Cognitive ChangePhase 1NCT03281694
The Use of AVL-3288 to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine
A Phase 1 study testing Nicotine, AVL-3288 and Nicotine + AVL-3288 in people with Cognitive Change, run by University of Maryland, Baltimore.
Trial 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 mg/24 hrs) in healthy non-smokers, while monitoring the safety and tolerability of AVL-3288. Read more about this study
- Who is it for?
- Ages 21 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Change
- What is being tested?
- Nicotine, AVL-3288 and Nicotine + AVL-3288
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2018to Feb 2019
- 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 21 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 21-50 years.
- Male or female willing to use qualified methods of contraception for the study duration and up to 2 months after its end. Qualified methods are: intrauterine device, condoms, oral contraceptives, surgical sterilization of the subject or the partner at least one year in advance, or postmenopausal status of the female defined as at least two years without menstruation.
- No exposure to any nicotine-containing product in the last year.
- Smoked no more that 40 cigarettes, cigars or cigarillos in lifetime.
- Normal or corrected to normal vision (at least 20/80).
- Body weight 110-220 lbs.
Who cannot join
- Pregnant or breast-feeding.
- DSM Axis I mood, anxiety or psychotic disorder.
- Drug or alcohol abuse or dependence currently or in the last 2 years.
- Cardiovascular or cerebrovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities (see below).
- Uncontrolled hypertension (resting systolic BP >150 or diastolic >95 mm Hg).
- Hypotension (resting systolic BP below 90 or diastolic below 60).
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- Significant kidney or liver impairment.
- Moderate to severe asthma.
- Type I diabetes.
- Gastrointestinal illness.
- Use of any prescription or over-the-counter medication except birth control or non-steroidal antiinflammatory drugs on an as-needed basis.
- History of or current neurological illnesses, such as stroke, seizure disorders, neurodegenerative diseases, or organic brain syndrome.
- Learning disability, mental retardation, or any other condition that impedes cognition.
- Any surgeries requiring full anesthesia scheduled within 2 weeks of any of the study test sessions.
- Inability to perform the Rapid Visual Information Processing Task.
About this study
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 mg/24 hrs) in healthy non-smokers, while monitoring the safety and tolerability of AVL-3288.
Read the 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 Alzheimer's 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 mg/24 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.
- Conditions
- Cognitive Change
- Being tested
- Placebo, Nicotine, AVL-3288, Nicotine + AVL-3288
- Keywords
- nicotine, positive allosteric modulator, attention, cognition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
placebo skin patch and placebo oral solution
NicotineDrug
nicotine skin patch (7 mg/24 hrs) and placebo oral solution
AVL-3288Drug
placebo skin patch and AVL-3288 oral solution (3 mg)
Nicotine + AVL-3288Drug
nicotine skin patch (7 mg/24 hrs) and AVL-3288 oral solution (3 mg)
| Study group | Role | What they receive |
|---|---|---|
| Nicotine - AVL-3288 Interaction Study | Other | Over four different test days, all participants will be tested with Placebo, Nicotine, AVL-3288, and Nicotine + AVL-3288, in a counterbalanced sequence. Receives: Drug: Placebo; Drug: Nicotine; Drug: AVL-3288; Drug: Nicotine + AVL-3288 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Spatial Attentional Resource Allocation Task reaction time
average reaction time of trials with a signal detection response
Measured: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
Spatial Attentional Resource Allocation Task omission errors
percentage of trials on which no response was registered
Measured: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
Rapid Visual Information Processing Task signal detection
signal detection index based on hit rate and false alarm rate
Measured: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
Rapid Visual Information Processing Task reaction time
average reaction time on trials with a correct response
Measured: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
Change Detection Task accuracy
% of correct responses
Measured: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
Change Detection reaction time
average reaction time across trials
Measured: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
Secondary outcomes (3)
Vital signs: blood pressure
mm Hg
Measured: hourly for 8 hours on each test day
Vital signs: heart rate
beats per minute
Measured: hourly for 8 hours on each test day
ECG
QTc interval
Measured: Before and 4 hours after ingestion of oral solution on each test day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2017
- Study startMay 2018 (estimated)
- Primary completionFeb 2019 (estimated)
- Study completionFeb 2019 (estimated)
Why it stopped: Drug supplier did not come through.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive ChangeStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Buchanan, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03281694
- Sponsor's protocol ID
- HP-0009999
- Status last verified
- Nov 2024
- First submitted
- 6 Sep 2017
- Last updated
- 6 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study data will be made available, in de-identified form, to Anvyl LLC (Irvine, CA).
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of AVL-3288 to Potentiate the Attention-Enhancing Effects of Low-Dose Nicotine
- ClinicalTrials.gov ID
- NCT03281694
- Acronym / sponsor ID
- HP-0009999
- Conditions
- Cognitive Change
- Keywords
- nicotine, positive allosteric modulator, attention, cognition
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Drug supplier did not come through.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- May 2018 (estimated)
- Primary completion
- Feb 2019 (estimated)
- Study completion
- Feb 2019 (estimated)
- First posted
- 13 Sep 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.
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 mg/24 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 Alzheimer's 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 mg/24 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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nicotine - AVL-3288 Interaction Study | Other | Drug: Placebo, Drug: Nicotine, Drug: AVL-3288, Drug: Nicotine + AVL-3288Over four different test days, all participants will be tested with Placebo, Nicotine, AVL-3288, and Nicotine + AVL-3288, in a counterbalanced sequence. |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Aged 21-50 years.
- Male or female willing to use qualified methods of contraception for the study duration and up to 2 months after its end. Qualified methods are: intrauterine device, condoms, oral contraceptives, surgical sterilization of the subject or the partner at least one year in advance, or postmenopausal status of the female defined as at least two years without menstruation.
- No exposure to any nicotine-containing product in the last year.
- Smoked no more that 40 cigarettes, cigars or cigarillos in lifetime.
- Normal or corrected to normal vision (at least 20/80).
Key exclusion criteria (15 listed)
- Pregnant or breast-feeding.
- DSM Axis I mood, anxiety or psychotic disorder.
- Drug or alcohol abuse or dependence currently or in the last 2 years.
- Cardiovascular or cerebrovascular disease, such as history of myocardial infarction and ischemia, heart failure, angina, stroke, severe arrhythmias, or EKG abnormalities (see below).
- Uncontrolled hypertension (resting systolic BP >150 or diastolic >95 mm Hg).
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 |
|---|---|---|
| Placeboplacebo skin patch and placebo oral solution | Drug | Nicotine - AVL-3288 Interaction Study |
| Nicotinenicotine skin patch (7 mg/24 hrs) and placebo oral solution | Drug | Nicotine - AVL-3288 Interaction Study |
| AVL-3288placebo skin patch and AVL-3288 oral solution (3 mg) | Drug | Nicotine - AVL-3288 Interaction Study |
| Nicotine + AVL-3288nicotine skin patch (7 mg/24 hrs) and AVL-3288 oral solution (3 mg) | Drug | Nicotine - AVL-3288 Interaction Study |
Primary outcome
Spatial Attentional Resource Allocation Task reaction time
Time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
average reaction time of trials with a signal detection response
Spatial Attentional Resource Allocation Task omission errors
Time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
percentage of trials on which no response was registered
Rapid Visual Information Processing Task signal detection
Time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
signal detection index based on hit rate and false alarm rate
Rapid Visual Information Processing Task reaction time
Time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
average reaction time on trials with a correct response
Change Detection Task accuracy
Time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
% of correct responses
Change Detection reaction time
Time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day
average reaction time across trials
3 secondary outcomes
Vital signs: blood pressure
Time frame: hourly for 8 hours on each test day
Vital signs: heart rate
Time frame: hourly for 8 hours on each test day
ECG
Time frame: Before and 4 hours after ingestion of oral solution on each test day
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2024.
- Individual participant dataSharing planned: Yes. Study data will be made available, in de-identified form, to Anvyl LLC (Irvine, CA).
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nicotine, AVL-3288 and Nicotine + AVL-3288 in people with Cognitive Change, run by University of Maryland, Baltimore.
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 6 inclusion and 15 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: withdrawn, as of the sponsor's last update on 6 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Spatial Attentional Resource Allocation Task reaction time (time frame: 5 hrs after patch application (=1 hr after ingestion of oral solution) on each test day). The study lists 6 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 6 Nov 2024.