Posttraumatic Stress DisorderNCT01449955
Rapamycin as a Means of Interference With Reconsolidation of Posttraumatic Stress Disorder-related Traumatic Memory
A study testing Rapamycin in people with Posttraumatic Stress Disorder, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The purpose of the proposed study is to determine if pairing reactivation of a traumatic memory with a single administration of Rapamycin (e.g., Sirolimus) in men with combat-related Posttraumatic Stress Disorder leads to a reduction of the emotional strength of that particular traumatic memory. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- Rapamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Jul 2010
- Phase
- Interventional
- 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 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male Veterans
- Diagnosis of Posttraumatic Stress Disorder related to combat
Who cannot join
- Hypersensitivity to Rapamycin
- Organic brain damage (including unresolved Traumatic Brain Injury sequela)
- Substance dependence in the last three months
- On any immunosuppressant therapy
- Prominent suicidal or homicidal features
- Medical conditions: systemic infections, congestive heart failure, renal failure, hepatic failure
Trial locations and contacts
1 site in 1 country.
United States1 site
VA North Texas Healthcare System
Dallas, Texas, 75216
About this study
Official title: mTOR Kinase as a Therapeutic Target in Reconsolidation of Posttraumatic Stress Disorder-related Traumatic Memory
The purpose of the proposed study is to determine if pairing reactivation of a traumatic memory with a single administration of Rapamycin (e.g., Sirolimus) in men with combat-related Posttraumatic Stress Disorder leads to a reduction of the emotional strength of that particular traumatic memory.
The following hypotheses will be tested:
- Traumatic memory reactivation paired with a single dose of Rapamycin will decrease objective measures of stress and self-report of stress during replay of the traumatic memory, relative to, subjects receiving placebo.
- Pairing administration of Rapamycin with traumatic memory reactivation will decrease symptoms of Posttraumatic Stress Disorder one month and three months later, relative to patients receiving placebo.
Read the detailed description
Post-traumatic stress disorder (PTSD) is characterized by intrusive memories in the form of unwanted images, nightmares, and flashbacks as the result of being exposed to a traumatic event . Current research efforts have begun to explore the underlying neurochemical changes associated with PTSD. Recently, these efforts have focused on the prevention of PTSD in persons exposed to trauma. For example, preliminary evidence suggests that interference with consolidation of trauma-related memories using the beta-antagonist, propranolol, may prevent PTSD in humans with recent traumas. However, given that as much as 90% of the US population is exposed to at least one traumatic event during their lifetimes, the utility of this treatment is limited by the logistical problems of treating everyone at risk. To date, there have been very few systematic studies on humans that focus on changing the underlying traumatic memory once PTSD has been established.
The trauma experience is initially stored in short-term memory, then consolidated into long-term memory. However, the long-term stability conferred by the consolidation process undergoes a period of labiality as follows. Each time a consolidated memory is activated, the memory trace becomes newly labile and must be consolidated again to remain in long-term memory5. This process is called reconsolidation. Reconsolidation therefore offers a biologic window during which long-term memories can be disrupted. Preclinical studies have begun to unravel the biological changes that underlie these processes. Both pharmacological agents, including glucocorticoids, and protein synthesis inhibitors can interfere with memory consolidation and reconsolidation. In preclinical studies, the global protein synthesis inhibitor anisomycin can block reconsolidation, leading to a reduction in strength of traumatic memories. Unfortunately, the toxicity of anisomycin is prohibitive for therapeutic use. Thus, rather than using a global protein synthesis inhibitor, a more effective and selective means of reducing consolidation of an established traumatic memory is to target only a subset of protein translation important for synaptic plasticity. The protein kinase mTOR (mammalian target of rapamycin) is just such a regulator of a subset of protein synthesis critical for synaptic plasticity.
- Conditions
- Posttraumatic Stress Disorder
- Being tested
- Rapamycin, Placebo
- Keywords
- PTSD
- 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.
RapamycinDrug
Also called Sirolimus, X-Rapamune
Sirolimus is an FDA approved immunosuppressant drug used to prevent rejection in organ transplantation, and is especially useful in kidney transplants. It is non-toxic to kidneys, unlike other immunosuppressants. In this study, the medication will be administered once to see if it interferes with emotional memory reconsolidation. This is based on the fact that it inhibits the mammalian target of Rapamycin (mTOR) through directly binding the mTOR Complex1 (mTORC1). mTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis and transcription.
a single dosage of 15mg will be administered during this study.
PlaceboDrug
Also called sugar pill
Inactive
| Study group | Role | What they receive |
|---|---|---|
| Placebo (e.g., sugar pill) | Placebo comparator | 15 mg Placebo will be administered once, in pill form. Receives: Drug: Placebo |
| Rapamycin | Active comparator | 15 mg of Rapamycin will be administered once, in pill form. Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
Clinician administered interview which assesses the symptoms of Posttraumatic Stress disorder at baseline, and then again 1 month posttreatment. The CAPS is a 25 item semi-structured interview that assesses the 17 DSM-IV PTSD criteria as well as social and occupational impairment. For each item the participant can respond with a rating of 0-8 (with 0 indicating no symptom severity and frequency and 8 indicating extreme symptom severity and frequency). The range of total scores on a CAPS is from 0-136, with a greater score indicating greater PTSD symptom severity. The total score is computed by summing the aforementioned 17 items. Additionally, the CAPS assesses for a positive PTSD diagnosis by assessing for the three DSM-IV criteria of B, C, and D. In order to meet a positive screen for each criteria, a person must screen positive for symptoms by reporting a score of 3 or more on the specific symptom criterion.
Measured: Baseline and 1 month posttreatment
Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
The CAPS is administered to assess the frequency and intensity of PTSD symptoms at baseline, and then again 3 months posttreatment. The CAPS is a 25 item semi-structured interview that assesses the 17 DSM-IV PTSD criteria as well as social and occupational impairment. For each item the participant can respond with a rating of 0-8 (with 0 indicating no symptom severity and frequency and 8 indicating extreme symptom severity and frequency). The range of total scores on a CAPS is from 0-136, with a greater score indicating greater PTSD symptom severity. The total score is computed by summing the aforementioned 17 items. Additionally, the CAPS assesses for a positive PTSD diagnosis by assessing for the three DSM-IV criteria of B, C, and D. In order to meet a positive screen for each criteria, a person must screen positive for symptoms by reporting a score of 3 or more on the specific symptom criterion.
Measured: change in CAPS score from baseline to 3 months posttreatment
Secondary outcomes (4)
PTSD Checklist (PCL)
Self-report instrument which assesses the intensity of Posttraumatic Stress Disorder symptoms. The PCL measures the 17 DSM-IV PTSD criteria in 17 items. For each item the participant can respond with a rating of 1-5 (with 1 indicating not at all bothered 5 indicating extremely bothered by the symptom) The range of total scores on the PCL is from 17-85, with a greater score indicating greater PTSD symptom severity. The total score is computed by summing the aforementioned 17 items.
Measured: change in PCL score from baseline to 1 month posttreatment
PTSD Checklist (PCL)
Self-report instrument which assesses the intensity of Posttraumatic Stress Disorder symptoms. The PCL measures the 17 DSM-IV PTSD criteria in 17 items. For each item the participant can respond with a rating of 1-5 (with 1 indicating not at all bothered 5 indicating extremely bothered by the symptom) The range of total scores on the PCL is from 17-85, with a greater score indicating greater PTSD symptom severity. The total score is computed by summing the aforementioned 17 items.
Measured: change in PCL score from baseline to 3 months posttreatment
Quick Inventory of Depressive Symptomatology (QIDS)
The QIDS is a 16-item self-report measure that assesses how much a participant endorses each of the DSM-IV-TR symptoms of depression, with each item scored from 0 (no endorsement of symptom) to 3 (endorsement of severe symptomatology). Scores on the QIDS range from 0-27, with higher scores indicating higher depressive symptom severity.
Measured: change in QIDS score from baseline to 1 month posttreatment
Quick Inventory of Depressive Symptomatology (QIDS)
The QIDS is a 16-item self-report measure that assesses how much a participant endorses each of the DSM-IV-TR symptoms of depression, with each item scored from 0 (no endorsement of symptom) to 3 (endorsement of severe symptomatology). Scores on the QIDS range from 0-27, with higher scores indicating higher depressive symptom severity.
Measured: change in QIDS score from baseline to 3 months posttreatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2011 (estimated)
- Study startAug 2008
- Primary completionJul 2010
- Study completionJul 2010
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- North Texas Veterans Healthcare System
- Responsible party
- Principal investigator, Alina Suris, University of Texas Southwestern Medical Center
- Investigators
- Alina M Suris, Ph.D., Principal investigator, UT Southwestern Medical Center; VA North Texas Healthcare SystemCarol North, M.D., Study chair, UT Southwestern Medical Center; VA North Texas Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01449955
- Sponsor's protocol ID
- 08-049
- Status last verified
- Jun 2018
- First submitted
- 16 Sep 2011
- Last updated
- 18 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Blundell J, Kouser M, Powell CM. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem. 2008 Jul;90(1):28-35. doi: 10.1016/j.nlm.2007.12.004. Epub 2008 Mar 7.
