Focus: Effects of Nicotine and Alcohol on Brain CircuitsQfMRINCT02049268
Neural Mechanisms Underlying Nicotine and Alcohol Combinations
A study testing Nicotine + Alcohol in people with Focus: Effects of Nicotine and Alcohol on Brain Circuits, run by Mclean Hospital at 1 site in United States.
Trial summary
Nicotine and alcohol are frequently used together and their combined use contributes to more than half a million deaths each year, with more alcoholics dying from smoking-related diseases than from alcohol-related diseases. Read more about this study
- Who is it for?
- Ages 21 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Focus: Effects of Nicotine and Alcohol on Brain Circuits
- What is being tested?
- Nicotine + Alcohol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Dec 2015
- Phase
- Interventional
- 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 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male
- 21 to 40 years old
- Physically healthy (normal physical exam, ECG, blood and urine chemistries)
- Light/moderate cigarette smokers (greater than 10-20 cigarettes per week)
- Alcohol drinkers (10 or greater drinks per week)
- Must not be seeking treatment for their alcohol or tobacco use
Who cannot join
- Female
- Diagnosis of past or current alcohol dependence as assessed by Diagnostic and Statistic Manual, DSM-IV, criteria for alcohol dependence
- Diagnosis of cocaine, sedative, or opiate dependence using DSM-IV criteria
- Current diagnosis of Axis I disorder using DSM-IV criteria, or any Axis I disorder within past 5 years (excluding alcohol abuse, marijuana dependence or abuse)
- Current daily use of antipsychotic, antidepressant, or other psychoactive prescription drug, as well as daily use of non-prescription drugs
- Life threatening or unstable medical illness, or one that can create marked change in mental state
Show all 9Show fewer
- Heavy caffeine use (greater than 400 mg on a regular, daily basis)
- History of seizure disorder
- Hepatitis B or C positive, or history of i.v. drug use
Trial locations and contacts
1 site in 1 country.
About this study
Nicotine and alcohol are frequently used together and their combined use contributes to more than half a million deaths each year, with more alcoholics dying from smoking-related diseases than from alcohol-related diseases. Using a new multi-modal MRI approach combined with data fusion, the investigators propose to study how nicotine modulates alcohol-induced changes in the function of brain circuits. The investigators hypotheses are:
- functional connectivity (FC) in the reward network, containing components of the mesolimbic dopamine system, will be altered by alcohol, and additional increases in FC will be observed if nicotine is also present (e.g., additive effects).
- co-administration of nicotine will counteract the effects of alcohol on FC in multiple brain networks, including visual, sensorimotor and motor brain circuits, that may be associated with the impairing effects of alcohol
Read the detailed description
Long-term Objectives: Our long-term objective is to bring together non-invasive quantitative functional magnetic resonance imaging (q-fMRI) with a newly developed cutting-edge analysis method to study changes in neuronal metabolism and cerebrovascular function that occurs during psychoactive drug use.
Specific Aims: Our first specific aim is to validate the components of the q-fMRI acquisition, which requires several different kinds of fMRI scans (or multimodal measurements). The second aim then applies the q-MRI method to study the functional brain networks that define brain activity when a person is simply resting and not engaged in any activity. These networks each consist of a unique set of regions that spontaneously fluctuate together in order to be "tuned" for future task performance. The effects of nicotine and alcohol and their interaction on these resting state networks are the focus of the application of our new q-fMRI strategy. q-fMRI measurements require several different scans, including making measurements of perfusion and oxygen metabolism, and an integrated analysis of all of these different results will be much more informative than separate analyses of each measurement. However, the analysis method, the linked independent component analysis (linked ICA) approach is very new and has never been applied to q-fMRI measurements or any other measurements of psychoactive drug effects. Thus, the third aim is to apply this novel analysis method to data acquired under different drug conditions to identify patterns of related activity in our multimodal fMRI data.
Research Design and Methods: A randomized within-subject study of 23 healthy subjects will be done as follows: fMRI scanning will begin four hours after pre-treatment with either nicotine or placebo patch (randomized). Alcohol will then be consumed by subjects while in the scanner and a second scanning session will be done of the combination of nicotine (placebo) + alcohol to assess changes in resting state functional connectivity due to alcohol and nicotine and their interactions.
Significance: Linked ICA with q-fMRI measurements is an innovative strategy for studying brain function that could have a significant impact in the ability of fMRI to give an integrated picture of the spectrum of effects that drugs of abuse may have on brain function, and is thus ideally suited to the goals of the CEBRA mechanism. By applying this technique to study alcohol and nicotine co-use, we also will contribute greatly to the understanding of this significant health problem.
- Being tested
- Nicotine + Alcohol, Placebo Nicotine + Alcohol, Nicotine + Placebo Alcohol
- Keywords
- alcohol, nicotine, addiction, functional MRI, functional connectivity, brain circuits
- Medical subject headings
- Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine + AlcoholDrug
Also called Nicoderm CQ Clear, Absolute Vodka
14 mg nicotine patch applied in combination with vodka and orange juice alcoholic beverage (to reach blood alcohol level (BAL) = 0.08 based on subject weight, which is approximately 2-3 drinks for 400 mL volume)
Placebo Nicotine + AlcoholDrug
Also called Nicoderm CQ Clear, Absolute Vodka
Placebo nicotine patch applied in combination with vodka and orange juice alcoholic beverage (to reach BAL = 0.08 based on subject weight, which is approximately 2-3 drinks for 400 mL volume)
Nicotine + Placebo AlcoholDrug
Also called Nicoderm CQ Clear, Absolute Vodka
14 mg nicotine patch applied in combination with 400 mL orange juice beverage with a trace of alcohol to create placebo alcohol mixture.
| Study group | Role | What they receive |
|---|---|---|
| Nicotine + Alcohol | Experimental | A nicotine patch will be applied to the subject. After a 3-4 hour uptake period, subjects will undergo a single MRI session. Baseline (nicotine only) measurements will be made, then participants will drink an alcoholic beverage. Post-alcohol measurements will be made after a 20 minute uptake period. Receives: Drug: Nicotine + Alcohol |
| Placebo Nicotine + Alcohol | Experimental | A placebo nicotine patch will be applied to the subject. After a 3-4 hour uptake period, subjects will undergo a single MRI session. Baseline (placebo nicotine) measurements will be made, then participants will drink an alcoholic beverage. Post-alcohol measurements will be made after a 20 minute uptake period. Receives: Drug: Placebo Nicotine + Alcohol |
| Nicotine + Placebo Alcohol | Experimental | A nicotine patch will be applied to the subject. After a 3-4 hour uptake period, subjects will undergo a single MRI session. Baseline (nicotine only) measurements will be made, then participants will drink a placebo alcoholic beverage. Post-alcohol measurements will be made after a 20 minute uptake period. Receives: Drug: Nicotine + Placebo Alcohol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional connectivity of reward-related brain circuit
In a single 1.5 hour MRI session, functional connectivity of the reward circuit will be assessed with either nicotine or placebo nicotine on board. Participants will then drink an alcoholic or placebo alcohol beverage (whilst still in the scanner) and will be rescanned after a 20 minute resting period (also still in the scanner). The primary outcome is the pre- minus the post-alcohol functional connectivity of the reward brain circuit.
Measured: 1.5 hours
Secondary outcomes (2)
Exploratory investigation of oxygen metabolism and perfusion underlying the functional connectivity effects
An exploratory data fusion approach will be applied to the MRI measurements to evaluate patterns of related cerebrovascular and neural function in all brain circuits that are associated with nicotine and alcohol effects.
Measured: 1.5 hours
Functional connectivity of visual, motor, and sensorimotor brain circuits
In a single 1.5 hour MRI session, functional connectivity of the reward circuit will be assessed with either nicotine or placebo nicotine on board. Participants will then drink an alcohol or placebo alcohol beverage (whilst still in the scanner) and will be rescanned after a 20 minute resting period (also still in the scanner). The primary outcome is the pre- minus the post-alcohol functional connectivity for each brain circuit.
Measured: 1.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study startJul 2013
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Focus: Effects of Nicotine and Alcohol on Brain CircuitsStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lisa Nickerson, PhD, Mclean Hospital
- Investigators
- Lisa D Nickerson, PhD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02049268
- Sponsor's protocol ID
- 2012P000217
- Acronym
- QfMRI
- Status last verified
- Feb 2017
- First submitted
- 28 Jan 2014
- Last updated
- 3 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data sharing will be considered on a case by case basis to ensure IRB compliance.
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Mechanisms Underlying Nicotine and Alcohol Combinations
- ClinicalTrials.gov ID
- NCT02049268
- Acronym / sponsor ID
- QfMRI / 2012P000217
- Keywords
- alcohol, nicotine, addiction, functional MRI, functional connectivity, brain circuits
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 30 Jan 2014 (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.
Nicotine and alcohol are frequently used together and their combined use contributes to more than half a million deaths each year, with more alcoholics dying from smoking-related diseases than from alcohol-related diseases. Using a new multi-modal MRI approach combined with data fusion, the investigators propose to study how nicotine modulates alcohol-induced changes in the function of brain circuits. The investigators hypotheses are:
- functional connectivity (FC) in the reward network, containing components of the mesolimbic dopamine system, will be altered by alcohol, and additional increases in FC will be observed if nicotine is also present (e.g., additive effects).
- co-administration of nicotine will counteract the effects of alcohol on FC in multiple brain networks, including visual, sensorimotor and motor brain circuits, that may be associated with the impairing effects of alcohol
Detailed description
Long-term Objectives: Our long-term objective is to bring together non-invasive quantitative functional magnetic resonance imaging (q-fMRI) with a newly developed cutting-edge analysis method to study changes in neuronal metabolism and cerebrovascular function that occurs during psychoactive drug use.
Specific Aims: Our first specific aim is to validate the components of the q-fMRI acquisition, which requires several different kinds of fMRI scans (or multimodal measurements). The second aim then applies the q-MRI method to study the functional brain networks that define brain activity when a person is simply resting and not engaged in any activity. These networks each consist of a unique set of regions that spontaneously fluctuate together in order to be "tuned" for future task performance. The effects of nicotine and alcohol and their interaction on these resting state networks are the focus of the application of our new q-fMRI strategy. q-fMRI measurements require several different scans, including making measurements of perfusion and oxygen metabolism, and an integrated analysis of all of these different results will be much more informative than separate analyses of each measurement. However, the analysis method, the linked independent component analysis (linked ICA) approach is very new and has never been applied to q-fMRI measurements or any other measurements of psychoactive drug effects. Thus, the third aim is to apply this novel analysis method to data acquired under different drug conditions to identify patterns of related activity in our multimodal fMRI data.
Research Design and Methods: A randomized within-subject study of 23 healthy subjects will be done as follows: fMRI scanning will begin four hours after pre-treatment with either nicotine or placebo patch (randomized). Alcohol will then be consumed by subjects while in the scanner and a second scanning session will be done of the combination of nicotine (placebo) + alcohol to assess changes in resting state functional connectivity due to alcohol and nicotine and their interactions.
Significance: Linked ICA with q-fMRI measurements is an innovative strategy for studying brain function that could have a significant impact in the ability of fMRI to give an integrated picture of the spectrum of effects that drugs of abuse may have on brain function, and is thus ideally suited to the goals of the CEBRA mechanism. By applying this technique to study alcohol and nicotine co-use, we also will contribute greatly to the understanding of this significant health problem.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nicotine + Alcohol | Experimental | Drug: Nicotine + AlcoholA nicotine patch will be applied to the subject. After a 3-4 hour uptake period, subjects will undergo a single MRI session. Baseline (nicotine only) measurements will be made, then participants will drink an alcoholic beverage. Post-alcohol measurements will be made after a 20 minute uptake period. |
| Placebo Nicotine + Alcohol | Experimental | Drug: Placebo Nicotine + AlcoholA placebo nicotine patch will be applied to the subject. After a 3-4 hour uptake period, subjects will undergo a single MRI session. Baseline (placebo nicotine) measurements will be made, then participants will drink an alcoholic beverage. Post-alcohol measurements will be made after a 20 minute uptake period. |
| Nicotine + Placebo Alcohol | Experimental | Drug: Nicotine + Placebo AlcoholA nicotine patch will be applied to the subject. After a 3-4 hour uptake period, subjects will undergo a single MRI session. Baseline (nicotine only) measurements will be made, then participants will drink a placebo alcoholic beverage. Post-alcohol measurements will be made after a 20 minute uptake period. |
Who may qualify
- Ages
- 21 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male
- 21 to 40 years old
- Physically healthy (normal physical exam, ECG, blood and urine chemistries)
- Light/moderate cigarette smokers (greater than 10-20 cigarettes per week)
- Alcohol drinkers (10 or greater drinks per week)
Key exclusion criteria (9 listed)
- Female
- Diagnosis of past or current alcohol dependence as assessed by Diagnostic and Statistic Manual, DSM-IV, criteria for alcohol dependence
- Diagnosis of cocaine, sedative, or opiate dependence using DSM-IV criteria
- Current diagnosis of Axis I disorder using DSM-IV criteria, or any Axis I disorder within past 5 years (excluding alcohol abuse, marijuana dependence or abuse)
- Current daily use of antipsychotic, antidepressant, or other psychoactive prescription drug, as well as daily use of non-prescription drugs
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 + AlcoholAlso: Nicoderm CQ Clear, Absolute Vodka14 mg nicotine patch applied in combination with vodka and orange juice alcoholic beverage (to reach blood alcohol level (BAL) = 0.08 based on subject weight, which is approximately 2-3 drinks for 400 mL volume) | Drug | Nicotine + Alcohol |
| Placebo Nicotine + AlcoholAlso: Nicoderm CQ Clear, Absolute VodkaPlacebo nicotine patch applied in combination with vodka and orange juice alcoholic beverage (to reach BAL = 0.08 based on subject weight, which is approximately 2-3 drinks for 400 mL volume) | Drug | Placebo Nicotine + Alcohol |
| Nicotine + Placebo AlcoholAlso: Nicoderm CQ Clear, Absolute Vodka14 mg nicotine patch applied in combination with 400 mL orange juice beverage with a trace of alcohol to create placebo alcohol mixture. | Drug | Nicotine + Placebo Alcohol |
Primary outcome
Functional connectivity of reward-related brain circuit
Time frame: 1.5 hours
In a single 1.5 hour MRI session, functional connectivity of the reward circuit will be assessed with either nicotine or placebo nicotine on board. Participants will then drink an alcoholic or placebo alcohol beverage (whilst still in the scanner) and will be rescanned after a 20 minute resting period (also still in the scanner). The primary outcome is the pre- minus the post-alcohol functional connectivity of the reward brain circuit.
2 secondary outcomes
Exploratory investigation of oxygen metabolism and perfusion underlying the functional connectivity effects
Time frame: 1.5 hours
Functional connectivity of visual, motor, and sensorimotor brain circuits
Time frame: 1.5 hours
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 3 Feb 2017.
- Individual participant dataSharing planned: No. Data sharing will be considered on a case by case basis to ensure IRB compliance.
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.
Lisa D Nickerson, PhD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nicotine + Alcohol in people with Focus: Effects of Nicotine and Alcohol on Brain Circuits, run by Mclean Hospital 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 6 inclusion and 9 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 3 Feb 2017. 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.
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?
Functional connectivity of reward-related brain circuit (time frame: 1.5 hours). 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 3 Feb 2017.