Non-smokerPhase 1NNSGNCT01819259
Nicotine, Non-Smokers With and Without ADHD, and Genetics Study
A Phase 1 study testing Nicotine nasal spray in people with Non-smoker and ADHD, run by Scott Kollins, PhD at 1 site in United States.
Trial summary
The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration. Study Hypotheses: 1. Read more about this study
- Who is it for?
- Ages 18 to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-smoker, ADHD
- What is being tested?
- Nicotine nasal spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to 30 Jun 2018
- 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 25 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18-25 years of age.
- male or female; if female of childbearing potential, must be using an acceptable form of contraception.
- ADHD Diagnosis:
- for ADHD Groups: confirmed diagnosis, any subtype as determined by the clinician administered CAADID and clinical interview.
- for Control Groups: NO diagnosis of ADHD as determined by clinician administered CAADID and clinical interview.
- ADHD Symptom Ratings:
Show all 11Show fewer
- for ADHD Groups: T-Score > 65 on one of the DSM-IV relevant scales (Inattentive Symptoms, Hyperactive-Impulsive Symptoms, Total Symptoms or ADHD Index) on both the Self-Report and Observer versions of the CAARS.
- for Control Groups: T-Score < 60 on all of the DSM-IV relevant scales (Inattentive Symptoms, Hyperactive-Impulsive Symptoms, Total Symptoms or ADHD Index) on both the Self-Report and Observer versions of the CAARS.
- never smoked an entire cigarette; no tobacco exposure in past 3 years.
- expired air CO level < 3 ppm; plasma nicotine levels < 5 ng/mL.
- cognitive functioning > 80 as assessed by the Kaufman Brief Intelligence test, Second Edition(KBIT-II).
Who cannot join
- history of chronic/significant medical condition.
- current or past 12 month use of prescription medications for ADHD group.
- meets criteria for any other Axis I Disorder (determined by the Structured Diagnostic Interview for DSM; SCID) other than nicotine dependence that is significantly impairing and would contraindicate participation in the present study.
- meets criteria for any Axis II Disorder.
- current substance abuse or dependence or history within the last 12 months; expired breath alcohol level > 0.0; Positive urine drug screen for any of the following: cannabis, amphetamines, opioids, benzodiazepines, barbiturates, cocaine.
- inability to understand written and/or spoken English language.
- reported uncertainty about being able to remain a nonsmoker in the coming year.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Child and Family Study Center
Durham, North Carolina, 27705
About this study
The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration.
Study Hypotheses:
- that nicotine will produce greater positive and fewer negative/aversive subjective effects in individuals with ADHD. The study team also hypothesizes that nicotine will improve performance to a greater degree in those with ADHD.
- that individuals in the ADHD group will exhibit an increase in choices for nicotine vs. placebo in both conditions (i.e., main effect) and that this effect will be more pronounced in the High Demand vs. Low Demand conditions (i.e. Group x Condition interaction). Also that greater performance enhancing effects of nicotine will be associated with greater nicotine choice during the high demand cognitive condition.
- that the main effects of ADHD status on nicotine reinforcement will be heightened in the presence of certain genotypes. Also that the main effects of ADHD status on nicotine reinforcement will be heightened in the presence of certain genotypes. Finally that exposure to nicotine will alter epigenetic patterns in DNA
Read the detailed description
Individuals with Attention Deficit Hyperactivity Disorder (ADHD) are more likely to smoke cigarettes than the general population, start smoking at a younger age, progress to regular use and dependence more quickly, and have a harder time quitting. The specific factors that confer risk for smoking-related outcomes among those with ADHD have not been thoroughly evaluated, though a range of possibilities exist. The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration. Target completion population of the study is 150 (75 ADHD, 75 CTRL), although the population potentially screened will be 200. The investigators will systematically assess the effects of two doses of intranasally administered nicotine versus placebo. In addition, nicotine self-administration will be evaluated under conditions that are likely to be more cognitively challenging among individuals with ADHD. If the subject passes screen and their status as never smoking up to 1 cigarette in their lifetime, they will be scheduled for a the first of five experimental sessions: 3 fixed dose sessions, followed by 2 choice sessions. Each of the 3 fixed dose sessions will be identical except for the dose of nicotine evaluated. During choice sessions, the nicotine reinforcement procedures will be implemented. Finally to assess the moderating effects of genotype on the reinforcing effects of nicotine in non-smokers analyses will focus primarily with hierarchical regression models that covary gender and population substructure to assess effects of genotype on nicotine sensitivity outcomes. Further epigenetics analysis will be conducted, related to the initial nicotine exposure at the Fixed Dose Sessions.
- Conditions
- Non-smoker, ADHD
- Being tested
- Nicotine nasal spray, Placebo
- Keywords
- Nonsmoker, ADHD, Nicotine, Nicotine Nasal Spray, Nicotine Reinforcement
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine nasal sprayDrug
This study will use nicotine nasal spray to safely and effectively model the effects of initial smoking experiences in nonsmokers. Neither the safety nor the effectiveness of this drug will be assessed. The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration. The effects of two doses of intranasally administered nicotine versus placebo will be assessed. In addition, nicotine self-administration will be evaluated under conditions that are likely to be more cognitively challenging among individuals with ADHD.
PlaceboDrug
Also called Sterile normal saline.
| Study group | Role | What they receive |
|---|---|---|
| ADHD Nonsmokers | Active comparator | All participants will be non-smokers defined as never having smoked an entire cigarette and no tobacco use in the past 3 years. The group will then be split into those diagnosed with ADHD/ADD and controls for comparison. Receives: Drug: Nicotine nasal spray; Drug: Placebo |
| Non-ADHD Nonsmokers | Active comparator | All participants will be non-smokers defined as never having smoked an entire cigarette and no tobacco use in the past 3 years. The group will then be split into those diagnosed with ADHD/ADD and controls for comparison. Receives: Drug: Nicotine nasal spray; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cognitive performance.
The study team will use the Conners Continuous Performance Test (CPT) and n-Back Task to assess the effects of two doses of intranasally administered nicotine versus placebo on cognitive performance. Planned timeframe for measuring outcome (total 2 months). 1 month: Screen, 3 Experimental Sessions and 2 Sampling Sessions. 2nd month: Phone Follow-up
Measured: 2 months
Differences in Subjective Effects.
The study team will use 3 questionnaires to assess the subjective effects of two dose levels of intranasally administered nicotine versus placebo. The DEQ (Drug Effects Questionnaire) will assess a range of reward, sensory, and mood effects. The Positive Affect and Negative Affect Scale (PANAS) and The Profile of Mood States (POMS) will also be used to assess mood and affect. Length of time between each of the 5 sessions may vary from 1 day up to several weeks. All 5 sessions are expected to be complete in approximately 90 days.
Measured: Session 1 (within 30 days of screening), Session 2, Session 3, Session 4, Session 5 (approximately 3 months).
Change in Physiological Effects.
Throughout the study, vitals and urinary cotinine levels will be assessed. This will first be conducted to develop baseline participate data for the overall study, and also each particular session. Heart rate and blood pressure will be collected multiple times during each session to see any changes in physiological response to two dose levels of intranasally administered nicotine versus placebo. Urinary cotinine will then continue to be assessed, at the beginning of each session to assess levels post nicotine exposure as subjects progress through study. Length of time between each of the 5 sessions may vary from 1 day up to several weeks. All 5 sessions are expected to be complete in approximately 90 days.
Measured: Session 1 (within 30 days of screening), Session 2, Session 3, Session 4, Session 5; (approximately 3 months).
Change in Effects of Nicotine Reinforcement.
In both Choice Sampling Sessions, subjects are exposed to both the full (i.e. 2 sprays of nicotine nasal spray) and placebo (i.e. 2 sprays of placebo spray) levels of nicotine exposure. In 1 of 2 of sessions, they then perform a High Cognitive Demand task (i.e. the PERMP or 10 minute math test). Potential monetary reward, based on performance (i.e. number problems correct), is noted to subject. Post the exposure trials of the session, the subject can then choose (blinded) 1 of 3 dose levels, via self-administering 2 sprays of either or both bottles. This Choice Sampling trial part the session occurs 5 times, and then an actual monetary performance reward is given.
Measured: Study visits 4 and 5, both within 90 days of screening.
Genetics Effects on Nicotine Reinforcement.
Agenetic analyses will be conducted, from serum samples collected from subjects. This will assess specific polymorphisms of DAT1, DRD2, DRD4, 5HTTLPR, and MAO genes to determine if they are linked to moderating the association between ADHD diagnostic status and subjective/mood, performance, and reinforcing effects of nicotine.
Measured: Screening
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2013 (estimated)
- Study startJan 2013
- Primary completion30 Jun 2018
- Study completion30 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-smokerStudies 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
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scott Kollins, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor-investigator, Scott Kollins, PhD, Duke University
- Investigators
- Scott H Kollins, Ph.D., Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01819259
- Sponsor's protocol ID
- Pro00037792
- Other IDs
- 1R01DA033080
- Acronym
- NNSG
- Status last verified
- Nov 2018
- First submitted
- 18 Mar 2013
- Last updated
- 30 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nicotine, Non-Smokers With and Without ADHD, and Genetics Study
- ClinicalTrials.gov ID
- NCT01819259
- Acronym / sponsor ID
- NNSG / Pro00037792
- Conditions
- Non-smoker, ADHD
- Keywords
- Nonsmoker, ADHD, Nicotine, Nicotine Nasal Spray, Nicotine Reinforcement
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 136 participants (actual)
- Lead sponsor
- Scott Kollins, PhDUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Jan 2013 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 30 Jun 2018 (actual)
- First posted
- 27 Mar 2013 (estimated)
- 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.
The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration.
Study Hypotheses:
- that nicotine will produce greater positive and fewer negative/aversive subjective effects in individuals with ADHD. The study team also hypothesizes that nicotine will improve performance to a greater degree in those with ADHD.
- that individuals in the ADHD group will exhibit an increase in choices for nicotine vs. placebo in both conditions (i.e., main effect) and that this effect will be more pronounced in the High Demand vs. Low Demand conditions (i.e. Group x Condition interaction). Also that greater performance enhancing effects of nicotine will be associated with greater nicotine choice during the high demand cognitive condition.
- that the main effects of ADHD status on nicotine reinforcement will be heightened in the presence of certain genotypes. Also that the main effects of ADHD status on nicotine reinforcement will be heightened in the presence of certain genotypes. Finally that exposure to nicotine will alter epigenetic patterns in DNA
Detailed description
Individuals with Attention Deficit Hyperactivity Disorder (ADHD) are more likely to smoke cigarettes than the general population, start smoking at a younger age, progress to regular use and dependence more quickly, and have a harder time quitting. The specific factors that confer risk for smoking-related outcomes among those with ADHD have not been thoroughly evaluated, though a range of possibilities exist. The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration. Target completion population of the study is 150 (75 ADHD, 75 CTRL), although the population potentially screened will be 200. The investigators will systematically assess the effects of two doses of intranasally administered nicotine versus placebo. In addition, nicotine self-administration will be evaluated under conditions that are likely to be more cognitively challenging among individuals with ADHD. If the subject passes screen and their status as never smoking up to 1 cigarette in their lifetime, they will be scheduled for a the first of five experimental sessions: 3 fixed dose sessions, followed by 2 choice sessions. Each of the 3 fixed dose sessions will be identical except for the dose of nicotine evaluated. During choice sessions, the nicotine reinforcement procedures will be implemented. Finally to assess the moderating effects of genotype on the reinforcing effects of nicotine in non-smokers analyses will focus primarily with hierarchical regression models that covary gender and population substructure to assess effects of genotype on nicotine sensitivity outcomes. Further epigenetics analysis will be conducted, related to the initial nicotine exposure at the Fixed Dose Sessions.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ADHD Nonsmokers | Active comparator | Drug: Nicotine nasal spray, Drug: PlaceboAll participants will be non-smokers defined as never having smoked an entire cigarette and no tobacco use in the past 3 years. The group will then be split into those diagnosed with ADHD/ADD and controls for comparison. |
| Non-ADHD Nonsmokers | Active comparator | Drug: Nicotine nasal spray, Drug: PlaceboAll participants will be non-smokers defined as never having smoked an entire cigarette and no tobacco use in the past 3 years. The group will then be split into those diagnosed with ADHD/ADD and controls for comparison. |
Who may qualify
- Ages
- 18 to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 18-25 years of age.
- male or female; if female of childbearing potential, must be using an acceptable form of contraception.
- ADHD Diagnosis:
- ADHD Symptom Ratings:
- never smoked an entire cigarette; no tobacco exposure in past 3 years.
Key exclusion criteria (7 listed)
- history of chronic/significant medical condition.
- current or past 12 month use of prescription medications for ADHD group.
- meets criteria for any other Axis I Disorder (determined by the Structured Diagnostic Interview for DSM; SCID) other than nicotine dependence that is significantly impairing and would contraindicate participation in the present study.
- meets criteria for any Axis II Disorder.
- current substance abuse or dependence or history within the last 12 months; expired breath alcohol level > 0.0; Positive urine drug screen for any of the following: cannabis, amphetamines, opioids, benzodiazepines, barbiturates, cocaine.
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 nasal sprayThis study will use nicotine nasal spray to safely and effectively model the effects of initial smoking experiences in nonsmokers. Neither the safety nor the effectiveness of this drug will be assessed. The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration. The effects of two doses of intranasally administered nicotine versus placebo will be assessed. In addition, nicotine self-administration will be evaluated under conditions that are likely to be more cognitively challenging among individuals with ADHD. | Drug | ADHD Nonsmokers, Non-ADHD Nonsmokers |
| PlaceboAlso: Sterile normal saline. | Drug | ADHD Nonsmokers, Non-ADHD Nonsmokers |
Primary outcome
Change in cognitive performance.
Time frame: 2 months
The study team will use the Conners Continuous Performance Test (CPT) and n-Back Task to assess the effects of two doses of intranasally administered nicotine versus placebo on cognitive performance. Planned timeframe for measuring outcome (total 2 months). 1 month: Screen, 3 Experimental Sessions and 2 Sampling Sessions. 2nd month: Phone Follow-up
Differences in Subjective Effects.
Time frame: Session 1 (within 30 days of screening), Session 2, Session 3, Session 4, Session 5 (approximately 3 months).
The study team will use 3 questionnaires to assess the subjective effects of two dose levels of intranasally administered nicotine versus placebo. The DEQ (Drug Effects Questionnaire) will assess a range of reward, sensory, and mood effects. The Positive Affect and Negative Affect Scale (PANAS) and The Profile of Mood States (POMS) will also be used to assess mood and affect. Length of time between each of the 5 sessions may vary from 1 day up to several weeks. All 5 sessions are expected to be complete in approximately 90 days.
Change in Physiological Effects.
Time frame: Session 1 (within 30 days of screening), Session 2, Session 3, Session 4, Session 5; (approximately 3 months).
Throughout the study, vitals and urinary cotinine levels will be assessed. This will first be conducted to develop baseline participate data for the overall study, and also each particular session. Heart rate and blood pressure will be collected multiple times during each session to see any changes in physiological response to two dose levels of intranasally administered nicotine versus placebo. Urinary cotinine will then continue to be assessed, at the beginning of each session to assess levels post nicotine exposure as subjects progress through study. Length of time between each of the 5 sessions may vary from 1 day up to several weeks. All 5 sessions are expected to be complete in approximately 90 days.
Change in Effects of Nicotine Reinforcement.
Time frame: Study visits 4 and 5, both within 90 days of screening.
In both Choice Sampling Sessions, subjects are exposed to both the full (i.e. 2 sprays of nicotine nasal spray) and placebo (i.e. 2 sprays of placebo spray) levels of nicotine exposure. In 1 of 2 of sessions, they then perform a High Cognitive Demand task (i.e. the PERMP or 10 minute math test). Potential monetary reward, based on performance (i.e. number problems correct), is noted to subject. Post the exposure trials of the session, the subject can then choose (blinded) 1 of 3 dose levels, via self-administering 2 sprays of either or both bottles. This Choice Sampling trial part the session occurs 5 times, and then an actual monetary performance reward is given.
Genetics Effects on Nicotine Reinforcement.
Time frame: Screening
Agenetic analyses will be conducted, from serum samples collected from subjects. This will assess specific polymorphisms of DAT1, DRD2, DRD4, 5HTTLPR, and MAO genes to determine if they are linked to moderating the association between ADHD diagnostic status and subjective/mood, performance, and reinforcing effects of nicotine.
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 30 Nov 2018.
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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.
Scott H Kollins, Ph.D. principal investigator
Duke Health
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 testing Nicotine nasal spray in people with Non-smoker and ADHD, run by Scott Kollins, PhD 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 11 inclusion and 7 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 30 Nov 2018. 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?
Change in cognitive performance. (time frame: 2 months). The study lists 5 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 30 Nov 2018.