Striatal Dopamine Transporter Density in Post-Traumatic Stress Disorder (PTSD)

This research study is being done to try to find a way to accurately diagnose post-traumatic stress syndrome (PTSD) in combat veterans.Diagnostic biomarkers have made invaluable contributions to the diagnosis and treatment monitoring of many diseases and disorders. Unfortunately, PTSD currently lacks a reliable and compelling clinically-relevant biomarker. The absence of a viable biomarker impairs efficient and confident diagnosis of PTSD, with diminished effective care options often resulting.

Study Overview

• Status: Not yet recruiting
• Conditions: Post-traumatic Stress Disorder
• Intervention / Treatment: Diagnostic test: MRI using DaTscan

Detailed Description

The possibility of developing PTSD exists when a person is exposed to death, threatened death, or actual or threatened serious injury either by direct exposure, witnessing the trauma, or learning that a close friend was exposed to this type of trauma. Rates of PTSD in military personnel returning from armed conflicts may be greater than 30%. The diagnosis of PTSD is based on a psychiatrist's or psychologist's assessment of the symptoms reported by the veteran and others, such as family or friends.The veteran with PTSD may struggle with thoughts and feelings that "don't make sense" or he or she believes are just not "warrior-like". The veteran eventually sees a mental health professional but may downplay the symptoms and fail to be correctly diagnosed. This places these men and women at risk for suicide. Dopamine is a substance found in our brains that has a role in regulating fear and stress as well as other emotional responses. There have been studies that have shown a protein in blood called dopamine transporter (DAT) moves dopamine from one place to another in our brain. Studies have shown that the level of DAT present has a role in PTSD. In this research, the researchers will evaluate the usefulness of a type of radioactive drug (DaTscan) which attaches to DAT and then allows the researchers to take pictures of the brain using a camera called a gamma camera. This will produce images called single photon emission computed tomography (SPECT). The researchers are looking for a difference in these pictures in those with PTSD and veterans without PTSD, and hope this can be used to help diagnose PTSD in the future.The brain MRI is done to make sure there is not anything abnormal in the structure of the brain that could interfere with the DaTScan pictures and to accurately locate specific regions of the brain where the DaTScan pictures are especially important. The MRI will also be used to look at natural nerve connections in the brain using functional MRI or fMRI. The researchers will use fMRI to look for possible connection differences in brains of people with PTSD and without PTSD. The DaTscan requires a drug, called a radiotracer given through an intravenous (IV) catheter. This drug is radioactive and a small amount of it will be absorbed by the thyroid gland, so Lugol's solution will be used to block uptake into the thyroid. The length of time to complete the entire DaTscan process is approximately 5 ½ hours. This includes time to receive the drug, then a 3 hour break followed by about 45 minutes to take the pictures. The tracer will collect in part of the brain and give off radiation (gamma rays). A gamma camera will produce pictures of the brain.The MRI process will take approximately 1 hour, including a questionnaire about metal or implants in the subject's body. Brain scanning will last for about 30 minutes.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea Garcia, MBA; Phone Number: 602-406-9769; Email: andrea.garcia2@dignityhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 37 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males
• Diagnosed with PTSD (n=25) or designated combat-experienced controls (n=25)

Exclusion Criteria:

• Head trauma resulting in loss of consciousness
• Co-morbid DSM IV Axis I psychiatric disorder
• hyper- or hypo-thyroidism, neurological motor deficits (e.g. Parkinsonism, tremor)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PTSD Diagnosed; Veterans exposed to combat and diagnosed with PTSD. MRI using DaTscan.	Diagnostic test: MRI using DaTscan; A standard, non-contrast-enhanced structural/anatomic brain MRI will be performed. It will be used to exclude potential subjects and controls with significant and potentially confounding structural/anatomic findings. It will also be used as an "anatomic overlay" with the functional DaTscan image to aid in anatomic/physiologic correlation. At the same imaging session, a brief functional MRI (not requiring the subject to perform any tasks) will also be performed.
Experimental: Designated Combat-Experienced Controls; Veterans exposed to combat, but never diagnosed with PTSD. MRI using DaTscan.	Diagnostic test: MRI using DaTscan; A standard, non-contrast-enhanced structural/anatomic brain MRI will be performed. It will be used to exclude potential subjects and controls with significant and potentially confounding structural/anatomic findings. It will also be used as an "anatomic overlay" with the functional DaTscan image to aid in anatomic/physiologic correlation. At the same imaging session, a brief functional MRI (not requiring the subject to perform any tasks) will also be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DaTscan intensity	Visually recognizable increases in striatal DaTscan intensity in PTSD patients.	within 30 days of MRI
Quantifiable differences	Quantifiable differences in global and regional DAT density in PTSD patients and combat-experienced controls.	within 30 days of MRI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Striatal correlations	Global and regional striatal correlations of DAT density with elements of the psychological/psychiatric evaluation (i.e. psychological/ psychiatric symptoms). For example, the researchers will examine the correlation of DAT density with sleep disturbance.	within 60 days of entry into study

Collaborators and Investigators

• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Investigators: Principal Investigator: Frank V Schraml, MD, St. Joseph's Hospital and Medical Center, Phoenix

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 25, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: biomarker; post-traumatic stress disorder; dopamine
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: PHXB-17-0104-71-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes