Trial Outcomes & Findings for Chronic Postconcussive Headache: A Placebo-Controlled Treatment Trial of Prazosin (NCT NCT02266329)

NCT ID: NCT02266329

Last Updated: 2024-06-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

89 participants

Primary outcome timeframe

Baseline to 12 weeks

Results posted on

2024-06-26

Participant Flow

166 participants completed the informed consent process, agreeing to participation. 77 of those participants failed the screening process, declined to participate prior to study drug randomization, or were lost to follow-up prior to study drug randomization. 89 participants were randomized to study drug.

Participant milestones

Participant milestones
Measure
Prazosin
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. prazosin hydrochloride: 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.
Placebo
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. placebo: Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.
Overall Study
STARTED
59
30
Overall Study
COMPLETED
52
26
Overall Study
NOT COMPLETED
7
4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Prazosin
n=59 Participants
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. prazosin hydrochloride: 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.
Placebo
n=30 Participants
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. placebo: Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.
Total
n=89 Participants
Total of all reporting groups
Age, Categorical
<=18 years
1 Participants
n=5 Participants
00 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
57 Participants
n=5 Participants
30 Participants
n=7 Participants
87 Participants
n=5 Participants
Age, Categorical
>=65 years
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Age, Continuous
38.6 years
STANDARD_DEVIATION 11.9 • n=5 Participants
37.6 years
STANDARD_DEVIATION 10.1 • n=7 Participants
38.3 years
STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
5 Participants
n=7 Participants
11 Participants
n=5 Participants
Sex: Female, Male
Male
53 Participants
n=5 Participants
25 Participants
n=7 Participants
78 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
11 Participants
n=5 Participants
5 Participants
n=7 Participants
16 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
34 Participants
n=5 Participants
20 Participants
n=7 Participants
54 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
14 Participants
n=5 Participants
5 Participants
n=7 Participants
19 Participants
n=5 Participants
Race/Ethnicity, Customized
American Indian or Alaskan Native
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Asian
2 Participants
n=5 Participants
1 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
12 Participants
n=5 Participants
8 Participants
n=7 Participants
20 Participants
n=5 Participants
Race/Ethnicity, Customized
White
31 Participants
n=5 Participants
18 Participants
n=7 Participants
49 Participants
n=5 Participants
Race/Ethnicity, Customized
Hawaiian Native or Pacific Islander
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Missing/Unknown
3 Participants
n=5 Participants
0 Participants
n=7 Participants
3 Participants
n=5 Participants
Race/Ethnicity, Customized
More than one race
5 Participants
n=5 Participants
0 Participants
n=7 Participants
5 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
2 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
Region of Enrollment
United States
59 Participants
n=5 Participants
30 Participants
n=7 Participants
89 Participants
n=5 Participants
Headache frequency
15.5 headaches
STANDARD_DEVIATION 6.1 • n=5 Participants
17.1 headaches
STANDARD_DEVIATION 6.0 • n=7 Participants
16.0 headaches
STANDARD_DEVIATION 6.1 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 12 weeks

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.

Outcome measures

Outcome measures
Measure
Prazosin
n=59 Participants
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. prazosin hydrochloride: 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.
Placebo
n=30 Participants
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. placebo: Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.
Headache Diary
-10.7 headaches per month
Standard Error 0.9
-6.9 headaches per month
Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) to Week 12 (i.e., following 12 weeks of drug treatment) in 4-week average peak HA severity, as determined from Headache Log data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) to Week 12 (i.e., following 12 weeks of drug treatment) in 4-week average total number of hours of HA pain of any severity, as determined from Headache Log data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) to Week 12 (i.e., following 12 weeks of drug treatment) in 4-week average frequency of use of abortive and/or analgesic HA treatment medications, as determined from Headache Log data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) in average headache-related disability, as measured 1) in 4-week treatment intervals using the Headache Impact Test-6 and 2) in the full 12-week treatment interval using the Migraine Disability Assessment (for subjects who meet diagnostic criteria for migraine).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) in PTSD symptom severity, as measured using the PTSD Checklist (PCL) given at baseline and at 4-week treatment intervals.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pretreatment) in sleep characteristics, including sleep quality, quantity, and efficiency using 1) the Pittsburgh Sleep Quality Index and the Insomnia Severity Index given at baseline and at 4-week treatment intervals and 2) sleep diary and wrist actigraphy performed for one week at baseline and after 11 weeks of treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) in concussion-related symptoms, as measured at 4-week treatment intervals using the Neurobehavioral Symptom Inventory

