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| Name | Class |
|---|---|
| North Texas Veterans Healthcare System | FED |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo (e.g., sugar pill) | Placebo Comparator | 15 mg Placebo will be administered once, in pill form. |
|
| Rapamycin | Active Comparator | 15 mg of Rapamycin will be administered once, in pill form. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rapamycin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | change in CAPS score from baseline to 3 months posttreatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alina M Suris, Ph.D. | UT Southwestern Medical Center; VA North Texas Healthcare System | Principal Investigator |
| Carol North, M.D. | UT Southwestern Medical Center; VA North Texas Healthcare System | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA North Texas Healthcare System | Dallas | Texas | 75216 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18316213 | Background | 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. | |
| 23376868 | Result | Suris 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. |
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excluded if did not meet PTSD criteria according to the CAPS
Recruited by flyers, clinician referral and letters mailed to male VA North Texas patients with PTSD.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rapamycin (e.g., Sirolimus) | 15mg Rapamycin administered once in pill form |
| FG001 | Placebo | 15mg Placebo administered once in pill form |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Male Veterans with PTSD
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| ID | Title | Description |
|---|---|---|
| BG000 | Rapamycin | 15mg Rapamycin administered once in pill form |
| BG001 | Placebo | 15mg Placebo administered once in pill form |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | scores on a scale | Baseline and 1 month posttreatment |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rapamycin | 15mg Rapamycin |
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Timing of medication administration may not have been optimal and relatively small sample size
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Alina Suris | UT Southwestern/VA North Texas | 214-857-0334 | alina.suris@va.gov |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D020123 | Sirolimus |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D002241 | Carbohydrates |
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|
|
| Placebo | Drug | Inactive |
|
|
| 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. | 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. | 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. | change in QIDS score from baseline to 3 months posttreatment |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Rapamycin (e.g., Sirolimus) |
15mg Rapamycin administered once in pill form |
| OG001 | Placebo | 15 mg Placebo administered once in pill form |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | units on a scale | change in CAPS score from baseline to 3 months posttreatment |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | change in PCL score from baseline to 1 month posttreatment |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | change in PCL score from baseline to 3 months posttreatment |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | change in QIDS score from baseline to 1 month posttreatment |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | change in QIDS score from baseline to 3 months posttreatment |
|
|
|
|
| 0 |
| 28 |
| 0 |
| 28 |
| EG001 | Placebo | Placebo arm | 0 | 26 | 0 | 26 |
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