PubMed 18316213Suris A, Smith J, Powell C, North CS. Interfering with the reconsolidation of traumatic memory: sirolimus as a novel agent for treating veterans with posttraumatic stress disorder. Ann Clin Psychiatry. 2013 Feb;25(1):33-40.
PubMed 23376868
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- mTOR Kinase as a Therapeutic Target in Reconsolidation of Posttraumatic Stress Disorder-related Traumatic Memory
- ClinicalTrials.gov ID
- NCT01449955
- Acronym / sponsor ID
- 08-049
- Conditions
- Posttraumatic Stress Disorder
- Keywords
- PTSD
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- North Texas Veterans Healthcare System
- Study start
- Aug 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 10 Oct 2011 (estimated)
- Results
- Posted 30 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the proposed study is to determine if pairing reactivation of a traumatic memory with a single administration of Rapamycin (e.g., Sirolimus) in men with combat-related Posttraumatic Stress Disorder leads to a reduction of the emotional strength of that particular traumatic memory.
The following hypotheses will be tested:
- Traumatic memory reactivation paired with a single dose of Rapamycin will decrease objective measures of stress and self-report of stress during replay of the traumatic memory, relative to, subjects receiving placebo.
- Pairing administration of Rapamycin with traumatic memory reactivation will decrease symptoms of Posttraumatic Stress Disorder one month and three months later, relative to patients receiving placebo.
Detailed description
Post-traumatic stress disorder (PTSD) is characterized by intrusive memories in the form of unwanted images, nightmares, and flashbacks as the result of being exposed to a traumatic event . Current research efforts have begun to explore the underlying neurochemical changes associated with PTSD. Recently, these efforts have focused on the prevention of PTSD in persons exposed to trauma. For example, preliminary evidence suggests that interference with consolidation of trauma-related memories using the beta-antagonist, propranolol, may prevent PTSD in humans with recent traumas. However, given that as much as 90% of the US population is exposed to at least one traumatic event during their lifetimes, the utility of this treatment is limited by the logistical problems of treating everyone at risk. To date, there have been very few systematic studies on humans that focus on changing the underlying traumatic memory once PTSD has been established.
The trauma experience is initially stored in short-term memory, then consolidated into long-term memory. However, the long-term stability conferred by the consolidation process undergoes a period of labiality as follows. Each time a consolidated memory is activated, the memory trace becomes newly labile and must be consolidated again to remain in long-term memory5. This process is called reconsolidation. Reconsolidation therefore offers a biologic window during which long-term memories can be disrupted. Preclinical studies have begun to unravel the biological changes that underlie these processes. Both pharmacological agents, including glucocorticoids, and protein synthesis inhibitors can interfere with memory consolidation and reconsolidation. In preclinical studies, the global protein synthesis inhibitor anisomycin can block reconsolidation, leading to a reduction in strength of traumatic memories. Unfortunately, the toxicity of anisomycin is prohibitive for therapeutic use. Thus, rather than using a global protein synthesis inhibitor, a more effective and selective means of reducing consolidation of an established traumatic memory is to target only a subset of protein translation important for synaptic plasticity. The protein kinase mTOR (mammalian target of rapamycin) is just such a regulator of a subset of protein synthesis critical for synaptic plasticity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (e.g., sugar pill) | Placebo comparator | Drug: Placebo15 mg Placebo will be administered once, in pill form. |
| Rapamycin | Active comparator | Drug: Rapamycin15 mg of Rapamycin will be administered once, in pill form. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male Veterans
- Diagnosis of Posttraumatic Stress Disorder related to combat
Key exclusion criteria (6 listed)
- Hypersensitivity to Rapamycin
- Organic brain damage (including unresolved Traumatic Brain Injury sequela)
- Substance dependence in the last three months
- On any immunosuppressant therapy
- Prominent suicidal or homicidal features
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 |
|---|---|---|
| RapamycinAlso: Sirolimus, X-RapamuneSirolimus is an FDA approved immunosuppressant drug used to prevent rejection in organ transplantation, and is especially useful in kidney transplants. It is non-toxic to kidneys, unlike other immunosuppressants. In this study, the medication will be administered once to see if it interferes with emotional memory reconsolidation. This is based on the fact that it inhibits the mammalian target of Rapamycin (mTOR) through directly binding the mTOR Complex1 (mTORC1). mTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis and transcription. a single dosage of 15mg will be administered during this study. | Drug | Rapamycin |
| PlaceboAlso: sugar pillInactive | Drug | Placebo (e.g., sugar pill) |
Primary outcome
Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
Time frame: Baseline and 1 month posttreatment
Clinician administered interview which assesses the symptoms of Posttraumatic Stress disorder at baseline, and then again 1 month posttreatment. The CAPS is a 25 item semi-structured interview that assesses the 17 DSM-IV PTSD criteria as well as social and occupational impairment. For each item the participant can respond with a rating of 0-8 (with 0 indicating no symptom severity and frequency and 8 indicating extreme symptom severity and frequency). The range of total scores on a CAPS is from 0-136, with a greater score indicating greater PTSD symptom severity. The total score is computed by summing the aforementioned 17 items. Additionally, the CAPS assesses for a positive PTSD diagnosis by assessing for the three DSM-IV criteria of B, C, and D. In order to meet a positive screen for each criteria, a person must screen positive for symptoms by reporting a score of 3 or more on the specific symptom criterion.
Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
Time frame: change in CAPS score from baseline to 3 months posttreatment
The CAPS is administered to assess the frequency and intensity of PTSD symptoms at baseline, and then again 3 months posttreatment. The CAPS is a 25 item semi-structured interview that assesses the 17 DSM-IV PTSD criteria as well as social and occupational impairment. For each item the participant can respond with a rating of 0-8 (with 0 indicating no symptom severity and frequency and 8 indicating extreme symptom severity and frequency). The range of total scores on a CAPS is from 0-136, with a greater score indicating greater PTSD symptom severity. The total score is computed by summing the aforementioned 17 items. Additionally, the CAPS assesses for a positive PTSD diagnosis by assessing for the three DSM-IV criteria of B, C, and D. In order to meet a positive screen for each criteria, a person must screen positive for symptoms by reporting a score of 3 or more on the specific symptom criterion.
4 secondary outcomes
PTSD Checklist (PCL)
Time frame: change in PCL score from baseline to 1 month posttreatment
PTSD Checklist (PCL)
Time frame: change in PCL score from baseline to 3 months posttreatment
Quick Inventory of Depressive Symptomatology (QIDS)
Time frame: change in QIDS score from baseline to 1 month posttreatment
Quick Inventory of Depressive Symptomatology (QIDS)
Time frame: change in QIDS score from baseline to 3 months posttreatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18316213Blundell J, Kouser M, Powell CM. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol Learn Mem. 2008 Jul;90(1):28-35. doi: 10.1016/j.nlm.2007.12.004. Epub 2008 Mar 7.
- Results publication: PubMed 23376868Suris A, Smith J, Powell C, North CS. Interfering with the reconsolidation of traumatic memory: sirolimus as a novel agent for treating veterans with posttraumatic stress disorder. Ann Clin Psychiatry. 2013 Feb;25(1):33-40.
Related trials for Posttraumatic Stress Disorder
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Not yet recruiting
A Transdiagnostic Sleep Health Intervention for Veterans With PTSD
Stress Disorders, Post-Traumatic, Sleep Initiation and Maintenance Disorders
Not yet recruitingPhase 3
Women Who Are Victims of Violence: Treatment of PTSD Through Reactivation of Traumatic Memories Using Propranolol
Post-Traumatic Stress Disorder, PTSD
Recruiting
Advancing Skills Through Consultation, Education, and Novel Technologies
PTSD - Post Traumatic Stress Disorder
RecruitingPhase 2/3
Redefine Study: A Study Evaluating the Efficacy, Safety, and Tolerability of COMP360 in Participants With Post-traumatic Stress Disorder
PTSD - Post Traumatic Stress Disorder, PTSD
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.
Alina M Suris, Ph.D. principal investigator
UT Southwestern Medical Center; VA North Texas Healthcare System
Carol North, M.D. study chair
UT Southwestern Medical Center; VA North Texas Healthcare System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rapamycin in people with Posttraumatic Stress Disorder, run by University of Texas Southwestern Medical Center 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 2 inclusion and 6 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: finished, as of the sponsor's last update on 18 Jul 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2014). 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?
Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) (time frame: Baseline and 1 month posttreatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01449955, which also lists 2 linked publications.
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 18 Jul 2018.