Neurosteroids in PTSD - Biomarkers to Therapeutics
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Functional Connectivity Between Amygdala-hippocampus Assessed Using fMRI Based Shifted-attention Emotion Appraisal (SEAT) Paradigm.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind, placebo (PBO)-controlled, randomized Phase 2 pilot study
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
DHEA
Subjects will receive a one-time oral dose of DHEA prior to initial brain imaging followed by sustained administration of DHEA for 6 weeks.
干预措施: DHEA (Drug)
结局指标
主要结局
Functional Connectivity Between Amygdala-hippocampus Assessed Using fMRI Based Shifted-attention Emotion Appraisal (SEAT) Paradigm.
时间窗: 6 weeks
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
次要结局
- 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) - Sleep Disturbance Scale(Baseline and 6 weeks)
- Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)(Baseline and 6 weeks)
- Beck-Depression Inventory-II (BDI-II)(Baseline and 6 weeks)
- Patient-Reported Outcomes Measurement Information System (PROMIS) - Pain Intensity Scale(Baseline and 6 weeks)
- PROMIS-Anger Scale(Baseline and 6 weeks)
- Barrat Impulsivity Scale (BIS-11)(Baseline and 6 weeks)
- Connor-Davidson Resilience Scale (CD-RISC)(Baseline and 6 weeks)
- Hamilton Depression Ratings Scale (HAM-D)(Baseline and 6 weeks)
- Patient-Reported Outcomes Measurement Information System (PROMIS) - Depression Scale(Baseline and 6 weeks)
- Patient-Reported Outcomes Measurement Information System (PROMIS) - Anxiety Scale(Baseline and 6 weeks)
- Clinician Global Impression Scale (CGI)(Baseline and 6 weeks)
- Brief Pain Inventory (BPI)(Baseline and 6 weeks)