Imaging brain changes in PTSD and Alcohol Use Disorder

Imaging Traumatic Stress and Alcohol Use Disorder With [18F]Bavarostat

This study is testing if brain imaging can help us understand how a specific marker is related to PTSD and Alcohol Use Disorder in people who have these conditions.

Quick facts

• Study type: Observational
• Enrollment: 150 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Yale University (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT06371404 on ClinicalTrials.gov

What this trial studies

This study aims to utilize Positron Emission Tomography (PET) imaging with the radiotracer [18F]Bavarostat to investigate the expression of the epigenetic marker Histone Deacetylase 6 (HDAC6) in individuals with Post-Traumatic Stress Disorder (PTSD), Alcohol Use Disorder (AUD), or both. A total of 150 subjects will undergo MRI and PET imaging, along with behavioral and cognitive assessments, to explore the relationship between HDAC6 levels and clinical variables. The study will compare HDAC6 expression in affected individuals against healthy control groups to better understand the neurobiological underpinnings of these disorders.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 70 with a current diagnosis of PTSD or AUD, or those with both conditions.

Not a fit: Patients without a diagnosis of PTSD or AUD, or those who do not meet the study's health criteria, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to targeted treatment developments for PTSD and Alcohol Use Disorder based on biological markers.

How similar studies have performed: While there have been numerous preclinical studies on stress and addiction, this approach using HDAC6 imaging in humans is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Willing and able to give voluntary written informed consent
2. Is able to read and write, able to communicate effectively with the investigator, and comply with all study requirements, restrictions, and directions of the research staff
3. Men or women, aged 18 to 70, at screening
4. In good general health as evidenced by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests
5. Participants with PTSD will have a current diagnosis of PTSD according to DSM-5 criteria (CAPS-5 ascertained diagnosis, confirmed by the Principal Investigators. TC subjects must have a DSM-5 criteria traumatic event with no PTSD diagnosis
6. Participants with AUD will have a current diagnosis of AUD according to DSM-5 criteria (i.e., SCID-5 ascertained diagnosis, confirmed by the Principal Investigators);
7. Participants with AUD will meet the following drinking criteria: males will drink \> 14 drinks per week and exceed 4 drinks per day at least twice per week; females will drink \> 7 drinks per week and exceed 3 drinks per day at least twice per week. They must meet drinking criteria during a consecutive 30-day period within the 90 days prior to intake.
8. Healthy subjects will have no current or past diagnosis of AUD or other significant substance use disorder. They will drink less than 5 alcoholic drinks per week with no heavy drinking days (i.e., \>4 drinks/day for men; \>3 drinks/day for women) in the last 30 days;

Exclusion Criteria:

1. Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology that would impact the integrity of the data (note that elevated liver enzymes for individuals with AUD will not be exclusionary)
2. Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder;
3. Current significant psychiatric disorder including severe substance use disorder (other than alcohol or tobacco use disorders\*), and past or current psychotic symptoms,
4. Regular use in the past 6 months of any prescription, psychoactive or herbal medications (e.g., antidepressants, antipsychotics, anxiolytics) that would impact the integrity of the data (e.g., naltrexone); No subject will be asked to stop taking medication to participate in the study;
5. Pregnancy or lactation
6. Blood donation within eight weeks of the start of the study.
7. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).
8. Unable to safely discontinue or hold aspirin and other NSAID use
9. MRI incompatible implants (i.e., such as pacemaker, artificial joints, non-removable body piercings) and other contraindications for MRI, such as claustrophobia, having implanted or embedded metal objects/fragments or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist).
10. Participation in other research studies involving inonizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for healthy volunteers.
11. Subject who has current, past, or anticipated exposure to radiation in the work place within one year of the proposed research scans that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.
12. Has any condition that, in the opinion of the investigator, would prevent compliance with the study protocol.
13. History of complicated alcohol withdrawal including history of delirium tremens; seizure, hospitalization for withdrawal.
14. Alcohol intoxication at time of screening.
15. A CIWA score ≥8 at intake or on scan day.
16. Subjects who are, in the opinion of the study physician, unable to safely abstain from alcohol overnight prior to their study visits.

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Study coordinator: Kelly Cosgrove

Conditions Alcohol Use Disorder; Post Traumatic Stress Disorder