Neurosteroids in PTSD - Biomarkers to Therapeutics

NCT03491007 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MHBB-021-17S1IK2CX001397-01A2
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to determine if a study medication called Dehydroepiandrosterone (DHEA) helps to reduce PTSD symptoms in OEF/OIF/OND Veterans. In addition to finding out if DHEA is effective for treating PTSD symptoms, this research seeks to determine if DHEA is effective in treating other symptoms, such as depression and anxiety. Depression and anxiety are symptoms that are frequently present in Veterans who are experiencing PTSD. Another purpose of this research is to takes pictures of the brain using magnetic resonance imaging (MRI) and blood levels of various small molecules including neurosteroids and also proteins, which may be affected by the study drug and/or related to symptoms in Veterans with PTSD. This study seeks to determine if DHEA is changed to other compounds after it is taken by mouth and the safety and effectiveness of DHEA in Veterans with PTSD. This is an "add-on" study and Veterans enrolled in the study will continue to take all of their current medications without any changes (also called "usual care"), and DHEA or a sugar pill (also called a "placebo") will then be added to their current medication regimen.

Conditions

Posttraumatic Stress Disorder

Keywords

PTSD; DHEA

Outcome Measures

Primary Outcomes (1)

• Functional Connectivity Between Amygdala-hippocampus Assessed Using fMRI Based Shifted-attention Emotion Appraisal (SEAT) Paradigm.

  The Shifted-Attention Emotion Appraisal (SEAT) Paradigm will present compound stimuli that include both emotional faces (e.g. sad, happy, angry) and neutral scenes. In three different conditions, participants are asked to respond to three different questions: (1) 'Gender'; (2) 'Inside/Outside'; or (3) 'Like/Dislike'. This allows multiple components of cognition to be probed including (1) implicit emotional processing, (2) attentional modulation, and (3) cognitive modulation of emotion. Item-specific memory will be tested first using yes/no recognition judgments. The conjunctive memory test will require participants to make "match" (previously viewed faces and buildings presented in a combinations seen during encoding) or "mismatch" (items in combinations not previously seen together) judgments. Change in SEAT paradigm (Z score) from baseline to 6 weeks

  6 weeks

Secondary Outcomes (14)

• Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

  Baseline and 6 weeks

• Beck-Depression Inventory-II (BDI-II)

  Baseline and 6 weeks

• Hamilton Anxiety Rating Scale (HAM-A)

  Baseline and 6 weeks

• Symptom Checklist-90-Revised (SCL-90-R)

  Baseline and 6 weeks

• Patient-Reported Outcomes Measurement Information System (PROMIS) - Pain Intensity Scale

  Baseline and 6 weeks

Other Outcomes (4)

• Serum DHEA

  6 weeks

• Myelin Integrity Susceptibility Tensor Imaging (STI)

  6 weeks

• Serum DHEAS

  6 weeks

Study Arms (2)

Placebo

NO INTERVENTION

Subjects will receive a one-time oral dose of PBO prior to initial brain imaging followed by sustained administration of PBO for 6 weeks.

DHEA

PLACEBO COMPARATOR

Subjects will receive a one-time oral dose of DHEA prior to initial brain imaging followed by sustained administration of DHEA for 6 weeks.

Drug: DHEA

Interventions

DHEA DRUG

Subjects will be randomized to receive a one-time oral dose of DHEA (400mg) or PBO and sustained administration of the study drug for 6 weeks. There will be a 2 week placebo lead-in period \[all participants\], followed by subjects continuing in the randomization block of DHEA or placebo for 6 weeks following acute administration).

DHEA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• OEF/OIF/OND era Veterans
• PTSD diagnosis (CAPS-5 score 33).
• Negative pregnancy test if female.
• Sexually active subjects are required to use a medically acceptable form of birth control if they are of childbearing potential and could become pregnant during the study.
• A medically acceptable form of birth control includes non-hormonal intrauterine devices, surgical sterilization, or double barrier methods (e.g., diaphragm with contraceptive jelly, condom with contraceptive foam, cervical caps with contraceptive jelly).
• Sexual abstinence with agreement to continue abstinence or to use a medically acceptable method of contraception should sexual activity occur is permissible.
• Female participants must have had a normal mammogram within the last year (if older than 40)
• Female participants must have had a normal pelvic exam within the last year
• No change in medications less than 4 weeks before baseline assessment
• No anticipated need to alter medications for PTSD for the 6-week study duration (as determined by study physician's review of records and/or discussion with prescribing physician).
• Ability to fully participate in the informed consent process

You may not qualify if:

• Unstable medical or neurological illness, including seizures, renal impairment or CVA and inability to participate in neuroimaging (fMRI).
• Use of oral contraceptives or other hormonal supplements, as it is unclear if DHEA metabolism to other neurosteroids such as estradiol may potentially impact contraceptive efficacy.
• Significant suicidal or homicidal ideation.
• Current DSM-5 diagnosis of bipolar disorder, schizophrenia, or other psychotic disorder (including major depression with psychotic features), or cognitive disorder due to a general medical condition.
• Female patients who are pregnant or breast-feeding.
• Known allergy to study medication.
• History of moderate or severe TBI.
• Substance dependence within past three months, per DSM-5 criteria (excluding caffeine and nicotine).
• Abnormal prostate specific antigen (PSA; \>2.5ng/ml in males age 49 or less; \>4ng/ml in males age 50 or greater) or history of prostate cancer, breast cancer, or uterine cancer.
• A family history of prostate, breast or endometrial cancer in a first-degree relative.
• Presence of any factors/conditions, medical or non-medical, that may interfere with conduction of study assessments in the judgment of the study team.
• Serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition or psychiatric conditions or behaviors that would compromise participation and/or likely to lead to worsening of symptoms during the course of the study in the opinion of study physician and research team.
• Are non-ambulatory or require the use of crutches or a walker.
• Taking Narcotic medications or benzodiazepines for any reason.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Dehydroepiandrosterone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Results Point of Contact

• Title: Susan O'Loughlin
• Organization: Durham VA Healthcare Center

susan.o'loughlin@va.gov

919-286-0411

Study Officials

• Steven Szabo, MD PhD

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, placebo (PBO)-controlled, randomized Phase 2 pilot study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is a parallel-group, double-blind, placebo (PBO)-controlled, randomized Phase 2 pilot study using adjunctive dehydroxyepiandrosterone \[DHEA (400 mg)\] will be evaluated to establish Proof of Concept (POC) for this agent in Veterans with PTSD.

Study Record Dates

• First Submitted: March 30, 2018
• First Posted: April 6, 2018
• Study Start: July 8, 2019
• Primary Completion: November 16, 2020
• Study Completion: November 16, 2020
• Last Updated: May 6, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)