Rapamycin as a Means of Interference With Reconsolidation of Posttraumatic Stress Disorder-related Traumatic Memory

NCT01449955 | Completed Results DMC

• 1 other identifier: 08-049
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief 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. The following hypotheses will be tested:

1. 1.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.
2. 2.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.

Conditions

Posttraumatic Stress Disorder

Keywords

PTSD

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (4)

• PTSD Checklist (PCL)

  change in PCL score from baseline to 1 month posttreatment

• PTSD Checklist (PCL)

  change in PCL score from baseline to 3 months posttreatment

• Quick Inventory of Depressive Symptomatology (QIDS)

  change in QIDS score from baseline to 1 month posttreatment

• Quick Inventory of Depressive Symptomatology (QIDS)

  change in QIDS score from baseline to 3 months posttreatment

Study Arms (2)

Placebo (e.g., sugar pill)

PLACEBO COMPARATOR

15 mg Placebo will be administered once, in pill form.

Drug: Placebo

Rapamycin

ACTIVE COMPARATOR

15 mg of Rapamycin will be administered once, in pill form.

Drug: Rapamycin

Interventions

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.

Also known as: Sirolimus, X-Rapamune

Rapamycin

Placebo DRUG

Inactive

Also known as: sugar pill

Placebo (e.g., sugar pill)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male Veterans
• Diagnosis of Posttraumatic Stress Disorder related to combat

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• North Texas Veterans Healthcare System: collaborator

Study Sites (1)

VA North Texas Healthcare System

Dallas, Texas, 75216, United States

Location

Related Publications (2)

• 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.

  PMID: 18316213 BACKGROUND

• 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.

  PMID: 23376868 RESULT

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Sirolimus; Sugars

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Carbohydrates

Limitations and Caveats

Timing of medication administration may not have been optimal and relatively small sample size

Results Point of Contact

• Title: Dr. Alina Suris
• Organization: UT Southwestern/VA North Texas

alina.suris@va.gov

214-857-0334

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: October 10, 2011
• Study Start: August 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: July 18, 2018
• Results First Posted: January 30, 2014

Record last verified: 2018-06

Locations

US (1)