Posttraumatic Stress DisordersPhase 4NCT00645450
PTSD Symptom Reduction by Propranolol Given After Trauma Memory Activation
A Phase 4 study testing Propranolol in people with Posttraumatic Stress Disorders, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This study is a randomized, double-blind, placebo-controlled clinical trial of propranolol combined with trauma memory reactivation, to determination if this approach is effective in treating PTSD symptoms. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Posttraumatic Stress Disorders
- What is being tested?
- Propranolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Dec 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- OEF/OIF veteran diagnosed with combat related posttraumatic stress disorder
Who cannot join
- Not diagnosed with current, chronic PTSD
- Current PTSD related to a traumatic event other than the event being treated
- Age>65.
- Systolic blood pressure <100 mm HG or resting HR less than 60 BPM.
- Medical condition that contraindicates the administration of propranolol, e.g. history of congestive heart failure, heart block, insulin-requiring diabetes, chronic bronchitis, emphysema, or asthma. With regard to asthma, because many persons who say they have had an asthma attack, especially as a child, may only have had hay fever, another allergy, or another non-asthmatic episode, a blanket exclusion criteria may be overly restrictive. Therefore asthma attacks will only be exclusionary if they a) occurred within the past 10 years, b) occurred at any time in life if induced by a beta-blocker, or c) are currently being treated, regardless of the date of last occurrence. Cardiological consultation will be obtained as necessary;
- Previous adverse reaction to, or non-compliance with a beta-blocker.
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- Current use of medication that may involve potentially dangerous interactions with propranolol, including, other beta-blockers, antiarrhythmics, calcium channel blockers, and potent P450 2D6 inhibitors, e.g., fluoxetine, paroxetine, micnazole, sulconazole, metaclopramide, quinidine, ticlopidine, and ritnavir.
- Presence of drugs of abuse, viz., opiates, marijuana, cocaine, or amphetamines, as determined by urine testing.
- Pregnancy (in women of child- bearing potential, a pregnancy test will be performed) or breast feeding.
- Contraindicating psychiatric condition, e.g., current psychotic, bipolar, melancholic, or substance dependence or abuse disorder.
- Initiation of, or change in, psychotropic medication within the previous two months. For subjects receiving stable doses of pharmacotherapy, they and their providers will be asked not to change the regimen except in clinically urgent circumstances. If this becomes necessary, a decision will be made on a case-by-case basis whether to retain the subject in the study or terminate participation.
- Current participation in any psychotherapy (other than supportive). Subjects will be asked not to initiate psychotherapy during the course of the proposed study except in clinically urgent circumstances; if this becomes necessary, a decision will be made on a case-by-case basis whether to retain the subject in the study or terminate participation.
- Inability to understand the study's procedures, risks, and side effects, or to otherwise give informed consent for participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Medical Center, Manchester
Manchester, New Hampshire, 03104
About this study
Official title: PTSD Symptom Reduction by Propranolol Given After Memory Activation
This study is a randomized, double-blind, placebo-controlled clinical trial of propranolol combined with trauma memory reactivation, to determination if this approach is effective in treating PTSD symptoms. Participants will include male and female combat Veterans of the Afghanistan and Iraqi wars meeting DSM-IV criteria for chronic PTSD, recruited locally from the Manchester VAMC Mental Hygiene Clinic or through advertising. The presence of PTSD will be assessed using the CAPS. Participants will be randomly assigned to the propranolol or placebo drug condition. During each of six memory reactivation sessions, the participant will meet with a psychiatrist, who will ask the participant to spend ten minutes describing the event that caused their PTSD, and their reactions to it. The interviewer will facilitate this process by asking questions, keeping the participant focused on the traumatic event and encouraging him/her to identify aspects of the traumatic event that continue to provoke emotional distress. The traumatic memory reactivation will be immediately followed by administration of propranolol or placebo. Following the six treatment sessions, script-driven imagery will be used to assess HR, SC, and facial EMG responses to recollections of the traumatic event and PTSD symptoms will be assessed using the CAPS. A previously developed discriminant function will be used to classify each person as a physiologic "responder" or "non-responder." There will also be a 6-month follow-up assessment.
Read the detailed description
OBJECTIVE: In the first of two preliminary studies, the investigators demonstrated in individuals with chronic PTSD that a single (combined 40 mg short- and 60 mg long-acting) 24-hour oral dose of propranolol, compared to placebo, given immediately following reactivation of the PTSD-related memory of the traumatic event, significantly reduced physiological responses during script-driven imagery of that event measured one week later. These results support blockade of reconsolidation of the traumatic memory, a process that is entirely distinct from extinction. In addition, the investigators found a trend for post-reactivation propranolol to reduce self-reported PTSD symptoms, measured via the Impact of Event Scale-Revised (IES-R). In the second preliminary study, the investigators performed 6 weekly treatments that consisted of the subject describing their PTSD-related traumatic events for approximately 10 minutes followed by 0.67 mg/kg (minimum 40 mg) short-acting propranolol plus 1 mg/kg (minimum 60 mg) long-acting propranolol. The mean Clinician Administered PTSD Scale (CAPS) Total Score following the six treatment sessions was reduced by 44% (p=.02). The proposed work will examine whether repeated treatments may succeed in producing more substantive symptomatic improvement.
RESEARCH PLAN: The study design will be a randomized, double-blind, placebo-controlled, clinical trial. A crossover design is not being proposed because the effect is expected to be neither short-term nor reversible. Rather, at the conclusion of the formal study period, individuals randomized to the placebo condition will be offered an equal number of treatment sessions with propranolol. A placebo control will be used, rather than an active treatment control, because the proposed study will be a "proof of concept" test of post-reactivation pharmacological reduction of traumatic memories. The control (and active) treatments will be structured so as to minimize the chance of extinction. The investigators recognize that eventually this new treatment will need to be tested against established PTSD treatments, including exposure, if its clinical utility is to be established. The investigators regard this as a matter for subsequent studies should the present study yield promising results. However, the investigators do intend to compare the effect size the investigators find for the proposed intervention with published effect sizes for other PTSD psychotherapies.
METHODOLOGY: Participants will include male and female combat Veterans of the Afghanistan and Iraqi wars meeting DSM-IV criteria for chronic PTSD, recruited locally from the Manchester VAMC Mental Hygiene Clinic or through advertising. The presence of PTSD will be assessed using the CAPS. Participants will be randomly assigned to the propranolol or placebo drug condition. During each of six memory reactivation sessions, the participant will meet with a psychiatrist, who will ask the participant to spend ten minutes describing the event that caused their PTSD, and their reactions to it. The interviewer will facilitate this process by asking questions, keeping the participant focused on the traumatic event and encouraging him/her to identify aspects of the traumatic event that continue to provoke emotional distress. The traumatic memory reactivation will be immediately followed by administration of propranolol or placebo. Following the six treatment sessions, script-driven imagery will be used to assess HR, SC, and facial EMG responses to recollections of the traumatic event and PTSD symptoms will be assessed using the CAPS. A previously developed discriminant function will be used to classify each person as a physiologic "responder" or "non-responder." There will also be a 6-month follow-up assessment.
CLINICAL RELEVANCE: The mechanism of memory reconsolidation offers the possibility that cellular plasticity can be capitalized on to reverse the neuroanatomical and neurophysiological underpinnings of traumatic memories. The possibility that a traumatic memory could be significantly weakened by an intervention as simple as the post-reactivation administration of a widely used and safe medication has profound implications for the treatment of PTSD.
- Conditions
- Posttraumatic Stress Disorders
- Being tested
- Propranolol, Placebo
- Keywords
- Stress, Posttraumatic, PTSD, Propranolol, Treatment
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropranololDrug
Also called Inderal, Inderal LA, Hemangeol, Inderal XL
Weekly doses of short and long acting propranolol (Inderal, Inderal LA, Hemangeol, Inderal XL) following recollection of traumatic memory
PlaceboDrug
Also called Inactive pill
Weekly doses of placebo (inactive pill) following recollection of traumatic memory
| Study group | Role | What they receive |
|---|---|---|
| Propranolol | Experimental | Weekly doses of short and long acting propranolol following recollection of traumatic memory Receives: Drug: Propranolol |
| Placebo | Placebo comparator | Weekly doses of placebo following recollection of traumatic memory Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PTSD Symptom Severity as Measured by Clinician-Administered PTSD Scale (CAPS)
CAPS scale measures intensity and frequency of each symptom separately on a 5 point Likert scale ranging from zero to four. The total CAPS symptom severity score ranges from 0-136, with higher scores indicating greater PTSD symptoms severity
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2008 (estimated)
- Study startApr 2008
- Primary completionJul 2010
- Study completionDec 2010
Why it stopped: Difficulty recruiting subjects and loss of study physician for new job
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Posttraumatic Stress DisordersStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Scott P Orr, PhD, Principal investigator, VA Medical Center, Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00645450
- Sponsor's protocol ID
- MHBA-013-07S
- Status last verified
- Jun 2019
- First submitted
- 19 Mar 2008
- Last updated
- 2 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Study terminated early.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PTSD Symptom Reduction by Propranolol Given After Memory Activation
- ClinicalTrials.gov ID
- NCT00645450
- Acronym / sponsor ID
- MHBA-013-07S
- Conditions
- Posttraumatic Stress Disorders
- Keywords
- Stress, Posttraumatic, PTSD, Propranolol, Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty recruiting subjects and loss of study physician for new job
- Enrolment
- 9 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Apr 2008 (actual)
- Primary completion
- Jul 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 27 Mar 2008 (estimated)
- Results
- Posted 2 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a randomized, double-blind, placebo-controlled clinical trial of propranolol combined with trauma memory reactivation, to determination if this approach is effective in treating PTSD symptoms. Participants will include male and female combat Veterans of the Afghanistan and Iraqi wars meeting DSM-IV criteria for chronic PTSD, recruited locally from the Manchester VAMC Mental Hygiene Clinic or through advertising. The presence of PTSD will be assessed using the CAPS. Participants will be randomly assigned to the propranolol or placebo drug condition. During each of six memory reactivation sessions, the participant will meet with a psychiatrist, who will ask the participant to spend ten minutes describing the event that caused their PTSD, and their reactions to it. The interviewer will facilitate this process by asking questions, keeping the participant focused on the traumatic event and encouraging him/her to identify aspects of the traumatic event that continue to provoke emotional distress. The traumatic memory reactivation will be immediately followed by administration of propranolol or placebo. Following the six treatment sessions, script-driven imagery will be used to assess HR, SC, and facial EMG responses to recollections of the traumatic event and PTSD symptoms will be assessed using the CAPS. A previously developed discriminant function will be used to classify each person as a physiologic "responder" or "non-responder." There will also be a 6-month follow-up assessment.
Detailed description
OBJECTIVE: In the first of two preliminary studies, the investigators demonstrated in individuals with chronic PTSD that a single (combined 40 mg short- and 60 mg long-acting) 24-hour oral dose of propranolol, compared to placebo, given immediately following reactivation of the PTSD-related memory of the traumatic event, significantly reduced physiological responses during script-driven imagery of that event measured one week later. These results support blockade of reconsolidation of the traumatic memory, a process that is entirely distinct from extinction. In addition, the investigators found a trend for post-reactivation propranolol to reduce self-reported PTSD symptoms, measured via the Impact of Event Scale-Revised (IES-R). In the second preliminary study, the investigators performed 6 weekly treatments that consisted of the subject describing their PTSD-related traumatic events for approximately 10 minutes followed by 0.67 mg/kg (minimum 40 mg) short-acting propranolol plus 1 mg/kg (minimum 60 mg) long-acting propranolol. The mean Clinician Administered PTSD Scale (CAPS) Total Score following the six treatment sessions was reduced by 44% (p=.02). The proposed work will examine whether repeated treatments may succeed in producing more substantive symptomatic improvement.
RESEARCH PLAN: The study design will be a randomized, double-blind, placebo-controlled, clinical trial. A crossover design is not being proposed because the effect is expected to be neither short-term nor reversible. Rather, at the conclusion of the formal study period, individuals randomized to the placebo condition will be offered an equal number of treatment sessions with propranolol. A placebo control will be used, rather than an active treatment control, because the proposed study will be a "proof of concept" test of post-reactivation pharmacological reduction of traumatic memories. The control (and active) treatments will be structured so as to minimize the chance of extinction. The investigators recognize that eventually this new treatment will need to be tested against established PTSD treatments, including exposure, if its clinical utility is to be established. The investigators regard this as a matter for subsequent studies should the present study yield promising results. However, the investigators do intend to compare the effect size the investigators find for the proposed intervention with published effect sizes for other PTSD psychotherapies.
METHODOLOGY: Participants will include male and female combat Veterans of the Afghanistan and Iraqi wars meeting DSM-IV criteria for chronic PTSD, recruited locally from the Manchester VAMC Mental Hygiene Clinic or through advertising. The presence of PTSD will be assessed using the CAPS. Participants will be randomly assigned to the propranolol or placebo drug condition. During each of six memory reactivation sessions, the participant will meet with a psychiatrist, who will ask the participant to spend ten minutes describing the event that caused their PTSD, and their reactions to it. The interviewer will facilitate this process by asking questions, keeping the participant focused on the traumatic event and encouraging him/her to identify aspects of the traumatic event that continue to provoke emotional distress. The traumatic memory reactivation will be immediately followed by administration of propranolol or placebo. Following the six treatment sessions, script-driven imagery will be used to assess HR, SC, and facial EMG responses to recollections of the traumatic event and PTSD symptoms will be assessed using the CAPS. A previously developed discriminant function will be used to classify each person as a physiologic "responder" or "non-responder." There will also be a 6-month follow-up assessment.
CLINICAL RELEVANCE: The mechanism of memory reconsolidation offers the possibility that cellular plasticity can be capitalized on to reverse the neuroanatomical and neurophysiological underpinnings of traumatic memories. The possibility that a traumatic memory could be significantly weakened by an intervention as simple as the post-reactivation administration of a widely used and safe medication has profound implications for the treatment of PTSD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propranolol | Experimental | Drug: PropranololWeekly doses of short and long acting propranolol following recollection of traumatic memory |
| Placebo | Placebo comparator | Drug: PlaceboWeekly doses of placebo following recollection of traumatic memory |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- OEF/OIF veteran diagnosed with combat related posttraumatic stress disorder
Key exclusion criteria (13 listed)
- Not diagnosed with current, chronic PTSD
- Current PTSD related to a traumatic event other than the event being treated
- Age>65.
- Systolic blood pressure <100 mm HG or resting HR less than 60 BPM.
- Medical condition that contraindicates the administration of propranolol, e.g. history of congestive heart failure, heart block, insulin-requiring diabetes, chronic bronchitis, emphysema, or asthma. With regard to asthma, because many persons who say they have had an asthma attack, especially as a child, may only have had hay fever, another allergy, or another non-asthmatic episode, a blanket exclusion criteria may be overly restrictive. Therefore asthma attacks will only be exclusionary if they a) occurred within the past 10 years, b) occurred at any time in life if induced by a beta-blocker, or c) are currently being treated, regardless of the date of last occurrence. Cardiological consultation will be obtained as necessary;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PropranololAlso: Inderal, Inderal LA, Hemangeol, Inderal XLWeekly doses of short and long acting propranolol (Inderal, Inderal LA, Hemangeol, Inderal XL) following recollection of traumatic memory | Drug | Propranolol |
| PlaceboAlso: Inactive pillWeekly doses of placebo (inactive pill) following recollection of traumatic memory | Drug | Placebo |
Primary outcome
PTSD Symptom Severity as Measured by Clinician-Administered PTSD Scale (CAPS)
Time frame: 3 years
CAPS scale measures intensity and frequency of each symptom separately on a 5 point Likert scale ranging from zero to four. The total CAPS symptom severity score ranges from 0-136, with higher scores indicating greater PTSD symptoms severity
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Study terminated early.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott P Orr, PhD principal investigator
VA Medical Center, Manchester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propranolol in people with Posttraumatic Stress Disorders, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PTSD Symptom Severity as Measured by Clinician-Administered PTSD Scale (CAPS) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2019.