Ignite Creation Date:
2024-05-06 @ 3:46 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04756232
Status:
RECRUITING
Last Update Posted:
2023-12-28
First Post:
2021-02-11
Brief Title:
Cholinergic Mechanisms of Attention in Aging
Sponsor:
Vanderbilt University Medical Center
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
Cholinergic Mechanisms of Attention in Aging
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will use an anticholinergic pharmacological probe to examine attention network function in SCD using EEG The overall hypothesis is that in older adults with SCD normal cognitive performance is maintained by compensatory attention network activity supported by enhanced cholinergic function The investigators anticipate that SCD will be associated with greater compensatory attention network activity and that disrupting this compensatory process through anticholinergic challenge will result in a greater negative effect on attentional performance Attention Network Test ANT and attention network functioning EEG in older adults with SCD compared to those without SCD
Detailed Description:
Overview Cognitively normal older adults with and without subjective cognitive decline SCD n 20 SCD 10 Non-SCD 10 will complete two study visits that will be double blinded and randomized for anticholinergic challenge mecamylaminescopolamine or placebo Drug challenge visits will include cognitive testing and an electroencephalography EEG session
Aim 1 Feasibility of EEG during mecamylaminescopolamine challenge
The primary outcome measures for Aim 1 will be the rate of completion of study visits with drug challenge and of completion of EEG tasks during the study visits with drug challenge
Attention Network Test The attention network test ANT is designed to test selective attention and combines attentional cues with a flanker task Behavioral measures of the ANT will be 1 Alerting reaction time RT non-cue trials - cue trials 2 Orienting RT neutral cue trials - spatial cue trials 3 Executive RT incongruent trials - congruent trials
EEG Task-related Event Related Potentials Each participant will complete the ANT during EEG with primary event relation potential ERP measures 1 Alerting early sensory ERP P1 amplitude 2 Orienting early sensory ERP P1 amplitude 3 Executive target and conflict evaluation ERP P3 amplitude Other ERP signals related to attention and sensory processing will be examined in exploratory analyses
Incidental Memory Incidental Memory Task during EEG a passive visual memory paradigm that will allow an exploratory examination of the relationship between SCD and brain activity for memory recognition
Psychomotor Speed The Choice Reaction Time task will be used as a test of psychomotor speed This task decomposes overall reaction time into recognition and motor components allowing for the assessment of response and motor time that cannot be attained during the ANT
Episodic Memory The Selective Reminding Task SRT is a multi-trial verbal list-learning task that offers measures of storage into and retrieval from both short term and long term memory and intrusion errors Outcome measures will be total recall 8 trials total recall failures 8 trials and delayed recall 20 minutes
Study Drug Administration During challenge drug study visits participants will receive double-blinded administration of study drug either 20 mg oral mecamylamine or 25 μgkg intravenous scopolamine or placebo The order of administration will be randomized across study days Randomization and dispensing will be managed by VUMC Investigational Drug Services
Mecamylamine is a centrally and peripherally active non-competitive antagonist of nicotine and presumably acetylcholine at C6 ganglionic type nicotinic receptors Peak cognitive and physiologic effects occur by 2-3 hours and dissipate by 4-6 hours after oral administration Scopolamine is a centrally active antimuscarinic anticholinergic compound and is a competitive antagonist of the effects of acetylcholine on postganglionic cholinergic nerves At the doses to be used in this study the expected physiologic effects of scopolamine include cycloplegia mydriasis drowsiness partial amnesia decreased bowel motility tachycardia and decreased salivation After intravenous administration the early effects of scopolamine include tachycardia dryness of mouth and inhibition of lacrimation and sweating Memory and attention changes are maximal between 90 and l50 minutes after an IV dose The drug is distributed throughout the body with a serum half-life of approximately 2-3 hours We have used both mecamylamine and scopolamine extensively in clinical studies in identical doses to those proposed here
Statistical Analysis PlanThis project is a pilot study to determine the feasibility and participant tolerability for conducting EEG during the mecamylaminescopolamine challenge The proposed sample size n 20 is designed to provide sufficient experience with the protocol to determine our ability to complete this protocol in a larger study and determine completion rates for the two participant groups SCD and Non-SCD as preliminary data for an NIH K01 application resubmission for Dr Albert Dr Hakmook Kang is the biostatistics consultant for this project
Descriptive statistics will be used to identify the rate of completion of study visits with drug challenge proportion of participants that complete both study days and of completion of EEG tasks proportion of participants who complete both tasks on each study visits with drug challenge These measures will be calculated for all participants n 20 and for participant groups separately SCD n 10 Non-SCD n 10
The investigators have hypothesized that 80 of participants will complete both study visits with drug challenge based on their experience using anticholinergic challenge with 88 of participants completing 2 study visits including anticholinergic challengeor placebo administration The investigators have hypothesized that 70 of participants will complete both EEG tasks ANT and incidental memory during study visits with drug challenge based on previous completion rates of 72 for non-EEG tasks during study visits including anticholinergic challenge or placebo administration and 100 for EEG tasks with no drug challenge
Aim 1 Feasibility of EEG during mecamylaminescopolamine challenge
The primary outcome measures for Aim 1 will be the rate of completion of study visits with drug challenge and of completion of EEG tasks during the study visits with drug challenge
Attention Network Test The attention network test ANT is designed to test selective attention and combines attentional cues with a flanker task Behavioral measures of the ANT will be 1 Alerting reaction time RT non-cue trials - cue trials 2 Orienting RT neutral cue trials - spatial cue trials 3 Executive RT incongruent trials - congruent trials
EEG Task-related Event Related Potentials Each participant will complete the ANT during EEG with primary event relation potential ERP measures 1 Alerting early sensory ERP P1 amplitude 2 Orienting early sensory ERP P1 amplitude 3 Executive target and conflict evaluation ERP P3 amplitude Other ERP signals related to attention and sensory processing will be examined in exploratory analyses
Incidental Memory Incidental Memory Task during EEG a passive visual memory paradigm that will allow an exploratory examination of the relationship between SCD and brain activity for memory recognition
Psychomotor Speed The Choice Reaction Time task will be used as a test of psychomotor speed This task decomposes overall reaction time into recognition and motor components allowing for the assessment of response and motor time that cannot be attained during the ANT
Episodic Memory The Selective Reminding Task SRT is a multi-trial verbal list-learning task that offers measures of storage into and retrieval from both short term and long term memory and intrusion errors Outcome measures will be total recall 8 trials total recall failures 8 trials and delayed recall 20 minutes
Study Drug Administration During challenge drug study visits participants will receive double-blinded administration of study drug either 20 mg oral mecamylamine or 25 μgkg intravenous scopolamine or placebo The order of administration will be randomized across study days Randomization and dispensing will be managed by VUMC Investigational Drug Services
Mecamylamine is a centrally and peripherally active non-competitive antagonist of nicotine and presumably acetylcholine at C6 ganglionic type nicotinic receptors Peak cognitive and physiologic effects occur by 2-3 hours and dissipate by 4-6 hours after oral administration Scopolamine is a centrally active antimuscarinic anticholinergic compound and is a competitive antagonist of the effects of acetylcholine on postganglionic cholinergic nerves At the doses to be used in this study the expected physiologic effects of scopolamine include cycloplegia mydriasis drowsiness partial amnesia decreased bowel motility tachycardia and decreased salivation After intravenous administration the early effects of scopolamine include tachycardia dryness of mouth and inhibition of lacrimation and sweating Memory and attention changes are maximal between 90 and l50 minutes after an IV dose The drug is distributed throughout the body with a serum half-life of approximately 2-3 hours We have used both mecamylamine and scopolamine extensively in clinical studies in identical doses to those proposed here
Statistical Analysis PlanThis project is a pilot study to determine the feasibility and participant tolerability for conducting EEG during the mecamylaminescopolamine challenge The proposed sample size n 20 is designed to provide sufficient experience with the protocol to determine our ability to complete this protocol in a larger study and determine completion rates for the two participant groups SCD and Non-SCD as preliminary data for an NIH K01 application resubmission for Dr Albert Dr Hakmook Kang is the biostatistics consultant for this project
Descriptive statistics will be used to identify the rate of completion of study visits with drug challenge proportion of participants that complete both study days and of completion of EEG tasks proportion of participants who complete both tasks on each study visits with drug challenge These measures will be calculated for all participants n 20 and for participant groups separately SCD n 10 Non-SCD n 10
The investigators have hypothesized that 80 of participants will complete both study visits with drug challenge based on their experience using anticholinergic challenge with 88 of participants completing 2 study visits including anticholinergic challengeor placebo administration The investigators have hypothesized that 70 of participants will complete both EEG tasks ANT and incidental memory during study visits with drug challenge based on previous completion rates of 72 for non-EEG tasks during study visits including anticholinergic challenge or placebo administration and 100 for EEG tasks with no drug challenge
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None