Targeted glucocorticoid administration to improve safety learning in PTSD patients with HPA axis dysregulatio
- Conditions
- Posttraumatic Stress DisorderTrauma-related Anxiety Disorder10002861
- Registration Number
- NL-OMON52772
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 190
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.
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 only participate 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Substudy A: Main parameters as derived from the patient group are (i) DNA<br /><br>methylation of NR3C1 and allele-specific DNA methylation of FKBP5, (ii) ELA,<br /><br>measured with the *Maltreatment and Abuse Chronology of Exposure Scale* (MACE-<br /><br>X), and (iii) HPA axis dysregulation, operationalised as percentage of cortisol<br /><br>awakening response (CAR) suppression (following the intake of dexamethasone).<br /><br><br /><br>Substudy B: Main parameters reflect the retention of the safety memory during<br /><br>the retention tests, which is operationalised as return of fear indicated by<br /><br>skin conductance response (SCR). Secondary parameters to investigate the same<br /><br>objective regard other measures of autonomic nervous system (ANS) response,<br /><br>that is pupil dilation (PD) and heart rate (HR), as well as subjective shock<br /><br>expectancy ratings. </p><br>
- Secondary Outcome Measures
Name Time Method <p>For substudy A, secondary parameters regard treatment response, and<br /><br>measurements of glucocorticoid signalling in the non-trauma exposed control<br /><br>group.<br /><br>For substudy B, secondary parameters address underlying neural mechanisms of<br /><br>safety learning and (other) group-related differences in brain structure and<br /><br>function, including the effects of hydrocortisone administration on<br /><br>fear-related brain activation patterns. </p><br>