Central Cholinergic Dysfunction in Depression: PET Imaging of a Novel Treatment Target With [18F]VAT to Assess the Antidepressant Effect of Nicotine
Trial Snapshot
- Phase
- Phase 4
- Status
- Recruiting
- Sponsor
- Stony Brook University
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Change in Hamilton Depression Rating Scale-17 (HAMD) score.
Study Overview
Brief Summary
In the brain, certain nerve cells communicate using a chemical called acetylcholine. Acetylcholine is thought to be important for several functions including mood, memory and wakefulness. The purpose of this study is to explore the role of these nerve cells in depression. Also, we would like to understand how nicotine, the study drug, works in depression and how it affects these nerve cells. To do this, brain imaging will be used before and after this treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Control
This arm consists of non-depressed participants. These participants will receive one PET scan utilizing tracer [18F] VAT to measure cholinergic terminal density.
Intervention: PET Scan with [18F] VAT (Drug)
Major Depressive Disorder (MDD)
This arm consists of participants diagnosed with Major Depressive Disorder. Participants in the MDD arm will receive interventional treatment for 8 days with transdermal nicotine patches. Participants in the MDD arm will also receive two PET scans with [18F]VAT tracer: one at baseline and one post-treatment.
Intervention: Nicotine transdermal patch (Drug)
Major Depressive Disorder (MDD)
This arm consists of participants diagnosed with Major Depressive Disorder. Participants in the MDD arm will receive interventional treatment for 8 days with transdermal nicotine patches. Participants in the MDD arm will also receive two PET scans with [18F]VAT tracer: one at baseline and one post-treatment.
Intervention: PET Scan with [18F] VAT (Drug)
Outcomes
Primary Outcomes
Change in Hamilton Depression Rating Scale-17 (HAMD) score.
Time Frame: Before and after 8 days of treatment with nicotine.
Description: Comparison of Hamilton Depression Rating Scale-17 score at pretreatment and post-treatment. Minimum score 0, maximum possible score 52, with remission defined as \<=7. The higher the score on the scale, the more severe the degree of depression.
Secondary Outcomes
No secondary outcomes reported
Investigators
Ramin Parsey
Professor of Psychiatry, Director of PET Strategy (M.D., Ph.D.)
Stony Brook University