Cortisol in personalized treatment for posttraumatic stress disorder (PTSD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud universitair medisch centrum

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

28 Oct 2024 → ongoing

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516427-13-00

EudraCT number

2020-000712-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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 objectives 1

1. 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

Conditions and MedDRA coding

Posttraumatic Stress Disorder (PTSD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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.

Exclusion criteria 1

1. 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) < 80 • Body Mass Index (BMI) of >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. • Reports hypersensitivity to hydrocortisone or any of the tablet's auxiliary agents. • (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 Control group: • History of childhood maltreatment • Current or past psychiatric disorder • Use of psychotropic medication • 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) < 80 • Body Mass Index (BMI) of >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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. For substudy A, the main study parameters are (1) early life adversity, (2) Hypothalamic-pituitary-adrenal axis functioning, and (3) epigenetic mechanisms. For substudy B, the main study parameter regards retention of the safety memory within the VR contextual fear conditioning environment.

Secondary endpoints 1

1. For substudy A, this includes (1) salivary cortisol response curve to the SECPT ( a validated stress test) and (2) treatment response to focused treatment for PTSD. For substudy B, this includes the following MRI endpoints (1) BOLD-fMRI response during fear extinction, (2) BOLD-fMRI general amygdala responsiveness during viewing of emotional faces (3) Resting state fMRI functional coupling between vmPFC and amygdala(4) Structural MRI (T1-weighted MP-RAGE) and DTI scans.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud universitair medisch centrum

Sponsor organisation

Stichting Radboud universitair medisch centrum

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Erno Hermans

Public contact point

Organisation

Stichting Radboud universitair medisch centrum

Contact name

Erno Hermans

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications