Clinical trial NCT04452500: Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD) (Seven Study)
Official title: Phase IIa Trial of a Selective Glucocorticoid Receptor Antagonist in the Treatment of Veterans With Posttraumatic Stress Disorder (PTSD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: PTSD
Keywords: Glucocorticoids
Posttraumatic Stress Disorder
Quality of Life
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2020-06-30
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators propose a two-site parallel group, randomized, double-blind, placebo-controlled Phase IIa clinical trial to test the efficacy and safety of CORT108297- 180mg daily for 7 days for PTSD symptoms in Veterans.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test the drug CORT108297, which blocks the hormone cortisol, for treatment of PTSD in Veterans, and establish a safety profile that will inform the design of future studies.

Detailed description: This is a randomized, double-blind, placebo-controlled Phase IIa clinical trial to test the efficacy and safety of CORT108297- 180mg daily for 7 days for PTSD symptoms in Veterans. Each of the two sites will enroll 44 Veterans with chronic PTSD. Participants first will undergo screening procedures, including a clinical psychological interview, self-report questionnaires, blood draw, and medical evaluations. If eligible, they will be randomized to either CORT108297 or placebo. The same procedures will be repeated at several in-person and virtual visits before, during and after taking the study drug or placebo for seven days. The key outcome measures will be obtained at baseline, day 7, 28, and day 56.

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. This study will test a medication, CORT108297, which is from a new class of cortisol blockers which have no effect on other hormones. CORT108297 has been shown to have efficacy in preclinical CNS models and was well tolerated and safe in Phase I healthy volunteer studies making it a candidate for further development. Thus, the goal will be to complete a Phase IIa proof of concept trial of CORT108297 to focus on safety and tolerability and obtain pilot efficacy data to inform the design of future clinical trials.

Eligibility criteria: Inclusion Criteria:

* History of US military service
* Capable of reading and understanding English
* Able to provide written informed consent
* Symptoms of PTSD (must score 23 or greater on the CAPS-5 assessment at screening visit)
* Men and pre-menopausal women must agree to use two forms of reliable contraception, one of which is a barrier method.
* Participants who use an SSRI or SNRI medication for PTSD must be on a stable dose for 8 weeks before enrollment.
* Participants who use trazodone for sleep must be on a stable dose.
* Participants who use opiate pain medication must be on a stable dose.
* For participants who are in psychotherapy, treatment must be stable for 6 weeks.

Exclusion Criteria:

* Alcohol use that meets criteria for Alcohol Use Disorder in past 3 months.
* Marijuana or other drug use that meets criteria for Substance Use Disorder in past 3 months.
* Ever diagnosed with: Bipolar Disorder, Schizophrenia, Schizoaffective Disorder, Obsessive-Compulsive Disorder, or Major Depressive Disorder with Psychotic Features
* Experienced any psychologically traumatic event in the past 3 months
* Currently using certain antidepressant medications such as doxepin or tricyclics
* Currently using certain mood stabilizers, such as lithium
* Currently using antipsychotic medication
* High risk for suicide or violent behavior
* Has sleep apnea and not using any treatment, such as CPAP
* Currently using corticosteroid medication (oral or inhaled)
* History of neurological disease
* Angina, congestive heart failure or low blood pressure
* Heart attack in the past 6 months
* Heart block or irregular heartbeat
* Kidney failure, liver failure or pancreatitis
* Severe chronic obstructive pulmonary disease (COPD)
* History of liver disease with lab results on AST or ALT more than 2 times the normal readings
* History of kidney disease with lab results on eGFR less than 60 ml/min
* History of additional risk factors for Torsades de pointes, such as heart failure, low potassium, or family history of a heart rhythm disorder called long QT syndrome
* Use of certain medications that can affect heart rhythm
* Use of certain medications that can interfere with the effects of the study drug
* High blood pressure that is not controlled by medication
* Diabetes that is not well-controlled
* History of certain types of head injuries
* Mild cognitive impairment

Primary outcomes:
measure: Clinician Administered PTSD Scale for DSM-5 (CAPS)
timeFrame: 56 days
measure: Frequency, Intensity, Burden of Side Effects (FIBSER)
timeFrame: 56 days
Secondary outcomes:
measure: Columbia Suicide Severity Rating Scale
timeFrame: 56 days
measure: PTSD Checklist for DSM-5
timeFrame: 56 days
measure: World Health Organization Quality of Life (WHOQOL-BREF)
timeFrame: 56 days
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Tuscaloosa VA Medical Center, Tuscaloosa, AL
state: Alabama
city: San Francisco
country: United States
facility: San Francisco VA Medical Center, San Francisco, CA
state: California
Study officials:
affiliation: San Francisco VA Medical Center, San Francisco, CA
name: Thomas C. Neylan, MD
role: PRINCIPAL_INVESTIGATOR
References: