Primary aim:In recently traumatized individuals (at the latest on day ten post trauma exposure) with a high initial level of distress, we aim to assess the effectiveness of intranasal OT in preventing symptoms of PTSD at one months post intervention…
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study outcome is the difference in PTSD symptoms severity (CAPS
scores) between the two trial arms (i.e. OT versus placebo) at one month post
intervention follow-up.
The main study outcomes for the fMRI substudy are differences in amygdala
activation to emotional faces and differences in brain functional connectivity
after stress induction between the two study conditions.
Secondary outcome
* Differences between intervention groups in depression and general anxiety
symptoms, neuroendocrine / psychophysiological measures, perceived social
support and psychological functioning between the two groups after one week of
OT treatments, and one and a half, three and six months post trauma exposure.
* Differences between intervention groups in PTSD symptoms severity (CAPS
scores) between the two trial arms (i.e. OT versus placebo) at three and six
months post trauma follow-up.
* Potential associations between the main study outcome and gender, genetic
variation, perceived social support, representations of attachment style,
coping style, subjective health complaints, quality of life, trauma type,
history of (childhood) trauma and life events.
fMRI substudy only:
* Differences in salivary cortisol, DHEAS, and OT reactivity after intranasal
OT between the two study groups.
* Differences in the role of endogenous steroid hormone levels (i.e. estrogen,
progesterone and testosterone) in the effect of intranasal OT on neural
(stress) reactivity between the two groups.
* Potential associations between the main study outcome and gender, genetic
variation, perceived social support, representations of attachment style,
coping style, subjective health complaints, quality of life, trauma type,
history of (childhood) trauma and life events.
Background summary
Eighty per cent of the general population experiences a traumatic event in
their life span, of which 10% will develop post traumatic stress disorder
(PTSD). It is widely acknowledged that PTSD has a major influence on the health
and economic situation of patients, their relatives, and society in general.
However, no effective early interventions in the acute phase after
traumatization exist that can decrease the subsequent risk for PTSD
development.
Social support is one of the most powerful protective influences against PTSD.
However, little is known about the neurobiology behind this mechanism and no
proven effective interventions are available that stimulate social support
seeking behavior.
An important role in the mechanism behind the positive effects of social
support is attributed to the neuropeptide oxytocin (OT), a hormone that is
synthesized in the brain and released during positive social interactions and
is associated with pair bonding, empathy, and trust. It is believed that OT
treatment results in in increased susceptibility for (the positive effects of)
experiencing social support.
Furthermore, OT is synthesized and released during stressful events. This
consequently promotes stress regulation at the level of both the neuroendocrine
and autonomic stress system. Studies using intranasal OT treatments in humans
have demonstrated that OT influences brain activity patterns and stress
responses during a (stress) task. This is relevant for PTSD research, in which
it is currently believed that inadequate and prolonged stress responses are an
underlying mechanism in PTSD development.
Thus, OT treatment could benefit individuals that are at risk of developing
PTSD in several ways: by influencing the neuroendocrine and autonomic stress
response and by enhancing susceptibility for social support.
fMRI substudy: Animal and human research show that OT administration influences
brain areas involved in stress regulation. Handholding has also been shown to
reduce neural reactivity to threat.
Study objective
Primary aim:
In recently traumatized individuals (at the latest on day ten post trauma
exposure) with a high initial level of distress, we aim to assess the
effectiveness of intranasal OT in preventing symptoms of PTSD at one months
post intervention follow-up.
In an fMRI-eligible subgroup of the participants, we aim to investigate the
acute effects of intranasal OT on brain activation and connectivity patterns.
Secondary aims include to:
* Investigate the effects of OT on depression and general anxiety symptoms,
neuroendocrine and psychophysiological measures, perceived social support, and
psychological functioning after one week of intranasal treatments, and at one
and a half, three and six months post trauma follow-up;
* Investigate the effectiveness of intranasal OT administration in preventing
symptoms of PTSD at 3 and 6 months,post trauma follow-up compared to intranasal
placebo treatment.
