Clinical trial NCT02266329
Conditions: Posttraumatic Headache Combat Disorders Post Concussion Syndrome Headache Mild Traumatic Brain Injury Posttraumatic Migraine
Keywords: controlled clinical trial randomized controlled clinical trial
Sponsor: VA Office of Research and Development
Start date: 2016-01-04; Completion date: 2023-09-30
Enrollment: 89 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Detailed description:
Headaches following combat-related post-concussive injury are common, and in some patients can increase in frequency and severity to become very debilitating. Posttraumatic headaches (PTHAs), particularly those following blast-related head injury, can be resistant to standard headache therapies. The objective of this study is to evaluate the effectiveness of the medication prazosin as a prophylactic (preventive) agent in treating combat-related PTHAs. Prazosin is a generic drug originally marketed over 30 years ago as a treatment for high blood pressure. It has subsequently been found to be safe and effective for treating other problems, including most recently posttraumatic stress disorder (PTSD) and disrupted sleep in active duty Iraq/Afghanistan Service Members and Veterans. In preliminary studies, prazosin has also been found to substantially reduce the intensity and frequency of PTHAs in this population. This finding is the motivation behind this study.

The investigators' hypotheses are (1) that prazosin will be more effective than placebo in easing the effects of chronic PTHAs, including headache frequency, duration, severity, use of abortive/analgesic medications, and disability caused, and (2) that improvement in headache parameters will be associated with improvement in sleep quality, PTSD symptom severity, mood, cognition, health-related quality of life, and global clinical status, and with moderation of alcohol consumption.

The total trial length is 22 - 24 weeks. Following an initial clinic visit to determine preliminary study eligibility, there will be a 4-week pre-treatment preliminary screening period, during which participants will keep a daily headache diary. The purpose of this is to confirm eligibility for randomization per inclusion/exclusion criteria and to collect baseline data for headache-related outcome measures. Participants confirmed to be eligible to continue in the study will then have a one-week sleep evaluation including actigraphy and keeping a daily sleep diary. This will be followed by a baseline study visit, during which baseline data for secondary outcome measures will be collected using validated structured self-reports and clinician interviews. Participants will be randomized 2:1 to prazosin or placebo, and the study drug dose will be gradually titrated over a 5 to 7-week period to 5 mg in the morning and 20 mg in the evening or the maximum tolerated dose. The dose titration will be followed by 12 weeks at steady-dose. For the last week of the steady-dose phase, participants will repeat the sleep evaluation. Participants will keep a headache log through the duration of the study. Results will be analyzed using standard statistical techniques.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: prazosin hydrochloride intervention 2: placebo
Intervention descriptions: intervention 1: 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. intervention 2: Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.

Protocol documents:
Prot_SAP_000.pdf: 
Chronic Postconcussive Headache: A Placebo-
Controlled Treatment Trial of Prazosin 
NCT02266329 
Approved November 12, 2021