Clinical trial NCT03765138: Combined Treatment of Prolonged Exposure and Pramipexole for Posttraumatic Stress Disorder and Depression
Official title: Combined Prolonged Exposure and Pramipexole Treatment for Patients With PTSD and Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: PTSD
MDD
Lead sponsor: Research Foundation for Mental Hygiene, Inc.
Sponsor class: OTHER
First posted: 2018-12-05
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
timeFrame: Baseline, Week 5, Week 10, 3 month follow up
measure: Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).
timeFrame: Baseline, Week 5, Week 10, 3 month follow up
Secondary outcomes:
measure: Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).
timeFrame: baseline and week 10.
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: Columbia Psyhciatry and New York State Psychiatric Institute
name: Yuval Neria, PhD
role: PRINCIPAL_INVESTIGATOR
References: