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Posttraumatic Stress DisorderPhase 2NCT03491007

Neurosteroids in PTSD - Biomarkers to Therapeutics

A Phase 2 study testing DHEA in people with Posttraumatic Stress Disorder, run by VA Office of Research and Development at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Posttraumatic Stress Disorder
What is being tested?
DHEA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
5 participants
Where
1 siteUnited States
Study dates
8 Jul 2019to 16 Nov 2020
Phase
Phase 2
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Durham VA Medical Center, Durham, NC

    Durham, North Carolina, 27705

Other trials in United States

About this study

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.

Read the detailed description

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

The investigators' first objective is POC target engagement to evaluate a one-time adjunctive oral dose of DHEA (400 mg) relative to PBO on the neuronal circuity of fear-anxiety-emotion connectivity. This will be achieved by comparing pre- to post-treatment changes in amygdala-hippocampal functional connectivity to DHEA and PBO during fMRI activation. The investigators hypothesize that compared with PBO, DHEA will increase task-associated fMRI functional connectivity between the amygdala and hippocampus (primary outcome).

The second objective is to determine if an 8-week treatment with adjunctive DHEA is superior to PBO in reducing symptoms of PTSD (CAPS-5) and depression (BDI) in OEF/OIF/OND Veterans, and enhancing resilience (CD-RISC). The investigators hypothesize that 400mg DHEA will result in reduced PTSD and depression symptom severity relative to PBO, as determined by a pre- to post-treatment decrease in CAPS-5 and BDI scores, respectively, with enhancement in resilience scores using the CD-RISC at 6-weeks.

The third objective is to evaluate the impact of DHEA relative to PBO on serum neurosteroid levels in OEF/OIF/OND Veterans with PTSD. The investigators hypothesize that DHEA will result in a statistically-significant increase in serum neurosteroid levels (DHEA, DHEAS, androsterone) relative to PBO, as determined by pre- to post-treatment reductions in PTSD symptoms severity. This association will be evaluated by correlating neurosteroid levels with PTSD, depression, and resilience scores over 6 weeks of treatment.

The exploratory objective is to determine preliminary evidence for an association of fMRI and myelin integrity measures of fear-anxiety-emotion circuits with serum neurosteroid levels and treatment response to DHEA. Changes in myelin integrity following DHEA treatment will be evaluated using novel susceptibility diffusion imaging [STI]), as DHEA impacts myelination in preclinical rodent models. The investigators will also determine if serum neurosteroid levels are correlated with myelin integrity on STI. The investigators hypothesize that fMRI and myelin integrity of fear-anxiety circuits will correlate with serum neurosteroids and treatment response.

Being tested
DHEA
Keywords
PTSD, DHEA
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.

  • DHEADrug

    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).

Study groups in NCT03491007
Study groupRoleWhat they receive
PlaceboNo interventionSubjects will receive a one-time oral dose of PBO prior to initial brain imaging followed by sustained administration of PBO for 6 weeks.
DHEAPlacebo comparatorSubjects will receive a one-time oral dose of DHEA prior to initial brain imaging followed by sustained administration of DHEA for 6 weeks.
Receives: Drug: DHEA

What is being measured

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

  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

    Measured: 6 weeks

Secondary outcomes (14)
  1. Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

    The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to make a diagnosis of PTSD and assess PTSD symptoms. It assesses the intensity and frequency of PTSD symptoms. Change in total CAPS-5 score from baseline to 6 weeks. Scores range from 0-80; higher score indicates greater severity.

    Measured: Baseline and 6 weeks

  2. Beck-Depression Inventory-II (BDI-II)

    The BDI-II is a 21-item self-report inventory of depression symptoms. The minimum and maximum values for the BDI-II are (0-63). Change in total BDI-II score from baseline to 6 weeks. Higher score indicates greater severity.

    Measured: Baseline and 6 weeks

  3. Hamilton Anxiety Rating Scale (HAM-A)

    The HAM-A is clinician-rated interview that measures presence of anxiety-related symptoms in 14 areas. Total score ranges from 0 to 56. Higher score indicates greater anxiety. Change in total HAM-A score from baseline to 6 weeks

    Measured: Baseline and 6 weeks

  4. Symptom Checklist-90-Revised (SCL-90-R)

    Change in total SCL-90-R score (range: 90 to 450; higher score indicates greater severity) from baseline to 6 weeks. This scale assesses somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism.

    Measured: Baseline and 6 weeks

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

    PROMIS Pain Intensity is a three item scale measuring the severity of pain using a five-point Likert-type scale (i.e., no pain=1, mild=2, moderate=3, severe=4, very severe=5).Change in total PROMIS Pain Intensity Scale score (range: 3 to 15) from baseline to 6 weeks. Higher score indicates greater severity.

    Measured: Baseline and 6 weeks

  6. Patient-Reported Outcomes Measurement Information System (PROMIS) - Sleep Disturbance Scale

    The 8-item PROMIS Sleep Disturbance measures sleep disturbance with each item on the measure rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8-40. Change in total PROMIS-Sleep Disturbance score from baseline to 6 weeks. Higher score indicates greater severity.

    Measured: Baseline and 6 weeks

  7. PROMIS-Anger Scale

    The PROMIS-Anger Scale is an 8-item scale that assesses anger. Scores range from 5 to 25, with higher scores indicating greater anger severity. Change in total PROMIS-Anger score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  8. Barrat Impulsivity Scale (BIS-11)

    The BIS-11 is a 30 item questionnaire to measure impulsiveness. Items are answered on a 4-point scale. Total scores range from 30-120 with a higher summed score indicating higher impulsivity. Change in total BIS-11 score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  9. Connor-Davidson Resilience Scale (CD-RISC)

    The CD-RISC scale assesses resiliency in individuals. There are 25 items in the survey, each item is scored from 0-4, and the total ranges from 0-100. Higher scores indicate greater resilience. Change in total CD-RISC score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  10. Hamilton Depression Ratings Scale (HAM-D)

    The HAM-D is a standardized, clinician-administered rating scale; assesses 17 items characteristically associated with major depression. Total scores range from 0-50. Higher score indicates greater severity. Change in total HAM-D score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  11. Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Scale

    PROMIS-Depression Scale is a self-reported scale of depressive symptoms Each item is scored 1-5 (1 = Never; 5 = Always). Total ranges are 8 to 40. Higher score indicates greater severity. Change in total PROMIS Depression score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  12. Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety Scale

    The PROMIS-Anxiety Scale is a self-report of anxiety symptoms. Each item is scored 1-5 (1 = Never; 5 = Always). Total score ranges from 8 to 40. Higher score indicates greater severity. Change in total PROMIS Anxiety score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  13. Clinician Global Impression Scale (CGI)

    The CGI scale will be used to rate improvement in the subject's condition. Total score range of 0-30. Higher scores indicates greater severity. Change in total CGI score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

  14. Brief Pain Inventory (BPI)

    The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning. Total range of 0-110. Higher score indicates greater severity. Change in total BPI score from baseline to 6 weeks.

    Measured: Baseline and 6 weeks

Timeline

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

  1. First posted6 Apr 2018
  2. Study start8 Jul 2019
  3. Primary completion16 Nov 2020
  4. Study completion16 Nov 2020

Why it stopped: PI obtained outside employment that was not compatible with this award

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03491007
Sponsor's protocol ID
MHBB-021-17S
Other IDs
1IK2CX001397-01A2
Status last verified
May 2023
First submitted
30 Mar 2018
Last updated
6 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DHEA in people with Posttraumatic Stress Disorder, run by VA Office of Research and Development at 1 site 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 11 inclusion and 14 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: stopped early, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2023). 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?

Functional Connectivity Between Amygdala-hippocampus Assessed Using fMRI Based Shifted-attention Emotion Appraisal (SEAT) Paradigm. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 6 May 2023.

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