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) in depressive symptoms, as measured at 4-week treatment intervals using the Patient Health Questionnaire-9.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) in alcohol use, as measured at 4-week treatment intervals using the Alcohol Use Disorders Identification Test-Consumption.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) in cognitive function, as measured at 4-week treatment intervals using the Montreal Cognitive Assessment (MoCA).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) to Week 12 (i.e., following 12 weeks of drug treatment) in pupillary light responses using pupillometry, as a measure of sympathetic activation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Change from baseline (pre-treatment) to Week 12 (i.e., following 12 weeks of drug treatment) in light sensitivity symptoms, as determined using a modified Utah Photophobia Symptom Impact Scale - 12-Item)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to 12 weeks

Number of patients with a 50% or more decrease in mean number of headache days per 4 weeks, as determined at 4 week treatment intervals using Headache Log data.

Outcome measures

Outcome data not reported

Adverse Events

Prazosin

Serious events: 1 serious events
Other events: 52 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Prazosin
n=59 participants at risk
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. prazosin hydrochloride: 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.
Placebo
n=30 participants at risk
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. placebo: Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.
Surgical and medical procedures
Planned surgical procedure
1.7%
1/59 • Number of events 1 • 24 weeks
3.3%
1/30 • Number of events 1 • 24 weeks

Other adverse events

Other adverse events
Measure
Prazosin
n=59 participants at risk
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. prazosin hydrochloride: 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.
Placebo
n=30 participants at risk
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. placebo: Oral capsules of placebo identical in appearance to prazosin capsules titrated in the same manner as prazosin.
Cardiac disorders
Palpitations
35.6%
21/59 • Number of events 23 • 24 weeks
20.0%
6/30 • Number of events 6 • 24 weeks
Gastrointestinal disorders
Nausea
33.9%
20/59 • Number of events 25 • 24 weeks
13.3%
4/30 • Number of events 4 • 24 weeks
General disorders
Dizziness (any)
62.7%
37/59 • Number of events 51 • 24 weeks
20.0%
6/30 • Number of events 7 • 24 weeks
General disorders
Dizziness on Standing
40.7%
24/59 • Number of events 30 • 24 weeks
3.3%
1/30 • Number of events 1 • 24 weeks
General disorders
Drowsiness/Lethargy
44.1%
26/59 • Number of events 30 • 24 weeks
16.7%
5/30 • Number of events 5 • 24 weeks
General disorders
Insomnia
13.6%
8/59 • Number of events 10 • 24 weeks
6.7%
2/30 • Number of events 2 • 24 weeks
General disorders
Lightheadedness
47.5%
28/59 • Number of events 32 • 24 weeks
36.7%
11/30 • Number of events 11 • 24 weeks
General disorders
Low Energy
27.1%
16/59 • Number of events 17 • 24 weeks
10.0%
3/30 • Number of events 3 • 24 weeks
General disorders
Nasal Congestion
32.2%
19/59 • Number of events 21 • 24 weeks
10.0%
3/30 • Number of events 3 • 24 weeks
General disorders
Peripheral Edemna
18.6%
11/59 • Number of events 12 • 24 weeks
10.0%
3/30 • Number of events 4 • 24 weeks
General disorders
Vertigo
1.7%
1/59 • Number of events 1 • 24 weeks
3.3%
1/30 • Number of events 1 • 24 weeks
General disorders
Weakness (generalized)
10.2%
6/59 • Number of events 6 • 24 weeks
3.3%
1/30 • Number of events 1 • 24 weeks
General disorders
Headache worsening
3.4%
2/59 • Number of events 2 • 24 weeks
13.3%
4/30 • Number of events 5 • 24 weeks
Psychiatric disorders
Depression or depressed mood
11.9%
7/59 • Number of events 7 • 24 weeks
6.7%
2/30 • Number of events 2 • 24 weeks
Psychiatric disorders
Suicidal Ideation
5.1%
3/59 • Number of events 3 • 24 weeks
0.00%
0/30 • 24 weeks
Renal and urinary disorders
Incontinence
6.8%
4/59 • Number of events 4 • 24 weeks
0.00%
0/30 • 24 weeks

Additional Information

Hollie Holmes

VA Puget Sound Health Care System

Phone: 206-277-6207

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place