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A Controlled Trial of Losartan in Posttraumatic Stress Disorder (LOSe-PTSD)

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ClinicalTrials.gov Identifier: NCT02709018
Recruitment Status : Recruiting
First Posted : March 15, 2016
Last Update Posted : February 12, 2019
Sponsor:
Collaborators:
Mclean Hospital
Massachusetts General Hospital
Henry M. Jackson Foundation, Walter Reed National Military Medical Center
Atlanta Research and Education Foundation
NYU Langone Health
George Washington University
Information provided by (Responsible Party):
Murray B. Stein, University of California, San Diego

Brief Summary:
This study is being conducted to determine if losartan, an angiotensin receptor blocker (ARB), is safe and effective in the treatment of posttraumatic stress disorder (PTSD) symptoms. The study is also intended to determine if certain genetic markers are useful in predicting PTSD symptom reduction with losartan. Approximately 160 subjects with chronic PTSD ages 18-65 will participate in this study across five sites. Subjects will be assigned by chance to take either flexibly dosed losartan (up to a maximum dosage of 100 mg) or placebo (which resembles the study drug but has no active ingredients), once a day for 10 weeks. Furthermore, it is hypothesized that CC homozygotes for rs4311 SNP in the ACE gene will have a superior response to losartan on PTSD symptoms compared to T carriers.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Drug: losartan Drug: Placebo Not Applicable

Detailed Description:
There are limited current treatments available for PTSD, and the only FDA-approved medications are SSRIs, which were empirically found to be somewhat helpful. Losartan provides a potentially important and exciting development in that it is readily available, safe, inexpensive (available as a generic drug), and has a neurobiological mechanism based on recent exciting discoveries, as outlined below. This proposal is designed to test, in a multisite RCT, this novel, mechanistically-determined, safe and well-tolerated, potentially powerful treatment for PTSD symptoms.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Enhancing Fear Extinction Via Angiotensin Type 1 Receptor Inhibition: A Randomized Controlled Trial in Posttraumatic Stress Disorder
Study Start Date : July 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Losartan
Losartan flexibly dosed from 25-100 mg per day over 10 weeks
Drug: losartan
Angiotensin receptor blocker (ARB)
Other Name: Cozaar

Placebo Comparator: Placebo
Placebo flexibly dosed from 25-100 mg per day over 10 weeks
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. The primary outcome for this study is mean change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) over the treatment period of 10 weeks between the losartan arm and the placebo arm. [ Time Frame: 10 weeks ]
    Clinician-Administered PTSD Scale for DSM-5 also known as CAPS 5 is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to, make current (past month) diagnosis of PTSD, make a lifetime diagnosis of PTSD and assess PTSD symptoms over the past week


Secondary Outcome Measures :
  1. Change in CAPS-5 associated with CC homozygosity for rs4311 SNP in the angiotensin converting enzyme gene (ACE) compared to T carriers, among subjects randomized to losartan. [ Time Frame: 10 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

[Below is a synopsis of relevant eligibility criteria. For details please refer to the protocol by contacting the Principal Investigator]

Inclusion Criteria

  1. Subject must be a man or woman between 18 and 70 years of age, inclusive.
  2. Subjects must have a primary DSM-5 diagnosis of Posttraumatic Stress Disorder.
  3. Subjects must have a Clinical Administered PTSD Scale for PTSD (CAPS-5) ≥ 25 persistent at Screening for at least 3 months duration.
  4. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
  5. Subject must be willing and able to fill out self-administered questionnaires.
  6. Subject must be able to be compliant with self-administration of medication.
  7. Subject must be able to swallow the study medication whole with aid of water.
  8. Subject must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria

  1. Subjects who have current or imminent risk of suicide as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) at each study visit.
  2. Subject with active psychosis.
  3. Subject has a history of moderate or severe drug or alcohol use disorder according to DSM-5 criteria within 3 months before screening.
  4. Subject has a history of allergy to losartan or other angiotensin receptor blockers (ARBs).
  5. Subject has a medical illness likely to result in imminent hospitalization or for which treatments are contraindicated based on lab results, medical history and physical exam.
  6. Subject has serious cognitive impairment felt likely to interfere with the ability to participate meaningfully in the study. Participants with mild to moderate traumatic brain injury (TBI) will not be excluded from the study. Only those who evidence significant cognitive impairment at Screening (as evidenced by confusion, inability to track discussion or answer questions, or other clear and significant indicators of cognitive impairment) will be excluded.
  7. Concurrent ACE Inhibitors or Angiotensin Receptor Blockers or Prazosin; patients on other antihypertensives may be enrolled if, after consultation with their prescribing physician, it is determined that the addition of losartan would not be contraindicated.
  8. Concurrent antidepressants or antipsychotics. Subjects, who have elected, in consultation with their health care provider, to discontinue any antidepressants or antipsychotics, must be off the medications for a minimum of 2 weeks prior to study randomization. Stable bedtime doses of sleep agents (e.g., trazodone ≤ 200mg; eszopiclone; zolpidem; lorazepam) will be allowed as long as the dose has been stable for at least 2 weeks prior to study randomization. Benzodiazepines taken for other than sleep are not permitted.
  9. Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant.
  10. Subject is unable to comply with the study-specific requirements
  11. Subjects with abnormal liver, renal or EKG findings as determined by physician.
  12. Subject exhibits clinically-significant hypertension as determined by medical evaluation and/or BP > 190/100.
  13. Systolic Blood Pressure (SBP) < 90mmHg.
  14. Liver function Tests (LFT's) > 2 times the upper limit of normal.
  15. Patients with Chronic Kidney Disease 4, as determined by history, baseline labs (including eGFR < 45ml/minute) and evaluation by a physician will be excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02709018


Contacts
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Contact: Murray B Stein, MD, MPH 858-534-6451 mstein@ucsd.edu
Contact: Farah D Shaikh, MD, DrPH 858-246-0623 fshaikh@ucsd.edu

Locations
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United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92037
Contact: Farah D Shaikh, MD, Dr.PH    858-246-0623    fshaikh@ucsd.edu   
Contact: Nuzhat A Beg, MD    858-534-7068    nbeg@ucsd.edu   
Principal Investigator: Murray B Stein, MD, MPH         
United States, District of Columbia
George Washington University Recruiting
Washington, District of Columbia, United States, 20037
Contact: Nicole Swanson    202-741-2437    loseptsd@gwu.edu   
Principal Investigator: Suzan Song, MD, MPH, PhD         
United States, Georgia
Atlanta Veterans Affairs Medical Center Withdrawn
Atlanta, Georgia, United States, 30033
United States, Maryland
Walter Reed National Military Medical Center Recruiting
Bethesda, Maryland, United States, 20889
Contact: Eva Asabre, MPH    301-295-2381    eva.asabre.ctr@usuhs.edu   
Contact: Ashley Phares, BA    (301) 295-2381    ashley.phares.ctr@usuhs.edu   
Principal Investigator: James West, MD         
United States, Massachusetts
McLean Hospital Recruiting
Belmont, Massachusetts, United States, 02478
Contact: Emily Melen, BA    617-855-2511    EMELLEN@MCLEAN.HARVARD.EDU   
Principal Investigator: Kerry Ressler, MD, PhD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Emma R Toner, BA    617-726-1570    ertoner@mgh.harvard.edu   
Principal Investigator: Eric Bui, MD, PhD         
United States, New York
New York University Langone Health Recruiting
New York, New York, United States, 10016
Contact: Julia Spandorfer, BA    646-754-4895    Julia.Spandorfer@nyumc.org   
Contact: Rebecca Lubin, AB    646-754-7035    Rebecca.Lubin@nyumc.org   
Principal Investigator: Naomi Simon, MD, MSc         
Sponsors and Collaborators
University of California, San Diego
Mclean Hospital
Massachusetts General Hospital
Henry M. Jackson Foundation, Walter Reed National Military Medical Center
Atlanta Research and Education Foundation
NYU Langone Health
George Washington University
Investigators
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Principal Investigator: Murray B Stein, MD, MPH University of California, San Diego
Study Chair: Kerry J Ressler, MD, PhD McLean Hospital and Harvard Medical School

Publications:

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Responsible Party: Murray B. Stein, Professor of Psychiatry, Family Medicine and Public Health, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02709018     History of Changes
Other Study ID Numbers: W81XWH-15-2-0090
First Posted: March 15, 2016    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Murray B. Stein, University of California, San Diego:
posttraumatic stress disorder
losartan
angiotensin receptor blocker

Additional relevant MeSH terms:
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Disease
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Pathologic Processes
Trauma and Stressor Related Disorders
Mental Disorders
Losartan
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action