Prazosin and CSF Biomarkers in mTBI

Inclusion Criteria:

- Age 21 years

- Ability to complete psychometric and other clinical assessments in English

- No clinically significant laboratory abnormalities at screen

- Platelet count >100,000/mm2 within two weeks of lumbar puncture (LP)

- Body mass index (BMI) between 18 and 36 inclusive (BMIs outside this range affect CSF
biomarker measurements and/or make LPs for CSF collection difficult to perform).

- Women of childbearing potential must agree to abstain from sexual relations that could
result in pregnancy or use an effective method of birth control acceptable to both
participant and the study clinician during the study. Men are not required to use
contraception during the study

- Meeting criteria for at least one of the following:

1. History of mild or moderate TBI:

- Exposure to at least one blast or experiencing at least one collision of the head
associated with acute symptoms that meet VA/DoD criteria for mild or moderate TBI
(loss of consciousness, if present, <24 hours; posttraumatic amnesia, if present, <1
week; Glasgow Coma Scale (if available) 9-15) ->6 months since last TBI. 2. Documented
diagnosis of PTSD related to combat trauma (from any conflict)

Exclusion Criteria:

Medical

- History of severe TBI (Glasgow Coma Scale (if available) <9, loss of consciousness >24
hours, posttraumatic amnesia >1 week)

- Acute or unstable chronic medical illness, including unstable angina, recent
myocardial infarction (within 6 months), congestive heart failure, preexisting
hypotension (systolic <110) or orthostatic hypotension (systolic drop > 20mmHg after
two minutes standing or any drop accompanied by dizziness), autoimmune disorders;
insulin-dependent diabetes

- Chronic renal or hepatic failure, acute pancreatitis, Meniere's disease, benign
positional vertigo, narcolepsy, or diagnosed untreated sleep apnea (sleep apnea
currently being treated is not exclusionary).

- Contraindications to LP (e.g., spinal cord injury; deformity, severe disease or
infection in the region of the lumbosacral spine; bleeding tendency, clotting
abnormalities, use of anticoagulant medications, or platelet count <100,000/mm2);
trauma or infection in the 4 weeks before LP

- Current pregnancy or lactation. Women of childbearing potential must agree to abstain
from sexual relations that could result in pregnancy or use an effective method of
birth control acceptable to both participant and the study clinician during the study.
Men are not required to use contraception during the study.

Psychiatric/Behavioral

- Meets DSM(IV or 5, depending on what evaluative method was used in this subject)
criteria for current schizophrenia, schizoaffective disorder, other specified or
unspecified psychotic disorder, delirium, or any DSM cognitive disorder

- Current substance use disorder (except caffeine-related disorders, tobacco-related
disorders, or cannabis intoxication) other than in remission for at least 3 months.
The use of cannabis other than that meeting criteria for cannabis use disorder is not
exclusionary. Use of cannabis will be documented.

- Current use of any stimulant, including prescribed stimulant medications

- Current use (within the past 1 month, ongoing, or expected during the study period) of
any drugs that are illegal under Washington state law.

- Severe psychiatric instability or severe situational life crises, including evidence
of being actively suicidal or homicidal, or any behavior which poses an immediate
danger to participant or others.

Medications/Therapies

- Current use of prazosin or other alpha-1 antagonist or trazodone, or use of such agent
within the 3 month period prior to when the baseline 2 visit would be scheduled (a
3-month washout is required due to the potential effects it may have on the biomarker
measurements).

- Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist

- Use of exclusionary medications in the 4 weeks prior to screening: selected CNS-acting
medications; antipsychotics, anti-Parkinson's disease medications and CNS stimulants;
Coumadin or other medications affecting coagulation and/or inflammation (low-dose
aspirin and use of NSAIDs for pain will not be exclusionary); potent immune-modulating
medications, such as hydrocortisone or methotrexate; anti-HIV medications.

- Use of avanafil (Stendra), sildenafil (Viagra), tadalafil (Cialis), and vardenafil
(Levitra) will be not be permitted during the study dose titration period because of
increased risk of hypotension in combination with alpha-1 blockers, but will be
allowed at 1/2 the usual starting dose following dose titration

- Current use of stimulants or nitrates, or of alternative medications or supplements
with stimulant properties (e.g., ephedra) or vasodilatory properties (e.g., nitrate
containing supplements)

- Recent evidence based trauma- or sleep-focused psychotherapy, such as Prolonged
Exposure therapy (PE), Cognitive Processing Therapy (CPT), Eye Movement
Desensitization and Reprogramming (EMDR), Cognitive Behavioral Therapy for Insomnia
(CBTi) or Image Rehearsal and Rescripting therapy for nightmares. These therapies must
have been completed > 4 weeks before first baseline assessment visit (study visit 2).

Other

- Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist

- Receiving another medication in another interventional study