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Posttraumatic Stress DisorderLOSe-PTSDNCT02709018

A Controlled Trial of Losartan in Posttraumatic Stress Disorder

A study testing losartan in people with Posttraumatic Stress Disorder, run by University of California, San Diego at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Posttraumatic Stress Disorder
What is being tested?
losartan
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
149 participants
Where
6 sitesUnited States
Study dates
16 Jul 2016to 29 Sep 2020
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must be a man or woman between 18 and 70 years of age, inclusive.
  • Subjects must have a primary DSM-5 diagnosis of Posttraumatic Stress Disorder.
  • Subjects must have a Clinical Administered PTSD Scale for PTSD (CAPS-5) ≥ 25 persistent at Screening for at least 3 months duration.
  • Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
  • Subject must be willing and able to fill out self-administered questionnaires.
  • Subject must be able to be compliant with self-administration of medication.
  • Subject must be able to swallow the study medication whole with aid of water.
  • 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.

Who cannot join

  • Subjects who have current or imminent risk of suicide as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) at each study visit.
  • Subject with active psychosis.
  • Subject has a history of moderate or severe drug or alcohol use disorder according to DSM-5 criteria within 3 months before screening.
  • Subject has a history of allergy to losartan or other angiotensin receptor blockers (ARBs).
  • 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.
  • 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.
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  • 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.
  • 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.
  • Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant.
  • Subject is unable to comply with the study-specific requirements
  • Subjects with abnormal liver, renal or EKG findings as determined by physician.
  • Subject exhibits clinically-significant hypertension as determined by medical evaluation and/or BP > 190/100.
  • Systolic Blood Pressure (SBP) < 90mmHg.
  • Liver function Tests (LFT's) > 2 times the upper limit of normal.
  • Patients with Chronic Kidney Disease 4, as determined by history, baseline labs (including eGFR < 45ml/minute) and evaluation by a physician will be excluded

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • McLean Hospital

    Belmont, Massachusetts, 02478

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of California, San Diego

    La Jolla, California, 92037

  • New York University Langone Health

    New York, New York, 10016

  • George Washington University

    Washington D.C., District of Columbia, 20037

Other trials in United States

About this study

Official title: Enhancing Fear Extinction Via Angiotensin Type 1 Receptor Inhibition: A Randomized Controlled Trial in Posttraumatic Stress Disorder

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.

Read the 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.

Being tested
losartan, Placebo
Keywords
posttraumatic stress disorder, losartan, angiotensin receptor blocker
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.

  • losartanDrug

    Also called Cozaar

    Angiotensin receptor blocker (ARB)

  • PlaceboDrug

    Placebo

Study groups in NCT02709018
Study groupRoleWhat they receive
LosartanExperimentalLosartan flexibly dosed from 25-100 mg per day over 10 weeks
Receives: Drug: losartan
PlaceboPlacebo comparatorPlacebo flexibly dosed from 25-100 mg per day over 10 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    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.

    The CAPS-5 as used here has 20 items, each scored 0-4, to yield a score with a possible range of 0-80. Higher scores mean worse outcome.

    Measured: 10 weeks

Secondary outcomes (1)
  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.

    The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) as used here has 20 items, each scored 0-4, to yield a score with a possible range of 0-80. Higher scores mean worse outcome.

    Measured: 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2016 (estimated)
  2. Study start16 Jul 2016
  3. Primary completion29 Feb 2020
  4. Study completion29 Sep 2020

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
149 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02709018
Sponsor's protocol ID
W81XWH-15-2-0090
Acronym
LOSe-PTSD
Status last verified
Feb 2021
First submitted
7 Mar 2016
Last updated
12 Mar 2021
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Khoury NM, Marvar PJ, Gillespie CF, Wingo A, Schwartz A, Bradley B, Kramer M, Ressler KJ. The renin-angiotensin pathway in posttraumatic stress disorder: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms. J Clin Psychiatry. 2012 Jun;73(6):849-55. doi: 10.4088/JCP.11m07316. Epub 2012 May 1.

    PubMed 22687631
  • Krause EG, de Kloet AD, Scott KA, Flak JN, Jones K, Smeltzer MD, Ulrich-Lai YM, Woods SC, Wilson SP, Reagan LP, Herman JP, Sakai RR. Blood-borne angiotensin II acts in the brain to influence behavioral and endocrine responses to psychogenic stress. J Neurosci. 2011 Oct 19;31(42):15009-15. doi: 10.1523/JNEUROSCI.0892-11.2011.

    PubMed 22016534
  • Llano Lopez LH, Caif F, Garcia S, Fraile M, Landa AI, Baiardi G, Lafuente JV, Braszko JJ, Bregonzio C, Gargiulo PA. Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats. Pharmacol Rep. 2012;64(1):54-63. doi: 10.1016/s1734-1140(12)70730-2.

    PubMed 22580520
  • Saavedra JM, Sanchez-Lemus E, Benicky J. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications. Psychoneuroendocrinology. 2011 Jan;36(1):1-18. doi: 10.1016/j.psyneuen.2010.10.001. Epub 2010 Oct 29.

    PubMed 21035950
  • Nylocks KM, Michopoulos V, Rothbaum AO, Almli L, Gillespie CF, Wingo A, Schwartz AC, Habib L, Gamwell KL, Marvar PJ, Bradley B, Ressler KJ. An angiotensin-converting enzyme (ACE) polymorphism may mitigate the effects of angiotensin-pathway medications on posttraumatic stress symptoms. Am J Med Genet B Neuropsychiatr Genet. 2015 Jun;168B(4):307-15. doi: 10.1002/ajmg.b.32313. Epub 2015 Apr 29.

    PubMed 25921615
  • Hurt RC, Garrett JC, Keifer OP Jr, Linares A, Couling L, Speth RC, Ressler KJ, Marvar PJ. Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear. Genes Brain Behav. 2015 Sep;14(7):526-33. doi: 10.1111/gbb.12235. Epub 2015 Aug 25.

    PubMed 26257395
  • Marvar PJ, Goodman J, Fuchs S, Choi DC, Banerjee S, Ressler KJ. Angiotensin type 1 receptor inhibition enhances the extinction of fear memory. Biol Psychiatry. 2014 Jun 1;75(11):864-72. doi: 10.1016/j.biopsych.2013.08.024. Epub 2013 Oct 4.

    PubMed 24094510
  • Stein MB, Jain S, Simon NM, West JC, Marvar PJ, Bui E, He F, Benedek DM, Cassano P, Griffith JL, Howlett J, Malgaroli M, Melaragno A, Seligowski AV, Shu IW, Song S, Szuhany K, Taylor CT, Ressler KJ; LOSe-PTSD Investigators. Randomized, Placebo-Controlled Trial of the Angiotensin Receptor Antagonist Losartan for Posttraumatic Stress Disorder. Biol Psychiatry. 2021 Oct 1;90(7):473-481. doi: 10.1016/j.biopsych.2021.05.012. Epub 2021 May 21.

    PubMed 34275593

Questions about this trial

What is this clinical trial studying?

A study testing losartan in people with Posttraumatic Stress Disorder, run by University of California, San Diego at 6 sites 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 8 inclusion and 15 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 12 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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 12 Mar 2021). 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?

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). 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 NCT02709018, which also lists 8 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 12 Mar 2021.

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