Effectiveness of Propranolol For Treating People With Post-Traumatic Stress Disorder

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00648375
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 69
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the effectiveness of propranolol in reducing symptoms of distress in people with post-traumatic stress disorder.

Condition or Disease	Intervention/Treatment	Phase
Post-Traumatic Stress Disorder	Drug: Propanolol; Drug: Placebo; Behavioral: Cognitive therapy workbook	Phase 4

Detailed Description

Post-traumatic stress disorder (PTSD) is a common and disabling condition, with about 10% of people having experienced PTSD at some point during their lives. The diagnosis of PTSD requires certain criteria: exposure to a severe psychological trauma and the persistent presence of three symptom clusters that include re-experiencing the traumatic event, physiologic hyperarousal, and emotional numbing paired with avoidance of stimuli associated with the event. Stimuli and cues associated with the trauma, such as features of an assailant or accident site, can cause a person to re-experience the traumatic memory and associated feelings of helplessness and fear. When re-experiencing a traumatic memory, people with PTSD usually undergo a heightened stress-related hormonal response that further solidifies new stimulating associations with the traumatic memory. Treatment with propranolol, a blood pressure-lowering drug that reduces stress-related hormonal responses, may be an effective means of preventing the formation of traumatic memories and of improving PTSD symptoms. This study will evaluate the effectiveness of propranolol in reducing symptoms of distress associated with traumatic memories in people with PTSD.

Participation in this study will last 14 weeks. All potential participants will undergo a 4-hour initial visit that will begin with a medical and psychiatric history review, a psychiatric interview, and symptom questionnaires. Participants will then be assigned randomly to take a test dose of either propranolol or placebo. Upon completion of the test dose, participants will begin 14 weeks of treatment with their assigned test dose medication. Participants will be asked to take the study medication each time they have a traumatic memory associated with hyperarousal symptoms, but no more than two times a day. Using a cognitive behavioral therapy based-workbook, participants will track their symptoms daily and when they use cognitive techniques to relieve symptoms.

Participants will attend study visits every 2 weeks for the 14 weeks of treatment. During these visits, participants will describe any side effects experienced, complete interviews and questionnaires about PTSD symptom severity, review with study officials their daily workbook entries, and pick up medication. Study participation will end upon completion of the Week 14 study visit.

For information on a related study, please follow this link:

http://clinicaltrials.gov/show/NCT00391430

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Propanolol for Treatment of Posttraumatic Stress Disorder
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Propranolol Participants will take propranolol for 14 weeks. Medication will be self-administered times they experience acute onset of hyperarousal symptoms, not more than twice per day.	Drug: Propanolol; Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours.; Other Names: Inderal ; Behavioral: Cognitive therapy workbook; Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Placebo Comparator: Placebo Participants will take placebo for 14 weeks. Medication will be self-administered times they experience acute onset of hyperarousal symptoms, not more than twice per day.	Drug: Placebo; Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours.; Behavioral: Cognitive therapy workbook; Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.

Outcome Measures

Primary Outcome Measures

1. Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX) [Measured at Week 0, 2,4,6,8,10,12,14]

   Scores range from 0-70, higher scores represent more severe symptoms

Secondary Outcome Measures

1. Change in Depression Measured by Beck Depression Inventory (BDI) [Measured at Weeks 0,2,4,6,8,10,12, 14]

   Scores range from 0-30, higher scores represent more severe symptoms

2. Change in Post-traumatic Scale-Self Score (PS-SR) [Measured at Weeks 0,2,4,6,8,10,12, 14]

   This is a 17-item self-report scale. Scores range from 0-51, higher scores represent more severe symptoms.

3. Change in Brief Symptoms Inventory-Short Form (BSI-SF) [Measured at Weeks 0,2,4,6,8,10,12, 14]

   BSI-SF is an 18 item scale used for a global score of general distress. Scores range from 0-72, higher scores represent more severe symptoms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• DSM-IV diagnosis of PTSD or meets the five of the six diagnostic criteria for PTSD (event, hyperarousal, re-experiencing, duration, and distress/impaired functioning symptom criteria), but not the avoidance/numbing symptom criteria

Exclusion Criteria:

• Past or current asthma

• Diabetes or heart disease

• Currently pregnant or breastfeeding

• Concurrent use of daily benzodiazepine; daily use of antidepressant medication allowed if dose has been stable for the 3 months before study entry

• Exposure therapy or additional cognitive therapy during the course of the study (supportive psychotherapy is allowed if ongoing for at least 3 months before study entry)

• Substance abuse

• Current use of beta blockers, amiodarone, chlorpromazine, cimetidine, clonidine, or digoxin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical College	New York	New York	United States	10065

Sponsors and Collaborators

• Weill Medical College of Cornell University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Margaret Altemus, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00648375
• Other Study ID Numbers: P50MH058911-01; P50MH058911-01; 0305006139
• First Posted: Apr 1, 2008
• Last Update Posted: Jan 2, 2020
• Last Verified: Dec 1, 2019

• Keywords provided by Weill Medical College of Cornell University: Propanolol; Beta Blockers; Reconsolidation; Cognitive Therapy; PTSD
• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Propranolol

Study Results

Participant Flow

Pre-assignment Detail	12 subjects were screened for the study. 3 subjects met enrollment criteria and were randomized to study medication.

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Period Title: Overall Study
STARTED	1	2
COMPLETED	1	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Propranolol	Placebo	Total
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Total of all reporting groups
Overall Participants	1	2	3
Age (years) [Mean (Full Range) ]
age	42	36.5	38.3
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	2 100%	3 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 100%	2 100%	3 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	1 100%	2 100%	3 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	2 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	Change in Severity of PTSD Symptoms Measured by Clinician Administered PTSD Scale for DSM-IV (CAPS-DX)
Description	Scores range from 0-70, higher scores represent more severe symptoms
Time Frame	Measured at Week 0, 2,4,6,8,10,12,14

Outcome Measure Data

Analysis Population Description

3 subjects enrolled in the study and completed all study visits.

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Measure Participants	1	2
Baseline	58	59
Week 2	62	60
Week 4	56	49.5
Week 6	45	44
Week 8	40	45.5
Week 10	32	35
Week 12	29	35
Week 14	27	28

2. Secondary Outcome

Title	Change in Depression Measured by Beck Depression Inventory (BDI)
Description	Scores range from 0-30, higher scores represent more severe symptoms
Time Frame	Measured at Weeks 0,2,4,6,8,10,12, 14

Outcome Measure Data

Analysis Population Description

3 subjects were enrolled and randomized: one to active propranolol and two to placebo. Total number of subjects was too low to perform statistical analysis

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Measure Participants	1	2
Baseline	12	13
Week 2	11	13
Week 4	12	9.5
Week 6	9	9.5
Week 8	9	10
Week 10	7	7.5
Week 12	7	8.5
Week 14	6	7

3. Secondary Outcome

Title	Change in Post-traumatic Scale-Self Score (PS-SR)
Description	This is a 17-item self-report scale. Scores range from 0-51, higher scores represent more severe symptoms.
Time Frame	Measured at Weeks 0,2,4,6,8,10,12, 14

Outcome Measure Data

Analysis Population Description

3 subject were enrolled: 1 was randomized to propranolol and 2 were randomized to placebo.

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Measure Participants	1	2
Baseline	36	42.5
Week 2	38	42.5
Week 4	38	36.5
Week 6	30	35.5
Week 8	28	32
Week 10	18	26.5
Week 12	19	24
Week 14	17	20.5

4. Secondary Outcome

Title	Change in Brief Symptoms Inventory-Short Form (BSI-SF)
Description	BSI-SF is an 18 item scale used for a global score of general distress. Scores range from 0-72, higher scores represent more severe symptoms
Time Frame	Measured at Weeks 0,2,4,6,8,10,12, 14

Outcome Measure Data

Analysis Population Description

3 subjects were randomized, one to propranolol and one to placebo. The total number of subjects was too low to perform statistical analysis.

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.	Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
Measure Participants	1	2
Baseline	28	41
Week 2	34	42
Week 4	30	35
Week 6	28	31
Week 8	32	32
Week 10	26	25
Week 12	23	24.5
Week 14	18	20

Adverse Events

Time Frame	14 weeks
Arm/Group Title	Propranolol		Placebo
Arm/Group Description	Participants will take propranolol for 14 weeks. Propanolol: Participants will take a 40-mg dose of propranolol immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.		Participants will take placebo for 14 weeks. Placebo: Participants will take a single dose of placebo immediately after they experience a traumatic memory associated with strong hyperarousal symptoms. Participants may take up to two doses a day, if the doses are separated by at least 6 hours. Cognitive therapy workbook: Participants will also receive a cognitive behavioral therapy-based workbook in which they will track symptoms and efforts to use cognitive techniques to relieve symptoms each day.
All Cause Mortality
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Serious Adverse Events
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)

Limitations/Caveats

Due to small numbers of subjects in both arms, statistical analyses were not possible.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.