Combined Treatment of Prolonged Exposure and Pramipexole for Posttraumatic Stress Disorder and Depression

• Sponsor: Research Foundation for Mental Hygiene, Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03765138
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 6.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This pilot study aims to test the safety, feasibility, and initial efficacy of combined 10 week treatment of prolonged exposure (PE) and Pramipexole in patients with comorbid posttraumatic stress disorder (PTSD) and depression (MDD). Resting state functional connectivity (rsFC) will be assessed at baseline and en of treatment.

Condition or Disease	Intervention/Treatment	Phase
PTSD; MDD	Combination Product: PE/Pramipexole	Phase 3

Detailed Description

Approximately half of the individuals with posttraumatic stress disorder (PTSD) present with major depressive disorder (MDD). Compared to PTSD alone, patients with comorbid PTSD-MDD demonstrate greater distress and poorer treatment outcome. Functional magnetic resonance imaging (fMRI) show that relative to PTSD alone, PTSD-MDD is associated with decreased resting state functional connectivity (rs-FC) in both fear- and reward-processing circuits. In addition, our data suggest that Prolonged Exposure (PE), first-line PTSD treatment, may successfully target impairments in the fear circuits, but not in the reward circuits, which may explain the treatment-refractory quality of PTSD-MDD.

The goal of this pilot study is to test the feasibility, safety and initial efficacy of an integrated therapeutic approach targeting both fear and reward impairments in PTSD-MDD patients. Specifically, the investigators will examine a combination treatment with PE, shown to effectively address fear circuitry deficits, and Pramipexole, a dopamine agonist, shown to increase reward circuit function and to have promise in treating depression but not previously studied in PTSD. The central hypothesis is that combined PE/Pramipexole will a) improve PTSD and depressive symptoms in PTSD-MDD patients, and b) increase functional connectivity of fear and reward pathways as measured by fMRI rs-FC. In this pilot study, 15 adults aged 18-60 years with PTSD-MDD will receive combined 10-week of PE and Pramipexole up to the maximum dose of 4mg a day. Clinical assessment will be conducted at baseline, week 5, post treatment and at 3-month follow up. Behaviorally assessments including the probabilistic reward task (PRT) and attention allocation tasks, and fMRI scans for resting state functional connectivity (rs-FC) will be conducted at baseline and end of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combined Prolonged Exposure and Pramipexole Treatment for Patients With PTSD and Depression
• Actual Study Start Date: Feb 19, 2019
• Actual Primary Completion Date: Aug 26, 2019
• Actual Study Completion Date: Aug 26, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: PE/Pramipexole Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment.

Combination Product: PE/Pramipexole; Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerable adverse events.

Outcome Measures

Primary Outcome Measures

1. Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) [Baseline, Week 5, Week 10, 3 month follow up]

   The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.

2. Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD). [Baseline, Week 5, Week 10, 3 month follow up]

   The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.

Secondary Outcome Measures

1. Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC). [baseline and week 10.]

   The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males or females between the ages of 18 and 60

2. Current DSM-V diagnosis of PTSD comorbid with MDD

3. CAPS-5 ≥ 25, and 17-item HRSD ≥ 17

4. Able to give consent, fluent in English

Exclusion Criteria:

1. Prior or current diagnosis with traumatic brain injury, bipolar disorder, psychotic disorder, gambling or impulse control disorders, or dementia

2. History of psychosis, psychotic disorder, mania or bipolar disorder

3. Severe substance use disorder excluding nicotine (i.e., nicotine use disorder and mild-moderate alcohol/cannabis use disorder are accepted)

4. Individuals at risk for suicide based on history and current mental state. BDI-II suicide item > 2 or CGI-Severity baseline score of 7.

5. Treatment with antidepressants or other psychotropic medication in the past 4 weeks (or 6 weeks for fluoxetine; an exception will be made for zolpidem used intermittently for sleep).

6. Pregnancy or plans to become pregnant during the period of the study.

7. Current psychotherapy

8. Current unstable or untreated medical illness

9. Any condition that would exclude clinical MRI exam (e.g. pacemaker, paramagnetic metallic prosthesis, surgical clips, shrapnel, necessity for constant medicinal patch, some tattoos, severe obesity, claustrophobia)

10. History of untoward reaction to pramipexole

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• Research Foundation for Mental Hygiene, Inc.

Investigators

• Principal Investigator: Yuval Neria, PhD, Columbia Psyhciatry and New York State Psychiatric Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 12, 2018

More Information

Additional Information:

• PTSD Research and Treatment Program at Columbia Psychaitry

Publications

None provided.

• Responsible Party: Yuval Y Neria, Professor of Medical Psychology, Research Foundation for Mental Hygiene, Inc.
• ClinicalTrials.gov Identifier: NCT03765138
• Other Study ID Numbers: Research Foundation for Mental
• First Posted: Dec 5, 2018
• Last Update Posted: Nov 26, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depression; Pramipexole

Study Results

Participant Flow

Arm/Group Title	PE/Pramipexole
Arm/Group Description	Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment. PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	PE/Pramipexole
Arm/Group Description	Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment. PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 100%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
Description	The CAPS is the gold standard in PTSD assessment. It is a 30-item structured interview used for current (past week or month) and lifetime diagnosis of PTSD. The CAPS was designed to be administered by clinicians and clinical researchers who have a working knowledge of PTSD. The full interview takes 45-60 minutes to administer. Scores range from 0 to 80 with higher values represent a worse outcome.
Time Frame	Baseline, Week 5, Week 10, 3 month follow up

Outcome Measure Data

Analysis Population Description

Participant did not complete protocol.

Arm/Group Title	PE/Pramipexole
Arm/Group Description	Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment. PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.
Measure Participants	0

2. Primary Outcome

Title	Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).
Description	The Hamilton Rating Scale for Depression is a 17-item instrument that was designed to measure frequency and intensity of depressive symptoms in individuals with major depressive disorder. Ratings are made using either a five- or a three-point scale, yielding total scores from 0 to 61, with higher values represent a worse outcome.
Time Frame	Baseline, Week 5, Week 10, 3 month follow up

Outcome Measure Data

Analysis Population Description

Study discontinued

Arm/Group Title	PE/Pramipexole
Arm/Group Description	Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment. PE/Pramipexole: Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission.
Measure Participants	0

3. Secondary Outcome

Title	Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).
Description	The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits
Time Frame	baseline and week 10.

Outcome Measure Data

Analysis Population Description

Study discontinued

Arm/Group Title	PE/Pramipexole
Arm/Group Description	Experimental: Prolonged Exposure/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment. PE/Pramipexole: Experimental: PE/Pramipexole Prolonged Exposure (PE) Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission.
Measure Participants	0

Adverse Events

Time Frame	Up to 5 months
Arm/Group Title	PE/Pramipexole
Arm/Group Description	Experimental: Prolonged Exposure (PE)/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. In addition to receiving PE as described above, patients will have Pramipexole treatment. PE/Pramipexole: Experimental: PE/Pramipexole PE Therapy consists of 10 sessions of 90-minute duration, normally conducted once a week. Elements of PE include imaginal and in vivo exposure to trauma reminders; breathing retraining; cognitive restructuring; and PTSD psychoeducation. Pramipexole: In addition to receiving PE as described above, patients will have Pramipexole treatment. Daily dose will be started at 0.25 mg/day and increased by 0.25 mg/day every 3-4 days to a target of 2.5mg day by week 5. Beginning week 6 daily dose will be increased weekly by 0.5 mg/day to a maximum dose of 4mg. Dose will be increased as tolerated unless the patient has achieved remission and will be decreased in the event of intolerance.
All Cause Mortality
	PE/Pramipexole
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	PE/Pramipexole
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	PE/Pramipexole
	Affected / at Risk (%)	# Events
Total	0/1 (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.