* Examine potential associations between the main study outcome and gender,
genetic variation, subjective measures of social support, representations of
attachment style, coping style, subjective health complaints, quality of life,
trauma type and history of (childhood) trauma and life events.
fMRI substudy only:
* To study the effects of intranasal OT on salivary cortisol, DHEAS, and OT
reactivity.
* To assess the role of endogenous steroid hormone levels (i.e. estrogen,
progesterone and testosterone) in the effect of OT on neural (stress)
reactivity.
* Examine potential associations between the main study outcome and gender,
genetic variation, subjective measures of social support, representations of
attachment style, coping style, subjective health complaints, quality of life,
trauma type and history of (childhood) trauma and life events.
Study design
We propose to conduct a double-blind randomized placebo controlled trial on the
effectiveness of oxytocin versus placebo treatments on the development of
trauma related psychopathology in recently traumatized individuals at risk for
developing PTSD.
At the latest on day ten after trauma exposure participants (after written
informed consent) will be blindly randomized to the oxytocin or placebo
treatment condition.
This is a cross-sectional double-blind (for OT administration) randomized
controlled study to assess the acute effects of our interventions on brain
activation.
Intervention
Half of the participants will self-administer a total of 15 doses of intranasal
oxytocin (40 IU, 5 sprays per nostril) or placebo (5 sprays per nostril). The
first treatment will be at the AMC. 14 treatments will occur on 7 consecutive
days in the home environment. The total duration of intranasal treatments is 8
days.
In case a participant only wants to participate in the fMRI study, he/she will
only apply a single dose of intranasal treatment.
Study burden and risks
The burdens and risks associated with participation with this study are
minimal. Oxytocin is safe to administer to non-pregnant individuals (Females
with a child-bearing potential should have a negative pregnancy test).
Undergoing an fMRI scan is not harmful.
Meibergdreef 5
Amsterdam 1105 AZ
NL
Meibergdreef 5
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
* Presentation at the Trauma Room or Emergency Department after a potential traumatic event, according to PTSD A1 criterion in the DSM-IV (either as a patient or direct witness);
* Trauma Screening Questionnaire (TSQ) <=/> 5 and/or Peritraumatic Distress Inventory (PDI ) <=/> 17 preferably between 24 and 72 hours after trauma exposure (in case of contacting difficulties up to 7 days after trauma);
* Age 18 * 65 years;
* Capable to read and comprehend either the Dutch or English language;
Exclusion criteria
* Any severe or chronic systemic disease;
* Current psychotic, bipolar, substance-related, severe personality disorder, or mental retardation;
* Current severe depressive disorder;
* Prominent current suicidal risk or homicidal ideation;
* Severe cognitive impairment or a history of organic mental disorder;
* Evidence of PTSD or depression immediately prior to the index trauma;
* History of neurological disorders (e.g., traumatic brain injury, seizure history;
* Reports of ongoing traumatization (e.g., in case of partner violence as index adult trauma;
* Evidence of clinically significant and unstable medical conditions in which OT administration is contra-indicative such as cardiovascular, gastro-intestinal, pulmonary, severe renal, endocrine or hematological disorders, glaucoma, history of epilepsy, or a stroke or myocardial infarction within the past year;
* Use of certain medication: prostaglandins, certain anti-migraine medications (ergot alkaloids), bèta-adrenergic receptor-blocking agents, and systemic glucocorticoids;
* Sensitivity or allergy for OT or its components (e.g., methylhydroxybenzoate and propylhydroxybenzoate);
* Impaired consciousness, or amnesia or confusion (due to for example head injury) (objectified by Glasgow Coma Scale lower than 13 at time of inclusion)
* Female participants: pregnancy and breast feeding (NB. Female participants with childbearing potential must have a negative pregnancy test);
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-004177-83-NL |
| CCMO | NL37202.018.11 |