Post-Traumatic HeadachePhase 4NCT02965027
Prazosin for Post-Concussive Headaches
A Phase 4 study testing Prazosin in people with Post-Traumatic Headache, run by Seattle Institute for Biomedical and Clinical Research at 2 sites in United States.
Trial summary
Mild traumatic brain injury (mTBI) caused by blast effects of explosive devices has been called the "signature injury" of soldiers who served in the Iraq and Afghanistan conflicts. mTBI can also occur from impact or hitting the head on an object or the ground. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-Traumatic Headache
- What is being tested?
- Prazosin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Nov 2016to 7 Jun 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female Active-duty Servicemembers (SMs) or Veterans aged 18 or older who are in good general health.
- History of blast and/or impact head trauma mild traumatic brain injury (mTBI) meeting Defense and Veterans Brain Injury Center (DVBIC) mTBI criteria.
- o Mild TBI is defined as an injury to the head causing at least one of the following: alteration in consciousness (for up to 24 hours after the injury), loss of consciousness (0-30 minutes), and/or post-traumatic amnesia (up to 1 day post-injury). If available, the Glasgow Coma Scale score must be 13-15, and head imaging findings (if imaging was performed) must be negative.
- Frequent headaches (HAs) that started within 3 months after a head injury or marked worsening (a two-fold or greater increase in frequency and/or severity) of pre-existing headaches within 3 months of head injury.
- HAs either 1) must last 4 or more hours a day and reach a moderate to severe intensity at any point during the headache, or 2) may be of any severity or duration if the participant takes a medication or other agent in an effort to stop or treat a headache.
- HAs meeting these criteria must have been present on average at least 8 days per 4-week period and occurring at a stable level by self-report for at least 3 months prior to the Initial Screening Visit. The 4-week HA frequency/severity criteria must be confirmed during the Preliminary Screening Period.
- Participants 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 clinician prescriber during the study. Participants who are not of childbearing potential are not required to use contraception during the study.
- Participants must have English fluency sufficient to complete study measures.
Who cannot join
- Participation in other interventional research.
- History of penetrating head injury
- History of TBI more severe than mild by DVBIC criteria
- A primary non migraine and/or tension-type HA disorder (for example hemicrania continua; cluster) that accounts for the majority of current symptoms.
- HAs of any kind of moderate or severe intensity on an average of more than 4 days per month preceding the concussive trauma
- 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, or acute pancreatitis. 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, physician assistant - certified (PA-C), or advanced registered nurse practitioner (ARNP).
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- 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.
- Medication-and other Treatment-Related Considerations:
- 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 case report form (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 International Classification of Headache Disorders 3rd addition (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.
- Cannabis: The use of cannabis in any form is not excluded unless its use meets criteria for Cannabis Use Disorder. All use of cannabis will be documented.
- Other Medications: Participants who are using other medications or treatments 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 and treatments 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. 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.
- Onabotulinum toxin A and nerve block injections for the purpose of HA prevention are permissible if the treatment response has been stable during the two most recent treatment cycles.
- The "as-needed" (prn) use of any non-exclusionary medications is allowed; 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA Puget Sound Health Care System
Seattle, Washington, 98108
Madigan Army Medical Center
Tacoma, Washington, 98433
About this study
Official title: Prazosin for the Prophylaxis of Chronic Post-Traumatic Headaches in OEF/OIF/OND Service Members and Veterans With Mild TBI
Mild traumatic brain injury (mTBI) caused by blast effects of explosive devices has been called the "signature injury" of soldiers who served in the Iraq and Afghanistan conflicts. mTBI can also occur from impact or hitting the head on an object or the ground. Although termed "mild" in comparison to major brain injuries, people with mTBI can have problems with their memory and concentration. People with mTBI can also find they are more irritable, have more anxiety, and have trouble with their mood and sleep.
The purpose of this study is to see if a medication called prazosin can help treat chronic headaches in people with mTBI. The Food and Drug Administration (FDA) has approved prazosin for treating people with high blood pressure. At this time, the FDA has not approved prazosin in the treatment of mTBI or headaches. Some people who have posttraumatic stress disorder (PTSD) and have been taking prazosin for their medical conditions or who have taken it in research studies have said they have fewer headaches.
Read the detailed description
Background and Rationale: Headaches following mild traumatic brain injury (mTBI) are common, can be refractory to standard therapies, and may persist and worsen to become a debilitating chronic pain syndrome. The purpose of this study is to evaluate the centrally acting alpha-1 adrenoreceptor (AR) antagonist drug prazosin as a prophylactic treatment for chronic posttraumatic headaches (PTHAs). The impetus for this study comes from a large open-label case series in Iraq and Afghanistan Veterans with mTBI and PTHAs and data from a placebo-controlled trial evaluating use of prazosin for posttraumatic stress disorder (PTSD) in active-duty Servicemembers (SMs). Findings from these studies showed that in addition to decreasing PTSD-related symptoms and improving sleep quality, prazosin decreased the frequency and severity of headaches, which were common in the study populations.
Study Objectives, Specific Aims, and Hypotheses: The objective of this study is to evaluate the efficacy of prazosin as a prophylactic treatment for persistent PTHAs, which will be accomplished by conducting a randomized placebo-controlled double blind trial of prazosin vs. placebo in active-duty SMs and Veterans who were in military service at any time from October 7, 2001 to the present with persistent PTHAs.
- Specific Aim 1: To determine the effect of prazosin compared to placebo on headache frequency, headache severity and duration, use of abortive/analgesic medications, and headache-related disability.
- Specific Aim 2: To determine the effect of prazosin on sleep disturbance, PTSD symptoms, depressive symptoms, alcohol consumption, global cognitive function, health-related quality of life, and global clinical status.
- Conditions
- Post-Traumatic Headache
- Being tested
- Prazosin, Placebo
- Keywords
- Chronic Headache, Post-Traumatic Stress Disorder, Iraq/Afghanistan Veteran
- Medical subject headings
- Post-Traumatic Headache, Headache Disorders, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrazosinDrug
Also called Minipress
PlaceboDrug
Also called inactive substance, sugar pill
| Study group | Role | What they receive |
|---|---|---|
| Prazosin | Experimental | Prazosin capsules beginning at 1 mg orally at bedtime. Titrate over 5 weeks to maximum dose of 5 mg in the morning and 20 mg at bedtime. Receives: Drug: Prazosin |
| Placebo | Placebo comparator | Placebo capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Headache Frequency
Headache log completed by participant to capture number of headaches experienced.
Measured: baseline, 4,8, and 12 weeks after steady dose
Secondary outcomes (2)
Overall Sleep Quality as Assessed by Pittsburgh Sleep Quality Index
Overall sleep quality assessed utilizing the Pittsburgh Sleep Quality Index (PSQI). The PSQI contains 19 self-rated questions. The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points. The seven component scores are then added to yield one "global" score with a range of 0-21 points, "0" indicating no difficulty and "21" indicating sever difficulty in all areas.
Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: TOTAL < 5 associated with good sleep quality. TOTAL > 5 associated with poor sleep quality The difference between means is shown for weeks 4, 8 and 12.
Measured: baseline, 4, 8, 12 weeks after steady dose
Insomnia Severity Index
Insomnia severity assessed using the Insomnia Severity Index (ISI). This 7-item self-report is designed to measure and detect cases of insomnia. Each question is scored on a scale of 0 to 4. The 7 items are added together.
Sum scores for items 1-7 0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate severity) 22-28 = Clinical insomnia (severe) The difference between means is shown for weeks 4, 8 and 12.
Measured: baseline, 4, 8, 12 weeks after steady dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2016 (estimated)
- Study start29 Nov 2016
- Primary completion9 May 2023
- Study completion7 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Post-Traumatic HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Institute for Biomedical and Clinical Research
- Sponsor type
- University, hospital or other
- Collaborators
- VA Puget Sound Health Care System, Madigan Army Medical Center
- Responsible party
- Sponsor
- Investigators
- Murray A Raskind, MD, Principal investigator, VA Puget Sound Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02965027
- Sponsor's protocol ID
- W81XWH-15-2-0060
- Status last verified
- Jun 2024
- First submitted
- 14 Nov 2016
- Last updated
- 10 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prazosin for the Prophylaxis of Chronic Post-Traumatic Headaches in OEF/OIF/OND Service Members and Veterans With Mild TBI
- ClinicalTrials.gov ID
- NCT02965027
- Acronym / sponsor ID
- W81XWH-15-2-0060
- Conditions
- Post-Traumatic Headache
- Keywords
- Chronic Headache, Post-Traumatic Stress Disorder, Iraq/Afghanistan Veteran
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Seattle Institute for Biomedical and Clinical ResearchUniversity, hospital or other
- Collaborators
- VA Puget Sound Health Care System, Madigan Army Medical Center
- Study start
- 29 Nov 2016 (actual)
- Primary completion
- 9 May 2023 (actual)
- Study completion
- 7 Jun 2023 (actual)
- First posted
- 16 Nov 2016 (estimated)
- Results
- Posted 10 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mild traumatic brain injury (mTBI) caused by blast effects of explosive devices has been called the "signature injury" of soldiers who served in the Iraq and Afghanistan conflicts. mTBI can also occur from impact or hitting the head on an object or the ground. Although termed "mild" in comparison to major brain injuries, people with mTBI can have problems with their memory and concentration. People with mTBI can also find they are more irritable, have more anxiety, and have trouble with their mood and sleep.
The purpose of this study is to see if a medication called prazosin can help treat chronic headaches in people with mTBI. The Food and Drug Administration (FDA) has approved prazosin for treating people with high blood pressure. At this time, the FDA has not approved prazosin in the treatment of mTBI or headaches. Some people who have posttraumatic stress disorder (PTSD) and have been taking prazosin for their medical conditions or who have taken it in research studies have said they have fewer headaches.
Detailed description
Background and Rationale: Headaches following mild traumatic brain injury (mTBI) are common, can be refractory to standard therapies, and may persist and worsen to become a debilitating chronic pain syndrome. The purpose of this study is to evaluate the centrally acting alpha-1 adrenoreceptor (AR) antagonist drug prazosin as a prophylactic treatment for chronic posttraumatic headaches (PTHAs). The impetus for this study comes from a large open-label case series in Iraq and Afghanistan Veterans with mTBI and PTHAs and data from a placebo-controlled trial evaluating use of prazosin for posttraumatic stress disorder (PTSD) in active-duty Servicemembers (SMs). Findings from these studies showed that in addition to decreasing PTSD-related symptoms and improving sleep quality, prazosin decreased the frequency and severity of headaches, which were common in the study populations.
Study Objectives, Specific Aims, and Hypotheses: The objective of this study is to evaluate the efficacy of prazosin as a prophylactic treatment for persistent PTHAs, which will be accomplished by conducting a randomized placebo-controlled double blind trial of prazosin vs. placebo in active-duty SMs and Veterans who were in military service at any time from October 7, 2001 to the present with persistent PTHAs.
- Specific Aim 1: To determine the effect of prazosin compared to placebo on headache frequency, headache severity and duration, use of abortive/analgesic medications, and headache-related disability.
- Specific Aim 2: To determine the effect of prazosin on sleep disturbance, PTSD symptoms, depressive symptoms, alcohol consumption, global cognitive function, health-related quality of life, and global clinical status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prazosin | Experimental | Drug: PrazosinPrazosin capsules beginning at 1 mg orally at bedtime. Titrate over 5 weeks to maximum dose of 5 mg in the morning and 20 mg at bedtime. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female Active-duty Servicemembers (SMs) or Veterans aged 18 or older who are in good general health.
- History of blast and/or impact head trauma mild traumatic brain injury (mTBI) meeting Defense and Veterans Brain Injury Center (DVBIC) mTBI criteria.
- o Mild TBI is defined as an injury to the head causing at least one of the following: alteration in consciousness (for up to 24 hours after the injury), loss of consciousness (0-30 minutes), and/or post-traumatic amnesia (up to 1 day post-injury). If available, the Glasgow Coma Scale score must be 13-15, and head imaging findings (if imaging was performed) must be negative.
- Frequent headaches (HAs) that started within 3 months after a head injury or marked worsening (a two-fold or greater increase in frequency and/or severity) of pre-existing headaches within 3 months of head injury.
- Participants 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 clinician prescriber during the study. Participants who are not of childbearing potential are not required to use contraception during the study.
Key exclusion criteria (33 listed)
- Participation in other interventional research.
- History of penetrating head injury
- History of TBI more severe than mild by DVBIC criteria
- A primary non migraine and/or tension-type HA disorder (for example hemicrania continua; cluster) that accounts for the majority of current symptoms.
- HAs of any kind of moderate or severe intensity on an average of more than 4 days per month preceding the concussive trauma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrazosinAlso: Minipress | Drug | Prazosin |
| PlaceboAlso: inactive substance, sugar pill | Drug | Placebo |
Primary outcome
Change From Baseline in Headache Frequency
Time frame: baseline, 4,8, and 12 weeks after steady dose
Headache log completed by participant to capture number of headaches experienced.
2 secondary outcomes
Overall Sleep Quality as Assessed by Pittsburgh Sleep Quality Index
Time frame: baseline, 4, 8, 12 weeks after steady dose
Insomnia Severity Index
Time frame: baseline, 4, 8, 12 weeks after steady dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Murray A Raskind, MD principal investigator
VA Puget Sound Health Care System
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prazosin in people with Post-Traumatic Headache, run by Seattle Institute for Biomedical and Clinical Research at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Headache Frequency (time frame: baseline, 4,8, and 12 weeks after steady dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024; AzTrials last refreshed its copy on 27 Oct 2026.