Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD)

• Status: Not yet recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

There is large body of evidence demonstrating that Posttraumatic Stress Disorder (PTSD) is associated with alterations in the stress hormone cortisol. There is also evidence that medications that block cortisol may be beneficial for treating PTSD and depression. The VA recently completed a study of a mifepristone, a medication that blocks cortisol and progesterone hormones, and found some benefit for Veterans who did not have a history of traumatic brain injury. The proposal will test a medication from a new class of cortisol blockers which have no effect on progesterone. The proposed study will test the drug CORT108297 for treatment of PTSD and will establish a safety profile that will inform the design of future studies.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Office of Research and Development
• Collaborator: James J. Peters Veterans Affairs Medical Center

Criteria

Inclusion Criteria:

• History of US military service

• Capable of reading and understanding English

• Able to provide written informed consent

• Criterion A event meets DSM-5 criteria and occurred during military service, including combat and military sexual trauma

• Chronic full syndromal PTSD diagnosis >3 months duration as indexed by CAPS-5 at screening, and CAPS-5 score > 26 CAPS-5 total score for the past week at baseline

• Participants (male or pre-menopausal females) agree to use two forms of reliable contraception, one of which is a barrier method

• Participants may be on a stable dose (8 weeks at minimum) of an SSRI or SNRI for treatment of their PTSD

• Participants may be on a stable dose of trazodone for sleep maintenance.

• If pain medications are required (opiates), the dose must be stable for 4 weeks at minimum

• For participants who are in psychotherapy, treatment must be stable for 6 weeks

Exclusion Criteria:

• DSM-5 alcohol, marijuana, and/or other drug use disorder in the last 3 months

• Mild alcohol and marijuana use not meeting criteria for use disorder will be allowed

• Lifetime bipolar disorder I or II, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features

• Exposure to trauma in the last 3 months

• Use of exclusionary antidepressant (mirtazapine, doxepin, tricyclics), mood stabilizers (e.g., lithium), antipsychotic medication, benzodiazepines

• Prominent suicidal or homicidal ideation or any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS) or increased risk of suicide that necessitates additional therapy or inpatient treatment

• Pre-existing sleep apnea in the absence of adherence to effective treatment (such as CPAP or oral device) or positive screen for sleep apnea by type III device

• Veteran has a medical condition that requires the use of corticosteroids (oral or inhaled)

• Neurologic disorder or systemic illness affecting CNS function

• Chronic or unstable medical illness including unstable angina, myocardial infarction within the past 6 months, congestive heart failure, preexisting hypotension or orthostatic hypotension

• heart block or arrhythmia

• chronic renal or hepatic failure, and pancreatitis

• severe chronic obstructive pulmonary disease

• History of hepatobiliary disease or an AST or ALT greater than 2x the upper limit of normal, History of renal disease or an eGFR of less than 60 ml/min

• A prolonged QTc >450 msec on ECG at screening

• History of additional risk factors for Torsades de pointes

• e.g., heart failure, hypokalemia, family history of long QT syndrome

• Participants who may require the use of concomitant medications that prolong the QT/QTc interval

• Use of concomitant medications that might increase the plasma concentration of CORT108297

• e.g., use of strong inhibitors of CYP3A such as Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir

• Poorly controlled hypertension

• Poorly controlled diabetes mellitus

• History of moderate or severe traumatic brain injury

• Mild cognitive impairment assessed by the Montreal Cognitive Assessment