Participation in other interventional research.
History of penetrating head injury
History of TBI more severe than mild by DVBIC criteria
Diagnosis of a primary or secondary HA disorder other than PTHA
Lifetime history of 5 or more migraine or probable migraine headaches pre-dating mTBI
HAs of any kind of moderate or severe intensity on an average of more than 2 days per month preceding the concussive trauma
Continuous HAs of any kind (i.e., persistent daily HAs with no HA-free period less than 8 hours between attacks)
Acute or serious medical illness or unstable chronic medical illness (e.g., unstable angina, myocardial infarction within 6 months, congestive heart failure, clinically significant or concerning cardiac arrhythmias; preexisting hypotension [systolic blood pressure<110] or orthostatic hypotension [systolic drop >20 mm Hg after 2 min standing accompanied by lightheadedness], chronic renal or hepatic failure, acute pancreatitis, Meniere's disease, or diagnosed but untreated sleep apnea). The eligibility of potential participants having acute serious and/or chronic medical illnesses other than those listed will be evaluated on a case-by-case basis by a study physician, PA-C, or ARNP.
Use of prazosin or other alpha-1 antagonist (including but not limited to alfuzosin, doxazosin, silodosin, tamsulosin, terazosin) for any purpose in the 2 weeks prior to initial screen (P1) visit and prohibited throughout the study
Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist
Active psychosis or psychotic disorder, severe depression (as determined per clinician prescriber judgment), severe psychiatric instability or severe situational life crisis (including evidence of being actively suicidal or homicidal).
Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for any Substance Use Disorder except caffeine-related disorders, or tobacco-related disorders.
History of delirium within the prior 3 months, epilepsy, stroke, dementia, psychotic disorder, or bipolar disorder
Structural brain abnormalities on any prior imaging with associated clinically evident manifestations
Current participation in transcranial magnetic stimulation studies
Women of childbearing potential must not be pregnant, planning to become pregnant during the study period, or nursing.
Participation in a HA support group or other activity such as meditation or yoga intended to mitigate HA or other chronic pain must be stable at least 4 weeks prior to beginning the initial screen (P1) visit and may not be started during the study
Failure to record HA data for at least 80% of days during the Screening Period
Not suitable for study per clinician judgement.
The use of HA rescue or symptom-relieving medications will be allowed during the study. This includes triptans, ergotamines, opioids, simple analgesics (e.g. acetaminophen, aspirin, or non-steroidal anti-inflammatories [NSAIDS], and combination analgesics. Their use will be recorded on the concurrent medication CRF during the Preliminary Screening Period (P1) and throughout the remainder of the study. Randomization of participants will be stratified based on whether their use of HA medications meets ICHD-3 beta criteria for overuse of these medications, as described in section 5.5 below.
Opioid Medications: Use of opioids for treatment of HA or non-HA-related pain or for any other purpose is allowed during the study. Any opioid use would ideally be excluded due to potential confounding effects on interpretation of response to treatment. However, in this population, particularly in Veterans with chronic pain or undergoing minor orthopedic or dental procedures, opioid use is common. Use of opioids, including frequency and dose, will be recorded on the concurrent medication CRF.
Other Medications: Participants who are taking other medications on a routine basis must be on a stable dose for at least 4 weeks prior to the Preliminary Screening Period (P1), and must intend to continue the medication at the same regimen for the duration of the trial unless lack of efficacy, safety, or tolerability dictates otherwise. The following medications are not excluded:
Psychoactive drugs (for example, anticonvulsants, benzodiazepines, antidepressants, sedative/hypnotics),
Antihypertensive medications (including beta-blockers, calcium channel blockers, angiotensin converting enzyme [ACE] inhibitors, and angiotensin receptor blockers),
The use of magnesium in any dose that is prescribed for the purpose of HA prevention or treatment must be stable for at least 4 weeks. The incidental use of magnesium in multi-vitamins, laxatives, etc. is permissible but must be documented.
Hormones (for example, testosterone, estrogen, or progesterone) in any form.
The "as-needed" (prn) use of psychoactive and other drugs such as antibiotics is not excluded; however, such use must be discussed with a clinician prescriber and documented.
The use of butalbital in any form within 4 weeks of beginning the Preliminary Screening Period (P1) through the end of the participant's study involvement is exclusionary.
Participants who have been taking trazodone will undergo a 2-week washout period before the Preliminary Screening Period (P1 visit). Combining prazosin and trazodone may increase the risk of priapism. We have decided to begin the washout period before the Preliminary Screening Period in order to remove any confounding variables while on the headache log and actigraphy.
Sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) will not be permitted during the study drug dose Titration Period, because of increased risk of hypotension in combination with alpha-1 blockers, but will be allowed at half the usual starting dose following the study drug dose Titration Period, per VA prescribing guidelines.
Use of supplements containing nitrates and supplements containing stimulants (such as ephedra) are exclusionary in the two weeks prior to initial screen (P1) visit and prohibited throughout the study. Participants who take these supplements will be asked to discontinue them for a minimum of two weeks before the Preliminary Screening Period (P1 visit)..
Use of prescribed stimulants (such as amphetamine or dextroamphetamine containing medications) is exclusionary in the 2 weeks prior to the initial screen (P1) visit and prohibited throughout the study. Participants who take these medications will be asked to discontinue them for a minimum of 2 weeks before the Preliminary Screening Period.

NCT02965027_exc_T2
Condition
penetrating head injury
NCT02965027_exc_T3
Condition
TBI
NCT02965027_exc_T4
Value
more severe than mild
NCT02965027_exc_T5
Measurement
DVBIC criteria
NCT02965027_exc_T6
Qualifier
primary
NCT02965027_exc_T7
Qualifier
secondary
NCT02965027_exc_T8
Condition
HA disorder
NCT02965027_exc_T9
Condition
PTHA
NCT02965027_exc_T10
Negation
other than
NCT02965027_exc_T11
Scope
primary or secondary
NCT02965027_exc_T12
Observation
Lifetime history
NCT02965027_exc_T13
Multiplier
5 or more
NCT02965027_exc_T14
Condition
migraine
NCT02965027_exc_T15
Qualifier
probable
NCT02965027_exc_T16
Condition
migraine
NCT02965027_exc_T17
Temporal
pre-dating mTBI
NCT02965027_exc_T18
Procedure
mTBI
NCT02965027_exc_T19
Reference_point
mTBI
NCT02965027_exc_T20
Scope
migraine or probable migraine
NCT02965027_exc_T21
Condition
HAs
NCT02965027_exc_T22
Qualifier
moderate or severe intensity
NCT02965027_exc_T23
Multiplier
average of more than 2 days per month
NCT02965027_exc_T24
Temporal
preceding the concussive trauma
NCT02965027_exc_T25
Condition
HAs
NCT02965027_exc_T26
Qualifier
Continuous
NCT02965027_exc_T27
Qualifier
persistent
NCT02965027_exc_T28
Multiplier
daily
NCT02965027_exc_T29
Measurement
e period less n attacks)
Acut
NCT02965027_exc_T30
Value
less than 8 hours
NCT02965027_exc_T31
Negation
no
NCT02965027_exc_T32
Condition
HAs
NCT02965027_exc_T33
Qualifier
Acute
NCT02965027_exc_T34
Qualifier
serious
NCT02965027_exc_T35
Condition
medical illness
NCT02965027_exc_T36
Qualifier
unstable
NCT02965027_exc_T37
Condition
chronic medical illness
NCT02965027_exc_T38
Condition
unstable angina
NCT02965027_exc_T39
Condition
myocardial infarction
NCT02965027_exc_T40
Temporal
within 6 months
NCT02965027_exc_T41
Condition
congestive heart failure
NCT02965027_exc_T42
Qualifier
clinically significant
NCT02965027_exc_T43
Qualifier
concerning
NCT02965027_exc_T44
Condition
cardiac arrhythmias
NCT02965027_exc_T45
Temporal
preexisting
NCT02965027_exc_T46
Condition
hypotension
NCT02965027_exc_T47
Measurement
systolic blood pressure
NCT02965027_exc_T48
Value
<110
NCT02965027_exc_T49
Condition
orthostatic hypotension
NCT02965027_exc_T50
Measurement
systolic drop
NCT02965027_exc_T51
Value
>20 mm Hg
NCT02965027_exc_T52
Temporal
after 2 min standing
NCT02965027_exc_T53
Condition
lightheadedness
NCT02965027_exc_T54
Condition
 renal or he , acute
NCT02965027_exc_T55
Condition
hepatic failure
NCT02965027_exc_T56
Condition
acute pancreatitis
NCT02965027_exc_T57
Condition
Meniere's disease
NCT02965027_exc_T58
Condition
sleep apnea
NCT02965027_exc_T59
Qualifier
untreated
NCT02965027_exc_T61
Scope
Acute or serious
NCT02965027_exc_T62
Scope
clinically significant or concerning
NCT02965027_exc_T63
Scope
systolic drop >20 mm Hg after 2 min standing accompanied by lightheadedness
NCT02965027_exc_T64
Scope
unstable angina, myocardial infarction within 6 months, congestive heart failure, clinically significant or concerning cardiac arrhythmias; preexisting hypotension [systolic blood pressure<110] or orthostatic hypotension [systolic drop >20 mm Hg after 2 min standing accompanied by lightheadedness], chronic renal or hepatic failure, acute pancreatitis, Meniere's disease, or diagnosed but untreated sleep apnea
NCT02965027_exc_T65
Scope
Acute or serious medical illness or unstable chronic medical illness
NCT02965027_exc_T66
Drug
prazosin
NCT02965027_exc_T67
Qualifier
other
NCT02965027_exc_T68
Drug
alpha-1 antagonist
NCT02965027_exc_T69
Drug
alfuzosin
NCT02965027_exc_T70
Drug
doxazosin
NCT02965027_exc_T71
Drug
silodosin
NCT02965027_exc_T72
Drug
tamsulosin
NCT02965027_exc_T73
Drug
terazosin
NCT02965027_exc_T74
Temporal
in the 2 weeks prior to initial screen (P1) visit
NCT02965027_exc_T75
Reference_point
initial screen (P1) visit
NCT02965027_exc_T76
Scope
prazosin or other alpha-1 antagonist
NCT02965027_exc_T77
Scope
alfuzosin, doxazosin, silodosin, tamsulosin, terazosin
NCT02965027_exc_T78
Condition
Allergy
NCT02965027_exc_T79
Condition
adverse reaction
NCT02965027_exc_T80
Temporal
previous
NCT02965027_exc_T81
Drug
prazosin
NCT02965027_exc_T82
Drug
alpha-1 antagonist
NCT02965027_exc_T83
Qualifier
other
NCT02965027_exc_T84
Scope
prazosin or other alpha-1 antagonist
NCT02965027_exc_T85
Scope
Allergy or previous adverse reaction
NCT02965027_exc_T86
Condition
psychotic disorder
NCT02965027_exc_T87
Condition
psychosis
NCT02965027_exc_T88
Qualifier
Active
NCT02965027_exc_T89
Condition
severe depression
NCT02965027_exc_T90
Condition
psychiatric instability
NCT02965027_exc_T91
Qualifier
severe
NCT02965027_exc_T92
Condition
situational life crisis
NCT02965027_exc_T93
Qualifier
severe
NCT02965027_exc_T94
Condition
suicidal
NCT02965027_exc_T95
Condition
homicidal
NCT02965027_exc_T96
Scope
suicidal or homicidal
NCT02965027_exc_T97
Condition
Substance Use Disorder
NCT02965027_exc_T98
Condition
caffeine-related disorders
NCT02965027_exc_T99
Negation
except
NCT02965027_exc_T100
Condition
tobacco-related disorders
NCT02965027_exc_T101
Scope
caffeine-related disorders, or tobacco-related disorders
NCT02965027_exc_T102
Measurement
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria
NCT02965027_exc_T103
Value
Meets
NCT02965027_exc_T104
Condition
delirium
NCT02965027_exc_T105
Temporal
within the prior 3 months
NCT02965027_exc_T106
Condition
epilepsy
NCT02965027_exc_T107
Condition
stroke
NCT02965027_exc_T108
Condition
dementia
NCT02965027_exc_T109
Condition
psychotic disorder
NCT02965027_exc_T110
Condition
bipolar disorder
NCT02965027_exc_T111
Condition
Structural brain abnormalities
NCT02965027_exc_T112
Procedure
imaging
NCT02965027_exc_T113
Temporal
prior
NCT02965027_exc_T114
Qualifier
any
NCT02965027_exc_T115
Qualifier
clinically evident
NCT02965027_exc_T116
Condition
manifestations
NCT02965027_exc_T117
Procedure
transcranial magnetic stimulation studies
NCT02965027_exc_T118
Temporal
Current
NCT02965027_exc_T119
Condition
childbearing potential
NCT02965027_exc_T120
Person
Women
NCT02965027_exc_T121
Negation
not be
NCT02965027_exc_T122
Condition
pregnant
NCT02965027_exc_T123
Mood
planning to become
NCT02965027_exc_T124
Condition
pregnant
NCT02965027_exc_T125
Temporal
during the study period
NCT02965027_exc_T126
Condition
nursing
NCT02965027_exc_T127
Scope
pregnant, planning to become pregnant during the study period, or nursing
NCT02965027_exc_T128
Scope
Women of childbearing potential
NCT02965027_exc_T129
Procedure
Participation in a HA support group
NCT02965027_exc_T130
Procedure
meditation
NCT02965027_exc_T131
Procedure
yoga
NCT02965027_exc_T133
Observation
Failure to record HA data
NCT02965027_exc_T134
Multiplier
for at least 80% of days
NCT02965027_exc_T135
Temporal
during the Screening Period
NCT02965027_exc_T139
Drug
medications
NCT02965027_exc_T140
Multiplier
on a routine basis
NCT02965027_exc_T141
Qualifier
stable dose
NCT02965027_exc_T142
Temporal
for at least 4 weeks prior to the Preliminary Screening Period (P1)
NCT02965027_exc_T143
Qualifier
other
NCT02965027_exc_T144
Scope
other medications on a routine basis
NCT02965027_exc_T151
Drug
butalbital
NCT02965027_exc_T152
Temporal
within 4 weeks of beginning the Preliminary Screening Period (P1)
NCT02965027_exc_T154
Drug
Sildenafil
NCT02965027_exc_T155
Drug
Viagra
NCT02965027_exc_T156
Drug
tadalafil
NCT02965027_exc_T157
Drug
Cialis
NCT02965027_exc_T158
Drug
vardenafil
NCT02965027_exc_T159
Drug
Levitra
NCT02965027_exc_T160
Drug
avanafil
NCT02965027_exc_T161
Drug
Stendra
NCT02965027_exc_T162
Temporal
during the study drug dose Titration Period
NCT02965027_exc_T163
Scope
Sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra)
NCT02965027_exc_T164
Drug
nitrates
NCT02965027_exc_T165
Drug
stimulants
NCT02965027_exc_T166
Drug
ephedra
NCT02965027_exc_T167
Temporal
in the two weeks prior to initial screen (P1) visit
NCT02965027_exc_T168
Scope
nitrates and supplements containing stimulants (such as ephedra)
NCT02965027_exc_T169
Drug
prescribed stimulants
NCT02965027_exc_T170
Drug
amphetamine
NCT02965027_exc_T171
Drug
dextroamphetamine
NCT02965027_exc_T172
Scope
amphetamine or dextroamphetamine
NCT02965027_exc_T173
Temporal
in the 2 weeks prior to the initial screen (P1) visit