- Primary completion1 Dec 2021
- Study completion31 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy AgingStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Healthy older adults aged 65-75 and healthy younger adults aged 18-30 will be recruited. Each participant will take part in 3 nicotinic drug challenge days. The three drugs are counterbalanced across study days within each group and balanced by sex.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt University Medical Center
- Responsible party
- Principal investigator, Julie Dumas, University of Vermont
- Investigators
- Julie A Dumas, Ph.D., Principal investigator, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03408574
- Sponsor's protocol ID
- CHRMS 16-284
- Status last verified
- May 2023
- First submitted
- 3 Jan 2018
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Deidentified data will be available to be shared with other researchers. The Principal Investigator will make fMRI and behavioral data available as requested by researchers after the study is completed and data sets have been cleaned for quality and locked.
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Nicotinic Cholinergic System and Cognitive Aging
- ClinicalTrials.gov ID
- NCT03408574
- Acronym / sponsor ID
- CHRMS 16-284
- Conditions
- Healthy Aging
- Keywords
- nicotinic system, cognitive aging, working memory, fMRI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Collaborators
- Vanderbilt University Medical Center
- Study start
- 1 Oct 2016 (actual)
- Primary completion
- 1 Dec 2021 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 24 Jan 2018 (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.
Prior research has shown that a chemical system in the brain called the cholinergic system is primarily responsible for cognitive symptoms seen in people with dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and a subset of receptors called the nicotinic system plays in cognition in healthy non-demented older adults (referred to as normal cognitive aging). This is critical because the ever growing healthy aging population will show declines in cognition that fall short of dementia but still impact functional abilities and independence. Maintaining good nicotinic system functioning throughout adulthood may lessen the cognitive symptoms of aging. At this time, it is not clear what the biological cause of age-related changes in cognition is. This study will examine the role of the nicotinic system in the healthy aging brain and examine its role in memory and thinking processes in older and younger adults.
Detailed description
The cholinergic system has been shown to be the primary neurotransmitter system responsible for cognitive symptoms in dementia. While therapeutic benefits are clear in dementia, what remains uncertain is the role that the cholinergic system in general and the nicotinic system specifically plays in cognition in healthy non-demented older adults (referred to as normal cognitive aging in this application). This is critical because the expansion of the healthy aging population will nonetheless show declines in cognition that fall short of dementia but still impact functional abilities and independence. Understanding the effects of age-related functional changes on the nicotinic system will elucidate one neurochemical mechanism underlying age-related changes in cognition and will provide information about how nicotinic dysfunction affects cognition in healthy older adults. Prior research has shown that the nicotinic system has a roll in attention and memory in healthy adults. More recently, with the increased use of brain functional magnetic resonance imaging (fMRI) in combination with psychopharmacological manipulations, data patterns have emerged that further define the role of the nicotinic system in cognition, aging, and dementia.
The investigators propose that nicotinic system changes are responsible for age differences in working memory task performance and brain activation. The investigators can observe the functioning of the nicotinic system by examining brain activation patterns in response to nicotinic blockade and stimulation. Increased dorsolateral prefrontal cortex (DLPFC) activation has been shown for older adults compared to younger adults and is hypothesized to be a compensation response for the aging process. The investigators propose that temporary antagonism of the nicotinic system will also produce increased DLPFC activation. However, the relationship between this increased activation and performance will be in different directions for older and younger adults. In older adults, the increased activation will be positively correlated with performance because it is a compensatory response. In younger adults, the increased activation will be negatively correlated with performance because it is a non-adaptive response to the temporary nicotinic antagonism. Nicotinic stimulation in older adults will reveal decreased DLPFC activation that will be negatively correlated with performance and this represents the "younger" pattern of the performance and activation relationship. The younger adults will have a similar pattern of activation and performance as the older adults after nicotinic stimulation because they are already performing optimally and will not receive any further enhancement. These data will further the understanding of a neurochemical mechanism involved in normal aging and how brain activation patterns relate to receptor function.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Healthy older adults aged 65-75 and healthy younger adults aged 18-30 will be recruited. Each participant will take part in 3 nicotinic drug challenge days. The three drugs are counterbalanced across study days within each group and balanced by sex.
| Arm | Type | Receives |
|---|---|---|
| Older Adults | Experimental | Drug: Nicotine patch, oral mecamylamine, placeboHealthy adults aged 65-75 will participate in three study days where they are randomly assigned to receive either nicotine patch, oral mecamylamine, placebo and perform a working memory task during the fMRI. BOLD signal is the outcome measure. |
| Younger Adults | Experimental | Drug: Nicotine patch, oral mecamylamine, placeboHealthy adults aged 18-30 will participate in three study days where they are randomly assigned to receive either nicotine patch, oral mecamylamine, or placebo and perform a working memory task during the fMRI.BOLD signal is the outcome measure. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Normal cognition, not demented, no mild cognitive impairment. IQ greater than 80.
Key exclusion criteria (3 listed)
- Current use of barbiturates, rifampin, insulin, carbamezepine, oral hypoglycemics, antidepressants, diabetes, or untreated thyroid disease.
- In addition, the following exclusions are specific for the challenge drugs: heavy alcohol or coffee use, significant cardiovascular disease, ischemic heart disease, asthma, chronic obstructive pulmonary disease, active peptic ulcer, hyperthyroidism, pyloric stenosis, narrow angle glaucoma, epilepsy, or current Axis I psychiatric disorders.
- Current use of centrally active drugs and drugs with cholinergic properties. A minimum of 14 days will elapse between discontinuing centrally active or psychoactive agents and this study.
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 |
|---|---|---|
| Nicotine patch, oral mecamylamine, placeboEach participant randomly receives one active drug or placebo on each of three study days. | Drug | Older Adults, Younger Adults |
Primary outcome
Age effects of nicotinic blockade
Time frame: After the completion of the third study day.
Examine the effects of nicotinic blockade compared to placebo on the relationship between working memory performance and brain activation using fMRI BOLD signal in older and younger adults.
Age effects of nicotinic stimulation
Time frame: After the completion of the third study day.
Examine the effects of nicotinic stimulation compared to placebo on the relationship between working memory performance and brain activation using fMRI BOLD signal in older and younger adults.
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 9 May 2023.
- Individual participant dataSharing planned: Undecided. Deidentified data will be available to be shared with other researchers. The Principal Investigator will make fMRI and behavioral data available as requested by researchers after the study is completed and data sets have been cleaned for quality and locked.
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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.
Julie A Dumas, Ph.D. principal investigator
University of Vermont
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Healthy Aging, run by University of Vermont 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 1 inclusion and 3 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 9 May 2023. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Age effects of nicotinic blockade (time frame: After the completion of the third study day.). The study lists 2 primary outcomes in all. 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 9 May 2023.