Brain Markers of Treatment Response in Post-Traumatic Stress Disorder (PTSD)

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00700999
• Collaborator: (none)
• Enrollment: 65
• Locations: 3
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 21.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to examine if treatment of post-traumatic stress disorder in combat veterans with paroxetine changes brain responses as measured by functional magnetic resonance imaging and if brain responses can predict who will get better with treatment.

Condition or Disease	Intervention/Treatment	Phase
Post-traumatic Stress Disorder	Drug: Paroxetine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Neurofunctional Markers of SSRI Treatment Response in PTSD
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: Arm 1 Intervention-Paroxetine	Drug: Paroxetine; Paroxetine 20-40mg po QD for 12 weeks; Other Names: Paxil (brand name)
No Intervention: Arm 2 No Intervention

Outcome Measures

Primary Outcome Measures

1. Percent Change in Brain Response Measured by Functional Magnetic Resonance Imaging (fMRI) [Baseline and 12 weeks]

   Mean percent change in brain response in the prefrontal cortex during an emotion reappraisal task in the treatment (paroxetine) group and in the Combat Exposed Control group. Target areas are analyzed from fMRI scans which were completed before participants receive treatment and again after participants received 12 weeks of treatment with paroxetine (20-40mg QD). Combat Exposed Control participants received an fMRI scan after signing initial consent and again 12 weeks later.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Veterans with clinical diagnosis of post-traumatic stress disorder from combat related to deployment to Afghanistan/Iraq (Operation Enduring Freedom/Operation Iraqi Freedom)

Exclusion Criteria:

• Intolerance or sensitivity to paroxetine

• Major medical or neurologic illness

• Current psychotropic medication or active psychotherapy treatment

• Other major psychiatric illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jesse Brown VA Medical Center Community-Based Outpatient Clinic Lake Side Divison, Chicago, IL	Chicago	Illinois	United States	60611
2	Jesse Brown VA Medical Center, Chicago, IL	Chicago	Illinois	United States	60612
3	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan	United States	48113

Sponsors and Collaborators

• US Department of Veterans Affairs

Investigators

• Principal Investigator: K. Luan Phan, MD, Jesse Brown VA Medical Center, Chicago, IL

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00700999
• Other Study ID Numbers: MHBA-002-08S
• First Posted: Jun 19, 2008
• Last Update Posted: Jun 3, 2014
• Last Verified: May 1, 2014

• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Paroxetine

Study Results

Participant Flow

Recruitment Details	Participants were recruited in this study from 3/1/09 to 12/31/11. Participants were recruited by flyers in the community and within the Ann Arbor Veterans Affairs Health System and through professional referrals within the Ann Arbor Veterans Affairs Health System through the outpatient psychiatry clinics and primary care clinics.
Pre-assignment Detail	All participants went through an initial screening visit in which they signed the informed consent document and completed multiple assessments and a medical evaluation in order to assure that they were able to participate in the study and that they did not meet any exclusionary conditions.

Arm/Group Title	Treatment (Paroxetine) Group	Combat Exposed Controls
Arm/Group Description	Veterans returning from OEF/OIF with documented exposure to combat trauma who meet criteria for DSM-IV diagnosis of PTSD. Completed 12 weeks of treatment with paroxetine (20-40mg QD)	Veterans returning from OEF/OIF with documented exposure to combat trauma who do not meet criteria for DSM-IV diagnosis of PTSD
Period Title: Overall Study
STARTED	36	29
First MRI Scan	29	22
Second MRI Scan	19	18
COMPLETED	21	20
NOT COMPLETED	15	9

Baseline Characteristics

Arm/Group Title	Treatment Group	Combat Exposed Controls	Total
Arm/Group Description	Veterans returning from OEF/OIF with documented exposure to combat trauma who meet criteria for DSM-IV diagnosis of PTSD	veterans returning from OEF/OIF with documented exposure to combat trauma who do not meet criteria for DSM-IV diagnosis of PTSD	Total of all reporting groups
Overall Participants	29	22	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 100%	22 100%	51 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	1 4.5%	1 2%
Male	29 100%	21 95.5%	50 98%
Region of Enrollment (participants) [Number]
United States	29 100%	22 100%	51 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Brain Response Measured by Functional Magnetic Resonance Imaging (fMRI)
Description	Mean percent change in brain response in the prefrontal cortex during an emotion reappraisal task in the treatment (paroxetine) group and in the Combat Exposed Control group. Target areas are analyzed from fMRI scans which were completed before participants receive treatment and again after participants received 12 weeks of treatment with paroxetine (20-40mg QD). Combat Exposed Control participants received an fMRI scan after signing initial consent and again 12 weeks later.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

The number of participants analyzed is only 17 in each arm. The total number of participants in the Intervention group who completed fMRI scans pre-treatment and post treatment is only 19, in the Combat Exposed Control Group it is 18. Three of the participants scans were removed from data analysis due to the level of movement during the scan.

Arm/Group Title	Treatment (Paroxetine) Group	Combat Exposed Control
Arm/Group Description	Veterans returning from OEF/OIF with documented exposure to combat trauma who meet criteria for DSM-IV diagnosis of PTSD	Veterans returning from OEF/OIF with documented exposure to combat trauma who do not meet criteria for DSM-IV diagnosis of PTSD.
Measure Participants	17	17
Mean (Standard Deviation) [percent change in BOLD signal]	-.92 (0.90)	.07 (1.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Paroxetine) Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) 95%; -1.38 to -0.45
	Parameter Dispersion	Type: Standard Deviation; Value: 0.90
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Combat Exposed Control
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.869
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.07
	Confidence Interval	(2-Sided) 95%; -.84 to .99
	Parameter Dispersion	Type: Standard Deviation; Value: 1.78
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	In the adverse events described below the total number of participants at risk for other adverse events is not consistent with the total number of participants at risk for other adverse events in the Arms/Groups i.e., "36" and "29" respectively. The numbers are correct due to only 22 participants having participated in the fMRI scans.
Arm/Group Title	Treatment (Paroxetine) Group		Combat Exposed Controls
Arm/Group Description	Veterans returning from OEF/OIF with documented exposure to combat trauma who meet criteria for DSM-IV diagnosis of PTSD		Veterans returning from OEF/OIF with documented exposure to combat trauma who do not meet criteria for DSM-IV diagnosis of PTSD
All Cause Mortality
	Treatment (Paroxetine) Group		Combat Exposed Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment (Paroxetine) Group		Combat Exposed Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Paroxetine) Group		Combat Exposed Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/36 (77.8%)		1/29 (3.4%)
Psychiatric disorders
Psychological/Emotional Adverse Event	5/28 (17.9%)	5	0/29 (0%)	0
Anxiety experience during fMRI scanning	2/29 (6.9%)	2	1/22 (4.5%)	1
Physical Side Effect to Medication - Blurred Vision	8/36 (22.2%)	8	0/0 (NaN)	0
Physical Side Effect to Medication - Chest Pain	7/36 (19.4%)	7	0/0 (NaN)	0
Physical Side Effect to Medication - Constipation	8/36 (22.2%)	8	0/0 (NaN)	0
Physical Side Effect to Medication - Diarrhea	9/36 (25%)	9	0/0 (NaN)	0
Physical Side Effect to Medication - Difficulty Urinating	2/36 (5.6%)	2	0/0 (NaN)	0
Physical Side Effect to Medication - Difficulty with erections or sexual functioning	17/36 (47.2%)	17	0/0 (NaN)	0
Physical Side Effect to Medication - Dizziness	13/36 (36.1%)	13	0/0 (NaN)	0
Physical Side Effect to Medication - Drowsiness	24/36 (66.7%)	24	0/0 (NaN)	0
Physical Side Effect to Medication - Dry mouth	14/36 (38.9%)	14	0/0 (NaN)	0
Physical Side Effect to Medication - Feeling that familiar things are strange or unreal	9/36 (25%)	9	0/0 (NaN)	0
Physical Side Effect to Medication - Headaches	24/36 (66.7%)	24	0/0 (NaN)	0
Physical Side Effect to Medication - Heart pounding or racing	20/36 (55.6%)	20	0/0 (NaN)	0
Physical Side Effect to Medication - Hot or cold spells	11/36 (30.6%)	11	0/0 (NaN)	0
Physical Side Effect to Medication - Increased salivation	2/36 (5.6%)	2	0/0 (NaN)	0
Physical Side Effect to Medication - Nausea	17/36 (47.2%)	17	0/0 (NaN)	0
Physical Side Effect to Medication - Nervousness	18/36 (50%)	18	0/0 (NaN)	0
Physical Side Effect to Medication - Numbness or tingling	15/36 (41.7%)	15	0/0 (NaN)	0
Physical Side Effect to Medication - Overeating	12/36 (33.3%)	12	0/0 (NaN)	0
Physical Side Effect to Medication - Panic	13/36 (36.1%)	13	0/0 (NaN)	0
Physical Side Effect to Medication - Poor Appetite	17/36 (47.2%)	17	0/0 (NaN)	0
Physical Side Effect to Medication - Soreness	23/36 (63.9%)	23	0/0 (NaN)	0
Physical Side Effect to Medication - Sweating	15/36 (41.7%)	15	0/0 (NaN)	0
Physical Side Effect to Medication - Tense	25/36 (69.4%)	25	0/0 (NaN)	0
Physical Side Effect to Medication - Trembling	12/36 (33.3%)	12	0/0 (NaN)	0
Physical Side Effect to Medication - Trouble falling asleep	25/36 (69.4%)	25	0/0 (NaN)	0
Physical Side Effect to Medication - Trouble getting your breath	8/36 (22.2%)	8	0/0 (NaN)	0
Physical Side Effect to Medication - Trouble remembering things	26/36 (72.2%)	26	0/0 (NaN)	0
Physical Side Effect to Medication - Trouble staying asleep	24/36 (66.7%)	24	0/0 (NaN)	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.