Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01681849
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 91
• Location: 1
• Arms: 3
• Duration (Months): 72
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the effects of the medication paroxetine on symptoms of posttraumatic stress disorder (PTSD) and the brain in women with a history of PTSD related to childhood abuse. The hypothesis is that paroxetine will result in an improvement in PTSD symptoms accompanied by changes in brain functional response to reminders of childhood trauma.

Condition or Disease	Intervention/Treatment	Phase
PTSD	Drug: Placebo; Drug: Paroxetine; Other: Positron Emission Tomography (PET) Imaging	Phase 4

Detailed Description

The main purpose of this study was to look at the effects of paroxetine on PTSD symptoms and brain function in women with posttraumatic stress disorder (PTSD) related to childhood abuse. Participants underwent baseline assessment with of PTSD symptoms measured with the Clinician Administered PTSD Scale (CAPS) and brain function during exposure to traumatic scripts of childhood abuse. Participants then were treated in a randomized double-blind fashion with paroxetine or placebo for three months, followed by a repeat of these assessments.

Specific Aims of this proposal were therefore to:

• Assess the effects of paroxetine on PTSD symptoms

• Assess the effects of paroxetine on brain function in conjunction with exposure to traumatic scripts using positron emission tomography (PET) with O-15 water

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paroxetine Group Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.	Drug: Paroxetine; Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.; Other Names: Paxil ; Other: Positron Emission Tomography (PET) Imaging; Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts
Placebo Comparator: Placebo Group Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.	Drug: Placebo; Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.; Drug: Paroxetine; Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.; Other Names: Paxil ; Other: Positron Emission Tomography (PET) Imaging; Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts
Other: PTSD Negative Women who have experienced early childhood abuse and do not have PTSD will serve as a control group and complete baseline assessments. They do not undergo intervention therefore they are assessed at baseline only.	Other: Positron Emission Tomography (PET) Imaging; Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts

Outcome Measures

Primary Outcome Measures

1. Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score [Baseline, End of Study (Up to 52 Weeks)]

   The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.

Secondary Outcome Measures

1. Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM) [Baseline, 3 Months Post Treatment]

   Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects meet criteria for current PTSD as determined by the Structured Clinical Interview for DSMIV (SCID) interview for PTSD and the Clinician Administered PTSD Scale (CAPS) and have a score of greater than 60 on the CAPS

• history of penetrative sexual abuse which occurred once a month or more, for a period of greater than a year at some time between the ages of 4-13, as assessed by the Early Trauma Inventory (ETI)

• are free of psychotropic medication for four weeks before the study (subjects will not be taken off of medication for the purpose of the study).

• Non-PTSD subjects will be included based on the same criteria with the exception that they do not meet criteria for PTSD.

Exclusion Criteria:

• a history of shrapnel or other foreign bodies which would preclude MRI scanning

• meningitis

• traumatic brain injury

• neurological disorder or organic mental disorder

• history of loss of consciousness

• alcohol abuse or substance abuse or dependence based on the SCID within the past 24 months

• positive pregnancy test as measured by a serum beta-HCG or urine pregnancy test on the morning of the PET scan. Women will be counseled about the risks of pregnancy during the course of the study

• current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia, based on the SCID

• a history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness

• evidence of a major medical or neurological illness on physical examination or as a result of laboratory studies (CBC, BUN, creatinine, blood sugar, electrolytes, liver and thyroid function tests, urinalysis, and EKG)

• positive urine toxicology screen

• history of ongoing violence such as domestic abuse as measured by the ETI-lifetime

• post-menopausal status as measured by menstrual history.

• Non-PTSD subjects will additionally be excluded with current major depression or other major psychiatric disorder based on the SCID.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30306

Sponsors and Collaborators

• Emory University
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: James D. Bremner, MD, Professor

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: J. Douglas Bremner, M.D., Professor of Psychiatry and Radiology, Emory University
• ClinicalTrials.gov Identifier: NCT01681849
• Other Study ID Numbers: IRB00000857; R01MH056120
• First Posted: Sep 10, 2012
• Last Update Posted: Jun 28, 2017
• Last Verified: Jun 1, 2017

• Keywords provided by J. Douglas Bremner, M.D., Professor of Psychiatry and Radiology, Emory University: PTSD; childhood abuse
• Additional relevant MeSH terms: Stress Disorders, Post-Traumatic; Paroxetine

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the Emory Clinic and Emory University Hospitals from September 2006 to November 2013.
Pre-assignment Detail	Of the 91 participants who were consented, 7 were excluded due to not meeting screening criteria.

Arm/Group Title	Paroxetine Group	Placebo Group	PTSD Negative
Arm/Group Description	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months. Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Women who have experienced early childhood abuse and do not have PTSD served as a control group and completed baseline assessments Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.
Period Title: Overall Study
STARTED	15	13	56
COMPLETED	7	6	17
NOT COMPLETED	8	7	39

Baseline Characteristics

Arm/Group Title	Paroxetine Group	Placebo Group	PTSD Negative	Total
Arm/Group Description	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months. Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Women who have experienced early childhood abuse and do not have PTSD served as a control group and completed baseline assessments Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Total of all reporting groups
Overall Participants	15	13	56	84
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	13 100%	56 100%	84 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	15 100%	13 100%	56 100%	84 100%
Male	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%	13 100%	56 100%	84 100%

Outcome Measures

1. Primary Outcome

Title	Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score
Description	The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.
Time Frame	Baseline, End of Study (Up to 52 Weeks)

Outcome Measure Data

Analysis Population Description

Data for participants who completed all study visits were analyzed.

Arm/Group Title	Paroxetine Group	Placebo Group
Arm/Group Description	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months. Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.
Measure Participants	7	6
Baseline	31 (10)	30 (5)
End of Study (Up to 52 Weeks)	20 (10)	25 (6)

2. Secondary Outcome

Title	Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)
Description	Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.
Time Frame	Baseline, 3 Months Post Treatment

Outcome Measure Data

Analysis Population Description

Statistical analyses yielded image data sets in which the values assigned to individual voxels correspond to the t-statistic of the difference in brain blood flow between conditions. Statistical images were displayed with values of z score units.

Arm/Group Title	Paroxetine Group	Placebo Group
Arm/Group Description	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.	Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months. Placebo: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.
Measure Participants	7	6
Number [z-scores]	22	2.68

Adverse Events

Time Frame	Adverse events were collected for the duration of the study and open label period (2 years). Adverse events were collected for all participants who began the study.
Arm/Group Title	Paroxetine Group		Placebo Group		PTSD Negative
Arm/Group Description	Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months. Paroxetine: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.		Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months. Placebo: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Paroxetine: Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months. Positron Emission Tomography (PET) Imaging: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.		Women who have experienced early childhood abuse and do not have PTSD will serve as a control group and complete baseline assessments Positron Emission Tomography (PET) Imaging: Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks.
All Cause Mortality
	Paroxetine Group		Placebo Group		PTSD Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/56 (0%)
Serious Adverse Events
	Paroxetine Group		Placebo Group		PTSD Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Paroxetine Group		Placebo Group		PTSD Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/56 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.