Alcohol Use DisorderNAUDNCT03338933

Neurobiology of Alcohol and Nicotine Co-Addiction

An observational study of Alcohol Use Disorder and Nicotine Use Disorder, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This proposal addresses the critical absence of information about the neurobiology of recovery from Alcohol Use Disorder (AUD) in alcohol and nicotine users. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Alcohol Use Disorder, Nicotine Use Disorder
What is being tested?: magnetic resonance imaging (MRI)
Type of treatment: Lifestyle or therapy programme
How many people: 109 participants
Where: 1 siteUnited States
Study dates: 8 Feb 2018to 3 Jan 2023
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 55 years
All sexes
Healthy volunteers accepted
Adult

Study population: Participants will be recruited from the Portland VA, Oregon Health \& Science University, community substance abuse treatment programs and by advertisement.

Who may be able to join

None

Who cannot join

None

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Portland Health Care System, Portland, OR
Portland, Oregon, 97207-2964

Other trials in United States

About this study

This proposal addresses the critical absence of information about the neurobiology of recovery from Alcohol Use Disorder (AUD) in alcohol and nicotine users.

Read the detailed description

This proposal addresses the critical absence of information about the neurobiology of recovery from Alcohol Use Disorder (AUD) in alcohol and nicotine users. AUD and nicotine use disorder (NUD) are the most commonly abused (non-prescription) substances in the U.S. Co-addiction is particularly high in military veterans. Although nationwide estimates peg the rate of AUD/NUD co-addiction at 80%, the Substance Abuse Treatment Program (SATP) at the Veterans Affairs Portland Health Care System (VAPORHCS) finds that 90% of veterans treated for AUD also meet criteria for NUD. The investigators hypothesize that a support vector machine learning algorithm will be able to use the measures to classify subjects as AUD, NUD both or neither and that the algorithm will predict outcome (sobriety or relapse) at three months.

Conditions: Alcohol Use Disorder, Nicotine Use Disorder
Being tested: magnetic resonance imaging (MRI)
Medical subject headings: Alcoholism, Tobacco Use Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

magnetic resonance imaging (MRI)Behavioural
All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.

Study groups in NCT03338933
Study group	Role	What they receive
Control Group		No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent. Receives: Behavioral: magnetic resonance imaging (MRI)
Nicotine Group		Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance Receives: Behavioral: magnetic resonance imaging (MRI)
Nicotine and Alcohol Group		DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling. Receives: Behavioral: magnetic resonance imaging (MRI)
Alcohol Group		DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling. Receives: Behavioral: magnetic resonance imaging (MRI)

What is being measured

The primary outcome is the main question the study is designed to answer.

Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
The DSN-back is a cognitive task used to assess working memory and attention. Participants view a sequence of letters presented on a screen, flanked by either drug-related or neutral images, and are instructed to identify matches occurring N steps earlier. Neural activation during high working memory demand condition (2-back) relative to the low working memory condition (0-back) was investigated. Inconsistent activation patterns across regions may indicate impaired neural processing in regions critical for cognitive control, emotion regulation, and reward processing, commonly reported in substance use disorders. Values closer to 0 (no change) in regions responsible for emotion regulation and cognitive control (e.g., Amygdala, ACC) may indicate reduced task-specific engagement where drug-related processes may be dominating neural activity.
Measured: Baseline
Brain Activation During Resting State MRI.
This outcome measures resting-state functional connectivity (rsFC) of the striatum using seed-based analysis of resting-state fMRI data. FC values, expressed as Fisher z-transformed correlation coefficients, quantify the strength of synchronization between the striatum seed region and other brain areas. Positive values indicate synchronized activity, while negative values reflect anticorrelation. Altered rsFC of the striatum, a hub for reward processing, habit formation, and executive control, is linked to alcohol and nicotine use disorders and may indicate impaired regulation of cravings and heightened sensitivity to substance-related cues. Investigating rsFC patterns may identify biomarkers of addiction severity, predict treatment outcomes, and inform potential therapeutic targets.
Measured: Baseline
Brain Cortical Thickness Assessed During MRI
This outcome measures cortical thickness (millimeters) across brain regions using structural MRI. Cortical thickness reflects the integrity of gray matter and is influenced by factors such as neurodegeneration, plasticity, and development. Reductions in cortical thickness, particularly in prefrontal and limbic regions, are associated with impaired cognitive control, emotion regulation, and decision-making in substance use disorders.
Measured: Baseline
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Fractional Anisotropy (FA) is a scalar metric derived from diffusion-weighted MRI that quantifies the degree of directional dependence (anisotropy) of water diffusion in brain white matter, with values ranging from 0 (isotropic diffusion) to 1 (maximally anisotropic diffusion). Increases in FA may reflect greater white matter organization and integrity, while decreases often indicate microstructural damage, demyelination, or axonal loss. FA measurements were averaged within predefined regions of interest (ROIs) to assess the integrity of white matter in various brain regions associated with cognitive, motor, and emotional processing. Decreased FA in tracts such as the corpus callosum or prefrontal pathways may reflect impaired communication between brain regions involved in reward processing and cognitive control in substance use disorders.
Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Feb 20183 Jan 2023

First posted9 Nov 2017
Study start8 Feb 2018
Primary completion3 Jan 2023
Study completion3 Jan 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe 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: Observational
Observational model: Case-control
Time perspective: Prospective
Enrolment: 109 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03338933
Sponsor's protocol ID: NURA-002-17S
Other IDs: 17321
Acronym: NAUD
Status last verified: Feb 2025
First submitted: 6 Nov 2017
Last updated: 13 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Alcohol Use Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neurobiology of Alcohol and Nicotine Co-Addiction
ClinicalTrials.gov ID: NCT03338933
Acronym / sponsor ID: NAUD / NURA-002-17S
Conditions: Alcohol Use Disorder, Nicotine Use Disorder
Study type: Observational
Recruitment status: Completed
Enrolment: 109 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Collaborators: Oregon Health and Science University
Study start: 8 Feb 2018 (actual)
Primary completion: 3 Jan 2023 (actual)
Study completion: 3 Jan 2023 (actual)
First posted: 9 Nov 2017 (actual)
Results: Posted 13 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This proposal addresses the critical absence of information about the neurobiology of recovery from Alcohol Use Disorder (AUD) in alcohol and nicotine users.

Detailed description

Study design

Observational model: Case-control
Time perspective: Prospective
Number of arms: 4

Arm	Type	Receives
Control Group	–	Behavioral: magnetic resonance imaging (MRI)No history of addiction to any substance or gambling. Less than 20 lifetime cigarettes or equivalent.
Nicotine Group	–	Behavioral: magnetic resonance imaging (MRI)Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) criteria for Nicotine Use Disorder. Current smoker, at least 10 cigarettes per day. No history of addiction to any other substance
Nicotine and Alcohol Group	–	Behavioral: magnetic resonance imaging (MRI)DSM-V criteria for Nicotine Use Disorder and Alcohol Use Disorder. At least 8 heavy drinking episodes in the past month. Current smoker. Alcohol free from 2 to 4 weeks. No history of addiction to other substances or gambling.
Alcohol Group	–	Behavioral: magnetic resonance imaging (MRI)DSM-V criteria for Alcohol use Disorder. At least 8 heavy drinking episodes in the past month. Abstinent for at least 2 weeks and no more than 4 weeks. Less than 20 lifetime cigarettes or equivalent. No history of addiction to any other substances or gambling.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult
Study population: Participants will be recruited from the Portland VA, Oregon Health \& Science University, community substance abuse treatment programs and by advertisement.

Key inclusion criteria (1 listed)

None

Key exclusion criteria (1 listed)

None

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
magnetic resonance imaging (MRI)All subjects will undergo a baseline MRI and subjects in both alcohol groups (alcohol use disorder and combined alcohol and nicotine use disorder) will undergo a followup MRI 3 months after baseline.	Behavioural	Alcohol Group, Control Group, Nicotine Group, Nicotine and Alcohol Group

Primary outcome

Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)
Time frame: Baseline
The DSN-back is a cognitive task used to assess working memory and attention. Participants view a sequence of letters presented on a screen, flanked by either drug-related or neutral images, and are instructed to identify matches occurring N steps earlier. Neural activation during high working memory demand condition (2-back) relative to the low working memory condition (0-back) was investigated. Inconsistent activation patterns across regions may indicate impaired neural processing in regions critical for cognitive control, emotion regulation, and reward processing, commonly reported in substance use disorders. Values closer to 0 (no change) in regions responsible for emotion regulation and cognitive control (e.g., Amygdala, ACC) may indicate reduced task-specific engagement where drug-related processes may be dominating neural activity.
Brain Activation During Resting State MRI.
Time frame: Baseline
This outcome measures resting-state functional connectivity (rsFC) of the striatum using seed-based analysis of resting-state fMRI data. FC values, expressed as Fisher z-transformed correlation coefficients, quantify the strength of synchronization between the striatum seed region and other brain areas. Positive values indicate synchronized activity, while negative values reflect anticorrelation. Altered rsFC of the striatum, a hub for reward processing, habit formation, and executive control, is linked to alcohol and nicotine use disorders and may indicate impaired regulation of cravings and heightened sensitivity to substance-related cues. Investigating rsFC patterns may identify biomarkers of addiction severity, predict treatment outcomes, and inform potential therapeutic targets.
Brain Cortical Thickness Assessed During MRI
Time frame: Baseline
This outcome measures cortical thickness (millimeters) across brain regions using structural MRI. Cortical thickness reflects the integrity of gray matter and is influenced by factors such as neurodegeneration, plasticity, and development. Reductions in cortical thickness, particularly in prefrontal and limbic regions, are associated with impaired cognitive control, emotion regulation, and decision-making in substance use disorders.
Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI
Time frame: Baseline
Fractional Anisotropy (FA) is a scalar metric derived from diffusion-weighted MRI that quantifies the degree of directional dependence (anisotropy) of water diffusion in brain white matter, with values ranging from 0 (isotropic diffusion) to 1 (maximally anisotropic diffusion). Increases in FA may reflect greater white matter organization and integrity, while decreases often indicate microstructural damage, demyelination, or axonal loss. FA measurements were averaged within predefined regions of interest (ROIs) to assess the integrity of white matter in various brain regions associated with cognitive, motor, and emotional processing. Decreased FA in tracts such as the corpus callosum or prefrontal pathways may reflect impaired communication between brain regions involved in reward processing and cognitive control in substance use disorders.

Results and safety

Results posted to the registry on 13 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control Group	31	28
Nicotine Group	28	18
Alcohol Group	13	11
Nicotine and Alcohol Group	33	25

Primary outcome: Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK)

Time frame: Baseline. Mean (Standard Deviation). Unit: Percent signal change

Measure	Control Group n = 26	Nicotine Group n = 8	Alcohol Group n = 5	Nicotine and Alcohol Group n = 17
Anterior Cingulate Cortex	-26.1562 (163.7528)	-45.2123 (142.7251)	18.4989 (119.7023)	-8.8848 (93.3926)
Amygdala	-37.6450 (101.1780)	-72.3998 (160.9536)	-36.6553 (143.9042)	-17.9994 (119.2175)
Hippocampus	-31.8272 (106.1173)	-45.4345 (124.8141)	-69.7126 (115.1060)	-37.1105 (135.3652)
Insula	-0.7322 (152.9914)	-73.3807 (160.7811)	61.6090 (138.2172)	-42.4399 (146.2034)
Medial Orbital Frontal Cortex	-35.9220 (52.9373)	-22.4666 (55.9283)	37.5445 (95.7412)	-12.6343 (42.7803)
Nucleus Accumbens	-56.2479 (193.2017)	-121.6585 (258.8531)	-133.8492 (123.4497)	-40.6751 (112.4257)

Population analysed: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.

Primary outcome: Brain Activation During Resting State MRI.

Time frame: Baseline. Mean (Standard Deviation). Unit: correlation coefficient

Measure	Control Group n = 25	Nicotine Group n = 10	Alcohol Group n = 5	Nicotine and Alcohol Group n = 8
Anterior Cingulate Cortex (ACC)	0.1817 (0.1460)	0.1858 (0.1576)	0.1729 (0.0973)	0.1308 (0.0959)
Amygdala	0.1293 (0.1124)	0.1216 (0.1148)	0.0232 (0.0903)	0.0930 (0.0682)
Hippocampus	0.0391 (0.0998)	0.0746 (0.1068)	0.0255 (0.0791)	0.0348 (0.0609)
Insula	0.2297 (0.1390)	0.3139 (0.1958)	0.2134 (0.1306)	0.2386 (0.1829)
Medial Orbital Frontal Cortex (OFC)	0.0469 (0.0398)	0.0574 (0.0420)	0.0726 (0.0456)	0.0327 (0.0397)
Lateral OFC	0.0769 (0.0739)	0.1212 (0.0826)	0.0969 (0.0587)	0.0770 (0.0655)
Bilateral Middle Frontal Gyrus	-0.0501 (0.0996)	-0.0128 (0.1573)	0.0393 (0.0580)	-0.0184 (0.0974)
Rostral ACC	0.1610 (0.1664)	0.2674 (0.1721)	0.2327 (0.1361)	0.1293 (0.1124)

Population analysed: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.

Primary outcome: Brain Cortical Thickness Assessed During MRI

Time frame: Baseline. Mean (Standard Deviation). Unit: mm

Measure	Control Group n = 29	Nicotine Group n = 12	Alcohol Group n = 9	Nicotine and Alcohol Group n = 22
Left caudal anterior cingulate	2.6111 (0.2171)	2.5421 (0.1780)	2.5472 (0.2005)	2.6560 (0.5697)
Left inferior parietal cortex	2.4885 (0.0862)	2.4414 (0.0675)	2.3881 (0.0586)	2.4132 (0.5030)
Left rostral anterior cingulate	2.7960 (0.1675)	2.7058 (0.1977)	2.7173 (0.1454)	2.7150 (0.5749)
Left rostral middle frontal cortex	2.4701 (0.0898)	2.4315 (0.0752)	2.3740 (0.0794)	2.4406 (0.5069)
Left supramarginal cortex	2.6022 (0.1315)	2.5550 (0.0838)	2.4669 (0.0656)	2.5375 (0.5283)
Right caudal anterior cingulate	2.4662 (0.1935)	2.4350 (0.1495)	2.3582 (0.1392)	2.4452 (0.5130)
Right inferior parietal cortex	2.5510 (0.0803)	2.5175 (0.0953)	2.4377 (0.0324)	2.4774 (0.5158)
Right rostral anterior cingulate	2.8013 (0.1454)	2.6618 (0.2390)	2.6828 (0.1466)	2.7507 (0.5852)

Population analysed: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.

Primary outcome: Brain White Matter Integrity as Assessed by Fractional Anisotropy During MRI

Time frame: Baseline. Mean (Standard Deviation). Unit: Unitless

Measure	Control Group n = 19	Nicotine Group n = 10	Alcohol Group n = 3	Nicotine and Alcohol Group n = 15
Forceps Major	0.4167 (0.1984)	0.3996 (0.1497)	0.4030 (0.1900)	0.4044 (0.1930)
Forceps Minor	0.3794 (0.1809)	0.3657 (0.1374)	0.3574 (0.1685)	0.3589 (0.1718)
Left Anterior Thalamic Radiation	0.3474 (0.1653)	0.3362 (0.1257)	0.3356 (0.1582)	0.3334 (0.1592)
Right Anterior Thalamic Radiation	0.3450 (0.1642)	0.3337 (0.1247)	0.3331 (0.1570)	0.3306 (0.1578)
Left Inferior fronto-occipital fasciculus	0.3536 (0.1684)	0.3388 (0.1268)	0.3383 (0.1595)	0.3374 (0.1614)
Right Inferior fronto-occipital fasciculus	0.3574 (0.1702)	0.3436 (0.1287)	0.3422 (0.1614)	0.3417 (0.1632)
Left Temporal Superior longitudinal fasciculus	0.3535 (0.1683)	0.3389 (0.1269)	0.3392 (0.1600)	0.3387 (0.1620)
Right Temporal Superior longitudinal fasciculus	0.3460 (0.1647)	0.3338 (0.1251)	0.3340 (0.1574)	0.3330 (0.1592)

Population analysed: Participants were removed from analysis due to too much motion, performing the task incorrectly, or did not perform the task during the MRI session.

Adverse events

Time frame: 6 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control Group	0 of 31 (0%)	0 of 31 (0%)	0 of 31
Nicotine Group	0 of 28 (0%)	0 of 28 (0%)	0 of 28
Alcohol Group	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Nicotine and Alcohol Group	0 of 33 (0%)	0 of 33 (0%)	0 of 33

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

William F Hoffman, MD PhD principal investigator

VA Portland Health Care System, Portland, OR

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Alcohol Use Disorder and Nicotine Use Disorder, run by VA Office of Research and Development 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 1 inclusion and 1 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 13 Feb 2025. 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?

Yes. Results are posted in the registry (first posted 13 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Brain Activation During Functional Magnetic Resonance Imaging (fMRI) in Response to a Stress Modulated Cue Induced Craving Task (DSNBACK) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03338933.

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 13 Feb 2025.