NCT02709018.

Methods	A controlled trial of Losartan in posttraumatic stress disorder (LOSe‐PTSD) Study type: Interventional Study phase: Not applicable Allocation: Randomised Intervention model: Parallel assignment Masking: quadruple (participant, care provider, investigator, outcomes assessor) Primary purpose: Treatment
Participants	Inclusion criteria; Person must be a man or woman between 18 and 70 years of age, inclusive; must have a primary DSM‐5 diagnosis of Posttraumatic Stress Disorder; must have a Clinical Administered PTSD Scale for PTSD (CAPS‐5) ≥ 25 persistent at screening for at least 3 months duration; person must be willing and able to adhere to the prohibitions and restrictions specified in this protocol; 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; 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: Persons who have current or imminent risk of suicide as assessed by the Columbia‐Suicide Severity Rating Scale (C‐SSRS) at each study visit; person with active psychosis; has a history of moderate or severe drug or alcohol use disorder according to DSM‐5 criteria within 3 months before screening; has a history of allergy to losartan or other angiotensin receptor blockers (ARBs); has a medical illness likely to result in imminent hospitalisation or for which treatments are contraindicated based on lab results, medical history and physical exam; 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 with evidence of 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; 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. People who have elected, in consultation with their healthcare provider, to discontinue any antidepressants or antipsychotics, must be off the medications for a minimum of 2 weeks prior to study randomisation. Stable bedtime doses of sleep agents (e.g., trazodone ≤ 200 mg; eszopiclone; zolpidem; lorazepam) will be allowed as long as the dose has been stable for at least 2 weeks prior to study randomisation. Benzodiazepines taken for other than sleep are not permitted; Person is a woman who is pregnant, or breast‐feeding, or planning to become pregnant; is unable to comply with the study‐specific requirements; people with abnormal liver, renal or EKG findings as determined by physician; person exhibits clinically‐significant hypertension as determined by medical evaluation and/or BP > 190/100; systolic blood pressure (SBP) < 90 mmHg; liver function tests (LFT's) > 2 times the upper limit of normal; People with chronic kidney disease 4, as determined by history, baseline labs (including eGFR < 45 ml/minute) and evaluation by a physician will be excluded
Interventions	Experimental: losartan Losartan flexibly‐dosed from 25 ‐ 100 mg per day over 10 weeks Intervention: Drug: losartan Placebo comparator: placebo Placebo flexibly dosed from 25 ‐ 100 mg per day over 10 weeks Intervention: drug: Placebo
Outcomes	Primary outcome measures: 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: Change in CAPS‐5 associated with CC homozygosity for rs4311 SNP in the angiotensin converting enzyme gene (ACE) compared to T carriers, among participants randomised to losartan. (Time frame: 10 weeks)
Notes	Starting date: July 2016 Contact information: Investigators: Murray B Stein, MD, MPH., University of California, San Diego; Kerry J Ressler, MD., McLean Hospital and Harvard Medical School Responsible parties: 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 New York University School of Medicine, George Washington University Estimated primary completion date: September 2019 Estimated study completion date: September 2019