Neural and Pharmacological Correlates of Intrusions in Patients With Posttraumatic Stress Disorder

NCT ID: NCT01108133

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-03-31

Brief Summary

There is evidence that glucocorticoids have an impact on intrusive memories in patients with posttraumatic stress disorder (PTSD). Hydrocortisone impairs intrusive memory retrieval whereas dexamethasone should strengthen intrusions in PTSD. We, the investigators, want to investigate (1) the effect of these two glucocorticoids on traumatic memories and (2) assess the neural correlates using the script-driven imagery paradigm in the functional magnetic resonance imaging (fMRI) scanner. We hypothesize that intrusive memories are less intensive under hydrocortisone-administration and more intense under dexamethasone-administration comparing both to a placebo-condition. Regarding the neural activation pattern we expect higher activation in the hydrocortisone condition in the amygdala, the hippocampus and the medial prefrontal cortex compared to the placebo-condition and less activation in the dexamethasone-condition compared to the placebo-condition.

Detailed Description

There is evidence that glucocorticoids have an impact on intrusive memories in patients with posttraumatic stress disorder (PTSD). Hydrocortisone impairs intrusive memory retrieval whereas dexamethasone should strengthen intrusions in PTSD. We, the investigators, want to investigate (1) the effect of these two glucocorticoids on traumatic memories and (2) assess the neural correlates using the script-driven imagery paradigm in the functional magnetic resonance imaging (fMRI) scanner. Therefore an individual trauma-and an individual neutral -script is assessed from each participant, recorded and replayed during fMRI-scanning. We hypothesize that intrusive memories are less intense under hydrocortisone-administration and more intense under dexamethasone-administration comparing both to a placebo-condition. Regarding the neural activation pattern we expect higher activation in the hydrocortisone condition in the amygdala, the hippocampus and the medial prefrontal cortex compared to the placebo-condition and less activation in the dexamethasone-condition compared to the placebo-condition.

Conditions

Posttraumatic Stress Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Hydrocortisone, fMRI, Intrusions

10 mg Hydrocortisone are administered one hour before the fMRI experiment. We use the script-driven imagery paradigm to induce intrusive memories during fMRI scanning.

Group Type: EXPERIMENTAL

10 mg HydrocortisoneHöchst

Intervention Type: DRUG

10 mg Hydrocortisone Höchst are administered one hour before fMRI scanning

Dexamethasone, fMRI, Intrusions

2 mg Dexamethasone are administered at 10 pm the day before the fMRI experiment. (DEX-Test). We use the script-driven imaging paradigm to induce intrusive memories during fMRI-scanning.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

2 mg Dexamethasone are administered at 10 pm the day before the fMRI experiment.

Placebo, fMRI, Intrusions

Placebo is administered one hour before the fMRI experiment. We use the script-driven imaging paradigm to induce intrusive memories during fMRI-scanning in patients with posttraumatic stress disorder.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo

Interventions

10 mg HydrocortisoneHöchst

10 mg Hydrocortisone Höchst are administered one hour before fMRI scanning

Intervention Type: DRUG

Dexamethasone

2 mg Dexamethasone are administered at 10 pm the day before the fMRI experiment.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

HydrocortisoneHöchst

Eligibility Criteria

Inclusion Criteria

• Age: 18-45
• Female
• Posttraumatic Stress Disorder assessed by the Structured Clinical Interview (SKID-I)
• Intrusive memories (Impact of Events Scale - Revised [IES-R] intrusion scale > 7)

Exclusion Criteria

• • Lifetime diagnosis schizophrenia according to Diagnostic and Statistical Manual, Fourth Edition (DSM-IV)

• Mental retardation
• Body mass index < 16.5
• Current drug and alcohol abuse and addiction
• Life-threatening self-injurious behavior in the last 4 months
• Suicide attempt with the strong intention to die in the last 4 months.
• Following diseases in anamnesis: stomach ulcera or intestinal ulcera, pancreatitis, corticoid-induced psychosis, severe osteoporosis, severe hyper-tension, heart failure, myasthenia gravis, asthma bronchiale, glaucoma, cataract, diabetes mellitus, herpes simples, herpes zoster (viremic phase), renal transplantation.
• Any pretreatment with hydrocortisone in the last 4 weeks prior to the first administration of Investigational Medicinal Product.
• Following current medication: cardiac glycosides, saluretics, antidiabetics, cumarin-derivatives, rifampicine, phenytoine, barbiturates, primidone, non-steroidal anti-inflammatory drug (NSAID), salicylate and indometacine, atropine, praziquantel, chloroquine, hydroxychloroquine, mefloquine, somatropine, protireline, cyclosporine, non-depolarising muscle relaxants.
• Pregnancy or lactation period
• Inadequate birth control
• Shift working
• Intercontinental travel within 2 weeks prior to enrollment (to avoid jet-lag)
• History of hypersensitivity to investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
• No subject will be allowed to enrol in this trial more than once.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Schmahl, MD

Role: PRINCIPAL_INVESTIGATOR

Central Institute of Mental Health, Dep. of Psychosomatic and Psychotherapeutic Medicine

Locations

Central Institute of Mental Health, Dep. of Psychosomatic and Psychotherapeutic Medicine

Mannheim, Baden Württemberg6, Germany

Countries

Germany

Other Identifiers

GC-fMRI-PTSD-2010

Identifier Type: OTHER

Identifier Source: secondary_id

GC-fMRI-PTSD

Identifier Type: -

Identifier Source: org_study_id