Prazosin for Post-Concussive Headaches

NCT02965027 | Completed Phase 4 Results DMC

• 1 other identifier: W81XWH-15-2-0060
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Post-Traumatic Headache

Keywords

Chronic Headache; Post-Traumatic Stress Disorder; Iraq/Afghanistan Veteran

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Headache Frequency

  Headache log completed by participant to capture number of headaches experienced.

  baseline, 4,8, and 12 weeks after steady dose

Secondary Outcomes (2)

• Overall Sleep Quality as Assessed by Pittsburgh Sleep Quality Index

  baseline, 4, 8, 12 weeks after steady dose

• Insomnia Severity Index

  baseline, 4, 8, 12 weeks after steady dose

Study Arms (2)

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.

Drug: Prazosin

Placebo

PLACEBO COMPARATOR

Placebo capsules

Drug: Placebo

Interventions

Prazosin DRUG

Also known as: Minipress

Prazosin

Placebo DRUG

Also known as: inactive substance, sugar pill

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Seattle Institute for Biomedical and Clinical Research: lead
• VA Puget Sound Health Care System: collaborator
• Madigan Army Medical Center: collaborator

Study Sites (2)

VA Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98433, United States

Location

MeSH Terms

Conditions

Post-Traumatic Headache; Headache Disorders; Stress Disorders, Post-Traumatic

Interventions

Prazosin; Sugars

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

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

Hollie.Holmes@va.gov

206-277-6207

Study Officials

• Murray A Raskind, MD

  VA Puget Sound Health Care System

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2016
• First Posted: November 16, 2016
• Study Start: November 29, 2016
• Primary Completion: May 9, 2023
• Study Completion: June 7, 2023
• Last Updated: July 10, 2024
• Results First Posted: July 10, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)