Ignite Creation Date:
2024-05-06 @ 10:32 AM
Last Modification Date:
2024-10-26 @ 12:31 PM
Study NCT ID:
NCT03281694
Status:
WITHDRAWN
Last Update Posted:
2019-09-13
First Post:
2017-09-06
Brief Title:
The Use of AVL-3288 to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
The Use of AVL-3288 to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine
Status:
WITHDRAWN
Status Verified Date:
2017-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Drug supplier did not come through
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Single-center randomized double-blind placebo-controlled proof-of-principle study to evaluate potential cognitive benefits of a single oral dose of AVL-3288 3 mg in the presence and absence of transdermal nicotine 7 mg24 hrs in healthy non-smokers while monitoring the safety and tolerability of AVL-3288
Detailed Description:
Nicotinic acetylcholine receptor nAChR agonists such as nicotine have been shown to enhance cognitive performance especially functions in the attention domain Efforts have been made to develop similar compounds as therapeutic agents for disorders such as schizophrenia or Alzheimers disease Over the last two decades drug development has invested into novel nAChR agonists Effects have generally been in the expected direction but tended to be of small magnitude A potential way of increasing the effect size ceiling is by co-administering a nAChR positive allosteric modulator PAM PAMs generally do not activate the nAChR on their own but bind to a second modulatory site and facilitate agonist-induced responses The present study is aimed at testing the effects of AVL-3288 a PAM selective for the α7 nAChR subtype that is thought to be of particular relevance for cognition in schizophrenia on cognitive task performance and on nicotine-induced improvements in cognitive task performance in healthy adult non-smokers
The aim of the present study is to provide the proof-of-principle that the attention-enhancing effects of the prototypical nAChR agonist nicotine can be potentiated by an α7 nAChR PAM AVL-3288 Potentiation of nAChR agonist effects by PAMs have been shown in preclinical behavioral assays The availability of AVL-3288 as a safe pure nAChR PAM for human research allows testing the hypothesis that nicotine and AVL-3288 will have additive or synergistic effects such that the attention-enhancing effects of nicotine and AVL-3288 combined will be greater than the effects of either drug alone
AVL-3288 has shown preclinical efficacy in rat paradigms of attention and memory including models of cognitive dysfunction1-3 A human study in healthy adults reported no adverse effects associated with AVL-3288 tested at doses of 3 10 and 30 mg Some of the participants tested with 3 mg were smokers some on nicotine replacement
The present study will adopt a repeated measures design in which a single group of 24 healthy non-smokers will complete 4 test sessions in each of which they perform the same three cognitive paradigms In each session a skin patch will be administered 5 hrs prior to testing and a solution 3 mL will be administered by mouth 1 hr prior to testing The skin patch is either a 7 mg24 hrs nicotine patch or a placebo patch The solution either contains AVL-3288 3 mg or is inactive diluent only Over the 4 test sessions each participant will be tested with Placebo Placebo Nicotine Placebo Placebo AVL-3288 and Nicotine AVL-3288 in a 2x2 factorial design The sequence of test conditions will be only known to the statistician and pharmacist and counterbalanced across subjects
The aim of the present study is to provide the proof-of-principle that the attention-enhancing effects of the prototypical nAChR agonist nicotine can be potentiated by an α7 nAChR PAM AVL-3288 Potentiation of nAChR agonist effects by PAMs have been shown in preclinical behavioral assays The availability of AVL-3288 as a safe pure nAChR PAM for human research allows testing the hypothesis that nicotine and AVL-3288 will have additive or synergistic effects such that the attention-enhancing effects of nicotine and AVL-3288 combined will be greater than the effects of either drug alone
AVL-3288 has shown preclinical efficacy in rat paradigms of attention and memory including models of cognitive dysfunction1-3 A human study in healthy adults reported no adverse effects associated with AVL-3288 tested at doses of 3 10 and 30 mg Some of the participants tested with 3 mg were smokers some on nicotine replacement
The present study will adopt a repeated measures design in which a single group of 24 healthy non-smokers will complete 4 test sessions in each of which they perform the same three cognitive paradigms In each session a skin patch will be administered 5 hrs prior to testing and a solution 3 mL will be administered by mouth 1 hr prior to testing The skin patch is either a 7 mg24 hrs nicotine patch or a placebo patch The solution either contains AVL-3288 3 mg or is inactive diluent only Over the 4 test sessions each participant will be tested with Placebo Placebo Nicotine Placebo Placebo AVL-3288 and Nicotine AVL-3288 in a 2x2 factorial design The sequence of test conditions will be only known to the statistician and pharmacist and counterbalanced across subjects
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