Clinical trial NCT02927288: Identifying Biomarkers That Distinguish PTSD and mTBI Using Advanced Magnetic Resonance Spectroscopy
Official title: Identifying Biomarkers That Distinguish Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury Using Advanced Magnetic Resonance Spectroscopy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Post-Traumatic Stress Disorders
Brain Injuries
Keywords: PTSD, mTBI
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: United States Army Research Institute of Environmental Medicine
First posted: 2016-10-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total of 330 men and women from the Massachusetts National Guard, Active Duty Army, and veterans in the New England area and Brigham and Women's Hospital, Boston as well as healthy military and civilians will take part in this study.

Brief summary: The purpose of this study is to develop a new test to help diagnose mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) in soldiers. Chemicals in the brain will be measured using a Magnetic Resonance Spectroscopy (MRS) scan. In the study, the investigators will compare the information they obtain from scans of participants with mTBI, PTSD or both, to scans from healthy volunteers to understand the differences between these groups. If the results can tell the difference between participants with mTBI and PTSD, the investigators should be able to help safely diagnose patients in the future.

Detailed description: Soldiers from the US Army, with well characterized diagnosis of mTBI or PTSD, will be recruited in the first year as will age-matched healthy controls from the military and civilian populations. MRI, single voxel MRS, and two-dimensional correlated spectroscopy (2D COSY) MRS will be acquired from each participant at the Brigham and Women's Hospital (BWH). This data will be anonymized and transferred to the Draper Laboratories. Biomarkers for each disease will be identified by comparison with control data. These biomarkers will then be fed into classifiers that will then be validated with a similar cohort acquired in the second year. The second cohort of subjects will then be incorporated into the classifier algorithms for a stronger and more robust classification from which a diagnostic test will emerge. To test this diagnostic evaluation the data analysis by both BWH and Draper labs will be blinded to the characterization of the participants and from the MRS results, the investigators will predict if the participant has mTBI, PTSD, both, or neither. Finally, all data will then be fused into the algorithms to provide a final classifier. The results of the final classifier will then be correlated with clinical, neuropsychological, and neuroanatomical indices of mTBI and PTSD. These correlations will provide the most complete biochemical analysis of mTBI and PTSD which may lead to insight into alternate pathways for drug development.

Eligibility criteria: Inclusion Criteria:

1. Between the ages of 18 and 55
2. Male and female
3. High School diploma or General Educational Development (GED) equivalent

Exclusion Criteria:

1. History of brain tumor, epilepsy, dementia, and other neurological disorders
2. History of psychotic, bipolar, or other mental disorder aside from PTSD
3. Substance abuse and/or use within the past month of skeletal muscle relaxants, narcotics, anticonvulsants, neuroleptics, benzodiazepines, cerebral stimulants, sedatives, or hypnotics during the month prior to testing, or a "dirty" urine specimen (i.e., containing amphetamines, barbiturates, cocaine, opiates, benzodiazepines, methaqualone, propoxyphene, phencyclidine, methadone, or cannabinoids)
4. Alcohol use 24 hours prior to testing. Subjects will be asked to abstain 24 hours in advance as alcohol can be detected in the MRS spectrum as a multiplet at 1.5 ppm.
5. Inability to give informed consent for participation
6. Any contraindications for MR imaging and spectroscopy

   1. electrical implants such as cardiac pacemakers or perfusion pumps
   2. ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
   3. ferromagnetic objects such as jewelry or metal clips in clothing
   4. any greater than normal potential for cardiac arrest
   5. pregnancy (female of childbearing age and are still having your menstrual periods will be asked to give a urine sample for a pregnancy test that will be administered by the technologist).

Primary outcomes:
measure: NAA to Creatine (NAA/Cr) Ratio (no units)
timeFrame: One year
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Alexander Lin, PhD
role: PRINCIPAL_INVESTIGATOR
References: