Chronic Postconcussive Headache: A Placebo-Controlled Treatment Trial of Prazosin

NCT02266329 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: N1136-W1IK2RX001136-01A2
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if prazosin is more effective than placebo in decreasing frequency, severity, disability, and other negative effects of headaches related to mild traumatic brain injury in Service Members and Veterans.

Conditions

Posttraumatic Headache; Combat Disorders; Post Concussion Syndrome; Headache; Mild Traumatic Brain Injury; Posttraumatic Migraine

Keywords

controlled clinical trial; randomized controlled clinical trial

Outcome Measures

Primary Outcomes (1)

• Headache Diary

  Change from baseline (pre-treatment) to Week 12 (i.e., following 12 weeks of drug treatment) of either 1) Headaches that last 4 or more hours a day and reach a moderate to severe intensity at any point or 2) Headaches of any intensity if a medication or other treatment is used in an effort to stop the Headaches, as determined from Headache Log data.

  Baseline to 12 weeks

Secondary Outcomes (9)

• Headache Impact Test-6 (HIT-6)

  Baseline to 12 weeks

• PTSD Checklist for DSM-5 (PCL-5)

  Baseline to 12 weeks

• Pittsburgh Sleep Quality Index (PSQI)

  Baseline to 12 weeks

• Neurobehavioral Symptom Inventory (NSI)

  Baseline to 12 weeks

• Patient Health Questionnaire-9 (PHQ-9)

  Baseline to 12 weeks

Other Outcomes (4)

• Change From Baseline in Pupillary Light Responses

  Baseline to 12 Weeks

• Change From Baseline in Frequency of Use of Abortive/Analgesic Agents

  Baseline to Week 12

• Change From Baseline in 4-week Average Total Number of Hours of HA Pain

  Baseline to Week 12

Study Arms (2)

prazosin

ACTIVE COMPARATOR

Subjects will be gradually titrated up to the maximum dose or the maximum tolerated dose based on a dosing algorithm. The maximum dose to be used in this trial is 5mg in the morning and 20 mg at bedtime.

Drug: prazosin hydrochloride

placebo

PLACEBO COMPARATOR

Subjects will be gradually titrated up to the maximum dose or the maximum tolerated dose based on a dosing algorithm. The maximum dose to be used in this trial is 5mg in the morning and 20 mg at bedtime.

Drug: placebo

Interventions

prazosin hydrochloride DRUG

Prazosin as oral capsules titrated to the maximum dose or the maximum tolerated dose based on a dosing algorithm. The maximum dose to be used in this trial is 5mg in the morning and 20 mg at bedtime.

Also known as: Minipress

prazosin

placebo DRUG

Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.

Also known as: inactive drug; sugar pill; dummy pill

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veterans or active duty service members aged 18 or older of either gender
• Good general health
• History of blast and/or impact head/neck trauma meeting DVBIC criteria for mild TBI, i.e., injury as manifested by at least one of the following:
• \) any period of loss of consciousness
• \) any loss of memory for events immediately before or after the accident
• \) any alteration in mental status at the time of the accident (e.g., feeling dazed, disoriented, or confused)
• \) focal neurological deficit(s) that may or may not be transient, with severity of injury not exceeding loss of consciousness 30 minutes, Glasgow Coma Scale \<13-15 after 30 minutes, or posttraumatic amnesia \>24 hrs,
• Headaches that started within 3 months of a head/neck injury or pre-existing headaches that markedly worsened (by a two-fold or greater increase in frequency and/or severity) within 3 months of a head/neck injury. Headaches must either 1) 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 uses a medication or other agent in an effort to stop the headache. Headaches meeting these criteria must have been present on average at least 8 days per 4-week period over the 3 months preceding study enrollment.
• Fluency in English is required.
• Persons of all races and ethnicities are eligible.
• Female participants must agree to abstain from sexual relations that could result in pregnancy or use a reliable form of birth control during the study.
• Continued use of prophylactic migraine medication other than the study drug is permissible if the participant has been on a stable dose for at least 4 weeks prior to the preliminary screening period and intends to continue the medication for the duration of the trial.

You may not qualify if:

• Participation in other interventional research.
• History of TBI more severe than that classified as mild by DVBIC criteria
• A primary non migraine and/or tension-type headache disorder that accounts for the majority of current symptoms
• History of penetrating head injury
• Headaches of any kind of moderate or severe intensity on an average of more than 4 days per month preceding the concussive trauma
• Current substance use disorder per DSM-V criteria except caffeine- or tobacco-related disorders.
• Structural brain abnormalities on any prior imaging with associated clinically evident manifestations.
• Current participation in transcranial magnetic stimulation studies.
• Unable to reliably keep the headache log on a minimum of 80% of recordable days
• Women of childbearing potential must not be pregnant, planning to become pregnant during the study period, or nursing.
• Participation in a headache support group or other activity such as meditation or yoga intended to mitigate headache or other chronic pain must be stable for at least 4 weeks prior to beginning the preliminary screening period and should be intended to be continued for the duration of the trial. Participants will be encouraged to defer enrolling in such activities until they have completed the treatment trial.
• Current use of prazosin at a dose of 4 mg or less is not excluded, however requires a 2-week wash-out period prior to beginning the baseline headache log-keeping period.
• Allergy or previous adverse reaction to prazosin or other alpha-1 antagonist
• Subjects must be on a stable dose of the following medications/treatments for at least 4 weeks prior to the preliminary screening period, and must intend to continue the medication for the duration of the trial: psychoactive drugs, for example anticonvulsants, benzodiazepines, antidepressants, sedative/hypnotics; antihypertensive medications, including beta blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers; magnesium prescribed specifically for headache.
• Potential participants who have been taking trazodone will undergo a 2-week washout period before beginning the preliminary screening period. Because combining prazosin and trazodone may increase risk of priapism, trazodone is not allowed during the study.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

Location

MeSH Terms

Conditions

Post-Traumatic Headache; Combat Disorders; Post-Concussion Syndrome; Headache; Brain Concussion

Interventions

Prazosin

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Wounds, Nonpenetrating; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Injuries, Traumatic; Brain Injuries

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Change from baseline in headache (HA) frequency (1. Primary Outcome Measure) is based on linear mixed effects regression of outcome on study visit by treatment interaction with study participant as a random effect.

Results Point of Contact

• Title: Hollie Holmes
• Organization: VA Puget Sound Health Care System

Hollie.Holmes@va.gov

206-277-6207

Study Officials

• Cynthia L Mayer, DO

  VA Puget Sound Health Care System Seattle Division, Seattle, WA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized double blind placebo-controlled clinical trial with 2:1 chance of randomization to active drug.

Study Record Dates

• First Submitted: October 10, 2014
• First Posted: October 17, 2014
• Study Start: January 4, 2016
• Primary Completion: May 31, 2023
• Study Completion: September 30, 2023
• Last Updated: March 30, 2026
• Results First Posted: June 26, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)