HYDROCORTISONE for Post-traumatic stress disorder (PTSD)

Inclusion criteria

• {"criterion_text":"- 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)."}
• {"criterion_text":"- Patients must be aged 18-64."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- Progression of patients into substudy B follows based on additional screening criteria, interest and feasibility."}
• {"criterion_text":"- Control group: Healthy, non-trauma exposed control participants (n = 30) will be recruited from the general population in and around Nijmegen."}
• {"criterion_text":"- Control participants only complete assessments from substudy A."}
• {"criterion_text":"- Control participants must be aged 18-64 years."}
• {"criterion_text":"- Inclusion criteria are no history of psychiatric disorders, and no history of childhood maltreatment."}
• {"criterion_text":"- 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."}

Exclusion criteria

• {"criterion_text":"- Current episode of psychotic or manic symptoms."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- A relevant neurological disorder (e.g., stroke, epilepsy, Multiple Sclerosis) or severe physical disorder which is likely to impact assessment procedures or results."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- General learning disability, or known to have intelligence Quotient (IQ) < 80"}
• {"criterion_text":"- Body Mass Index (BMI) of >35."}
• {"criterion_text":"- If relevant, endocrine disorder and/or current or recent endocrine treatment (<1 month ago; for e.g., phechromocytoma, hyperthyroidism, Cushing's syndrome)."}
• {"criterion_text":"- Current or recent regular use of corticosteroids (<1 month ago)."}
• {"criterion_text":"- For women: Pregnancy."}
• {"criterion_text":"- Reports hypersensitivity to hydrocortisone or any of the tablet's auxiliary agents."}
• {"criterion_text":"- (Only for part B) Contraindications for MRI scanning (e.g., pacemaker, implanted metal parts, metal in or around the body, deep brain stimulation, severe claustrophobia). Note: based on the exclusion criteria above, it may be decided by the research team that a participant should onlyparticipate in part A of the study, but will be excluded from part B of the study"}
• {"criterion_text":"- History of childhood maltreatment"}
• {"criterion_text":"- Current or past psychiatric disorder"}
• {"criterion_text":"- Use of psychotropic medication"}
• {"criterion_text":"- Relevant neurological disorder (e.g., stroke, epilepsy, Multiple Sclerosis) or severe physical disorder which is likely to impact assessment procedures or results."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- General learning disability, or known to have intelligence Quotient (IQ) < 80"}
• {"criterion_text":"- Body Mass Index (BMI) of >35."}
• {"criterion_text":"- If relevant, endocrine disorder and/or current or recent endocrine treatment (<1 month ago; for e.g., phechromocytoma, hyperthyroidism, Cushing's syndrome)."}
• {"criterion_text":"- Current or recent regular use of corticosteroids (<1 month ago)."}
• {"criterion_text":"- For women: Pregnancy."}

Primary endpoints

• {"endpoint_text":"- For substudy A, the main study parameters are (1) early life adversity, (2) Hypothalamic-pituitary-adrenal axis functioning, and (3) epigenetic mechanisms.\n- For substudy B, the main study parameter regards retention of the safety memory within the VR contextual fear conditioning environment.","definition_or_measurement_approach":"Substudy A: measurement approach not specified in the primary endpoint text (related measures such as salivary cortisol and epigenetic assays are described elsewhere in the protocol/secondary endpoints).\nSubstudy B: retention of safety memory within the VR contextual fear conditioning environment, operationalised as reductions in the physiological fear response to a conditioned stimulus after extinction (as stated in the study main objective)."}

Secondary endpoints

• {"endpoint_text":"- For substudy A: salivary cortisol response curve to the SECPT (a validated stress test).","definition_or_measurement_approach":"Salivary cortisol response curve measured in response to the SECPT (socially evaluated cold pressor test) as a validated stress-test cortisol time-course."}
• {"endpoint_text":"- For substudy A: treatment response to focused treatment for PTSD.","definition_or_measurement_approach":"Treatment response to trauma-focused therapy; specific instruments or scales not specified in the provided JSON."}
• {"endpoint_text":"- For substudy B: BOLD-fMRI response during fear extinction.","definition_or_measurement_approach":"Measured using BOLD functional MRI during fear extinction tasks."}
• {"endpoint_text":"- For substudy B: BOLD-fMRI general amygdala responsiveness during viewing of emotional faces.","definition_or_measurement_approach":"Measured using BOLD fMRI task-based responses to emotional face stimuli, focusing on amygdala activation."}
• {"endpoint_text":"- For substudy B: Resting state fMRI functional coupling between vmPFC and amygdala.","definition_or_measurement_approach":"Measured using resting-state fMRI connectivity analyses between ventromedial prefrontal cortex (vmPFC) and amygdala."}
• {"endpoint_text":"- For substudy B: Structural MRI (T1-weighted MP-RAGE) and DTI scans.","definition_or_measurement_approach":"Measured using structural MRI (T1-weighted MP-RAGE) and diffusion tensor imaging (DTI) protocols to assess brain structure and connectivity."}

Methods

• Recruitment via collaborating treatment centres (patients recruited before start of their trauma-focused therapy).
• Recruitment independent from treatment centres: participants who declare to have received a PTSD diagnosis by a doctor/specialist and currently experience considerable PTSD symptoms (screened with CAPS-5 to confirm current diagnosis).
• Control participants recruited from the general population in and around Nijmegen, selected to match age, gender and education distributions.

Netherlands

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

28-10-2024

Processing Time Days

4

Number Of Sites

3

Number Of Participants

190

Primary sponsor

Full Name

Stichting Radboud universitair medisch centrum

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands