In this functional Magnetic Resonance Imaging (fMRI) study, the primary objective is to examine the acute effects of intranasal OT administration on emotional- and reward-related brain processes in PTSD patients compared to traumatized healthy…
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Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main outcome measures of this study are the acute effects of intranasal OT
administration on emotional- and reward related brain processes in men and
women diagnosed with PTSD compared to traumatized healthy controls.
Emotional and reward-related brain processes will be acquired on a 3T Philips
Achieva MR system located at the Spinoza Center. To measure the effects of OT
administration on neural BOLD response, echo-planar images sensitive to
BOLD-contrast will be obtained from each subject during three tasks:
1. Emotional face matching task, in which three faces of the same emotion
(either happy, fearful or neutral) are presented and the participant is
required to match the gender of the first face with those of the other faces.
The face matching condition will be compare with a sensorimotor control
condition.
2. Reward task, in which sensitivity to monetary and social reward- and loss
anticipation and consumption is measured. This will be compared to a neutral
condition in which no reward or loss is anticipated or consumed.
3. Emotion regulation task, in which the participant is asked to either look at
pictures of negative and neutral scenes or to reappraise negative scenes. BOLD
contrast images will be calculated for the emotion regulation versus the
passive viewing condition.
During task execution, psychobiological measures such as reaction times and
accuracy on the face-matching and reward tasks, heart rate and heart rate
variability will be assessed.
In addition, a resting-state scan, a high-resolution T1-weighted anatomical
scan and Diffusion Tensor Weighted Images (DTI) will be collected.
Secondary outcome
1. Gender differences in the effects of intranasal OT administration on
functional (task-specific) brain activation between PTSD patients and
traumatized healthy controls will be investigated. Salivary levels of estrogen
and testosterone will be measured during both fMRI sessions to assess the role
of endogenous steroid hormone levels on the main study outcome.
2. Answers to various questionnaires will be used to examine potential
associations between the main study outcome and representations of attachment
style, social support and history of (childhood) trauma and life events.
3. (Epi)genetic variation will be assessed to investigate potential
associations with the main study outcome. In addition, information on genetic
variants of participants will be used in a meta-analysis on genes associated
with PTSD, carried out by the Psychiatrics Genetics Consortium. Participants
will be asked for additional consent to share the data within this
international collaboration.
4. Individual variation in HPA axis functioning (i.e. cortisol levels assessed
in hair) will be assessed to investigate potential associations with the main
study outcome.
Background summary
About 80% of people experience a traumatic event during their life. Of these
10% develop a posttraumatic stress disorder (PTSD), thus leading to an overall
estimated lifetime prevalence of PTSD of 8% in the general population. Because
of this high prevalence, but also its excess disability, negative impact on
quality of life and somatic consequences, the public health impact of PTSD is
enormous. Regarding treatment of PTDS, a substantial part of patients drop out
of treatment, remain symptomatic or relapse after initial response to
treatment, making novel strategies to boost treatment response necessary.
A promising candidate to improve treatment response in PTSD is the neuropeptide
oxytocin (OT). OT is involved in several processes disrupted in PTSD, i.e. the
fear response, social interaction and reward. In addition, OT is implicated in
the pathophysiology of psychiatric disorders involving disturbed stress
regulation as well as disrupted attachment and/or social deficits. Therefore,
investigating the role of OT administration on emotional and reward-related
processes in the brain may lead to novel strategies to improve treatment for
PTSD. OT is a safe drug normally used for lactation deficiency and is easy to
administer as a nasal spray.
Study objective
In this functional Magnetic Resonance Imaging (fMRI) study, the primary
objective is to examine the acute effects of intranasal OT administration on
emotional- and reward-related brain processes in PTSD patients compared to
traumatized healthy controls.
In the baseline (placebo) condition, we expect PTSD patients to show higher
neural sensitivity to fear-inducing visual stimuli and lower neural sensitivity
to (social) reward compared to traumatized healthy controls. In addition, we
hypothesize to find increased functional connectivity between the amygdala and
brainstem regions after placebo administration in PTSD patients compared to
traumatized controls.
We expect that OT administration in PTSD patients and controls will dampen
amygdala responsivity towards threatening stimuli. Furthermore, we expect to
find increased reward sensitivity, i.e. increased activity in reward-related
brain areas (i.e. nucleus accumbens and subgenual prefrontal cortex) and
altered interregional communication within fear-and reward-related neural
networks after OT administration in PTSD patients and controls.
We expect to see a group by treatment interaction effect, such that the neural
effects of OT treatment will differ in magnitude between PTSD patients and
controls.
Study design
In this double-blind randomized controlled within-subjects study, a comparison
is made between PTSD patients and traumatized healthy controls. In a
double-blinded way, participants will be randomized to medication order. Half
of the participants will receive intranasal OT during the first and placebo
during the second fMRI session. The other half of the participants will receive
placebo during the first and intranasal OT during the second fMRI session.
We will assess the effects of one dose of intranasal OT (40 IU; 5 puffs of 4 IU
per nostril) compared to placebo (saline) on emotional -and reward-related
brain processes. OT is a safe drug to administer (Macdonald et al., 2011),
registered in the Netherlands and commonly used in women who have difficulties
breastfeeding. The dose of 40 IU has been used safely in a study with
psychiatric patients.
Study burden and risks
Since we will conduct a study in psychiatric patients (i.e. PTSS patients), the
risk classification associated with this study is *minimal excess of negligible
risk*. OT is a save drug, except during pregnancy. Therefore, female
participants with childbearing potential must have a negative pregnancy test
before commencing study participation. Functional magnetic resonance imaging
(fMRI) is not harmful for the participants.
Meibergdreef 5
Amsterdam 1105 AZ
NL
Meibergdreef 5
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
* Age 18 * 65 years
* Capable to read and comprehend the Dutch language
* Eligibility for MRI (i.e. no metals, pacemakers or claustrophobia)
* Exposed to a potentially traumatic event, according to PTSD A1 criterion in the DSM-IV (minimal 1 month ago), quantified as a score of 1 or higher on the Life Events Checklist (LEC).
PTSD patients:
* Current PTSD diagnosis
* CAPS score * 45
Traumatized healthy controls:
* CAPS-score < 15
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
* 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), ß-adrenergic receptor-blocking agents, systemic glucocorticoids and psychopharmacological medication.
* Sensitivity or allergy for OT or its components (e.g. methylhydroxybenzoate and propylhydroxybenzoate)
* Female participants: pregnancy and breast feeding (NB. Female participants with childbearing potential must have a negative pregnancy test).
Traumatized healthy controls only:
* (lifetime history of) PTSD diagnosis, major depressive disorder.
* Current DSM-IV axis 1 disorder
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 | EUCTR2012-001288-58-NL |
| CCMO | NL40122.018.12 |