PET with [18F]VAT to see how nicotine affects brain acetylcholine in depression

Central Cholinergic Dysfunction in Depression: PET Imaging of a Novel Treatment Target With [18F]VAT to Assess the Antidepressant Effect of Nicotine

We will use PET scans with the [18F]VAT tracer to see if a nicotine patch changes acetylcholine-related brain signals in adults with major depressive disorder.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 14 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Stony Brook University (other)
• Locations: 1 site (Stony Brook, New York)
• Trial ID: NCT07095205 on ClinicalTrials.gov

What this trial studies

This interventional, Phase 4 protocol uses PET imaging with the [18F]VAT tracer before and after administration of a transdermal nicotine patch to map cholinergic nerve-cell activity. The trial enrolls adults aged 18–65 with current major depressive disorder (MADRS ≥29) as well as non-depressed control participants. Imaging comparisons between pre- and post-nicotine scans aim to show how nicotine alters vesicular acetylcholine transporter–related signals in the brain. Safety monitoring and screening for recent nicotine use or medications that affect cholinergic function are included in the protocol.

Who should consider this trial

Good fit: Adults 18–65 who are currently in a major depressive episode with a MADRS score of at least 29 and who can give informed consent are ideal candidates, while healthy non-depressed adults are enrolled as controls.

Not a fit: People with milder depression below the MADRS cutoff, significant active medical illness, recent nicotine use, or who require medications that alter cholinergic levels are unlikely to receive benefit from participation.

Why it matters

Potential benefit: If successful, the results could clarify how nicotine affects cholinergic circuits in depression and help guide development of treatments that target acetylcholine signaling.

How similar studies have performed: Prior PET and pharmacology studies have implicated cholinergic systems and nicotine in mood regulation, but use of the [18F]VAT tracer for this purpose is relatively new with limited prior validation in depression.

Eligibility criteria

Inclusion Criteria:

For Non-Depressed Participants:

* Age range 18 to 65 years old.
* Capacity to consent (able to read, understand, and sign informed consent).

For Participants with MDD

* Age range 18 to 65 years old.
* Capacity to consent (able to read, understand, and sign informed consent).
* Major Depressive Disorder (MDD) as primary diagnosis and currently in a major depressive episode
* Score of at least 29 on the Montgomery-Asberg Depression Rating Scale (MADRS).

Exclusion Criteria:

For Non-Depressed Participants:

* Nicotine use, including tobacco, e-cigarettes, nicotine patch, nicotine gum, within the past year \[except for occasional users, who cannot use nicotine products in the week before the scan\].
* Need for use of medication during the study that will affect cholinergic levels.
* Problematic drug/alcohol use that is judged sufficient to interfere with study procedures during the treatment period or impact participant safety.
* Significant active physical illness or neurological deficit that may affect brain function or imaging.
* Significant eye conditions such as keratoconus and/or need for rigid contact lenses.
* Current or lifetime history of a major psychiatric diagnosis.
* Any MRI contraindications, including recent tattoos, metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI.
* Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is pregnant, currently breastfeeding, or planning to conceive during the course of study participation.
* Blood donation within 8 weeks of the \[18F\]VAT scan.

For Participants with MDD

* Nicotine use, including tobacco, e-cigarettes, nicotine patch, nicotine gum, within the past year \[except for occasional users, who cannot use nicotine products in the week before the scan\].
* Currently on effective antidepressant medications or need for use of medications that target the cholinergic system.
* Problematic drug/alcohol use that is judged sufficient to interfere with study procedures during the treatment period or impact participant safety.
* Significant active physical illness or neurological deficit that may affect the brain function or imaging.
* Significant eye conditions such as keratoconus and/or need for rigid contact lenses.
* Current or lifetime major psychiatric diagnosis other than MDD.
* Life-time history of psychosis or current psychosis.
* Significant risk for suicide.
* Any MRI contraindications, including recent tattoos, metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI.
* Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is pregnant, currently breastfeeding, or planning to conceive during the course of study participation.
* Blood donation within 8 weeks of the \[18F\]VAT scan.

Where this trial is running

Stony Brook, New York

• Stony Brook University: Dept of Psychiatry — Stony Brook, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Ramin Parsey, MD, PhD — Stony Brook University
• Study coordinator: Julianna Lizzul

Conditions: Major Depressive Disorder