Posttraumatic Stress Disorder (PTSD) MedDRA version: 20.0 Level: LLT Classification code 10036876 Term: Prolonged posttraumatic stress disorder System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Hydrocortison CF
Product Name: Hydrocortison CF
Product Code: RVG 50730
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Ora
Sponsors
Radboudumc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient group: Participants with PTSD (n = 160) will be recruited (1) at collaborating treatment centres, before the start of their trauma-focused therapy treatment, when they have at least a suspected PTSD diagnosis with an indication for trauma-focused therapy, or (2) independently from treatment centres, when they declare to have received a PTSD diagnosis by a doctor or specialist and currently experience considerable PTSD symptoms; these participants will be screened with a PTSD diagnostic interview (CAPS-5) to confirm current PTSD diagnosis (otherwise exclusion).Patients must be aged 18-64. If applicable, the expected waiting time until treatment is sufficient for participation, at least for part A of the study, with minimal overlap with treatment beng allowed (as specified in research protocol). Progression of patients into substudy B follows based on additional screening criteria, interest and feasibility. Control group: Healthy, non-trauma exposed control participants (n = 30) will be recruited from the general population in and around Nijmegen. Control participants only complete assessments from substudy A. Control participants must be aged 18-64 years. Inclusion criteria are no history of psychiatric disorders, and no history of childhood maltreatment. Hence, this group will reflect a healthy, non-trauma exposed control group, Control participants will be selected based on age, gender and education, with the aim to match the distributions of these relevant basic demographic variables to the (expected) distributions of the included patient group. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 190 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patient group: • Current episode of psychotic or manic symptoms. • Daily intake of benzodiazepines, or otherwise irregular intake of benzodiazepines (“when needed”) but unable to withhold intake from the day prior to each test session until the end of the each test session. An exception is made for low doses of short-acting benzodiazepines that are prescribed for insomnia (i.e. as sleep medication). • A relevant neurological disorder (e.g., stroke, epilepsy, Multiple Sclerosis) or severe physical disorder which is likely to impact assessment procedures or results. • Reports to be unable or unwilling to withhold recreational drug use and limit alcohol use from the day prior to each test session until the end of the each test session. • General learning disability, or known to have intelligence Quotient (IQ) 35. • If relevant, endocrine disorder and/or current or recent endocrine treatment (35. • If relevant, endocrine disorder and/or current or recent endocrine treatment (<1 month ago; for e.g., phechromocytoma, hyperthyroidism, Cushing’s syndrome). • Current or recent regular use of corticosteroids (<1 month ago). • For women: Pregnancy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Substudy A: To investigate, within a sample of PTSD patients, the associations between history of early life adversity (ELA), epigenetic mechanisms, and HPA axis dysregulation. Substudy B: To investigate whether the subgroup of PTSD patients with HPA axis dysregulation particularly benefits from glucocorticoid augmentation (hydrocortisone administration) of safety learning, as indicated by greater reductions in the physiological fear response to a conditioned stimulus after extinction.;Secondary Objective: Substudy A: •Replicate findings of HPA axis dysregulation in PTSD patients relative to a control group •Investigate whether functional markers of HPA axis activity and glucocorticoid signalling are associated with treatment response Substudy B: •Investigate whether patients with HPA axis dysregulation, under normal circumstances, show impairments in safety learning •Investigate whether impairments in safety learning for those with HPA axis dysregulation versus those without HPA axis dysregulation are accompanied by differences in neural activity during safety learning •Investigate if hydrocortisone administration normalises the brain activity that underlies impairments in safety learning •Investigate differences in brain structure and connectivity based on HPA axis dysregulation •Investigate differences in amygdala reactivity to biologically salient stimuli (emotional faces) based on medication effects and HPA axis dysregulation ;Primary end point(s): For substudy A, the main study parameters are: •ELA; operationalised as severity score (range 0-100) on the 75-item “Maltreatment and Abuse Chronology of Exposure” (MACE-X) (73). This scale shows acceptable psychometric properties and correlates with other commonly used trauma questionnaires, however it showed increased explained variance for psychiatric symptom scores. The scale consists of 52 items that assess exposure to ten types of childhood trauma (emotional neglect, non-verbal emotional ab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Substudy A: Secondary study parameters are assessed in order to investigate secondary objectives. For substudy A, this includes salivary cortisol response curve to the SECPT ( a validated stress test) and treatment response to trauma-focused treatment for PTSD. Treatment response is operationalised as improvement in the total score (range 0-80) on “PTSD Checklist for DSM-5” (PCL-5). These questionnaires are completed by patients as part of the Routine Outcome Measure-ment (ROM) programme at the treatment centre and at follow-up. Substudy B: Secondary study parameters corresponding to secondary objectives include the following MRI endpoints: • BOLD-fMRI response during fear extinction • BOLD-fMRI general amygdala responsiveness during viewing of emotional faces. • Resting state fMRI functional coupling between vmPFC and amygdala • Structural MRI (T1-weighted MP-RAGE) and DTI scans, which yield integrity measures of brain structure and structural connectivity ;Timepoint(s) of evaluation of this end point: For PTSD symptoms (treatment success): if possible all ROM data and the follow-up measurement | — |
Countries
Netherlands
Contacts
Public ContactDept of Cognitive Neuroscience
Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre
Outcome results
None listed