PTSDPhase 3NCT03765138
Combined Treatment of Prolonged Exposure and Pramipexole for Posttraumatic Stress Disorder and Depression
A Phase 3 study testing PE/Pramipexole in people with PTSD and MDD, run by Research Foundation for Mental Hygiene, Inc. at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- What is being tested?
- PE/Pramipexole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2019to 26 Aug 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males or females between the ages of 18 and 60
- Current DSM-V diagnosis of PTSD comorbid with MDD
- CAPS-5 ≥ 25, and 17-item HRSD ≥ 17
- Able to give consent, fluent in English
Who cannot join
- Prior or current diagnosis with traumatic brain injury, bipolar disorder, psychotic disorder, gambling or impulse control disorders, or dementia
- History of psychosis, psychotic disorder, mania or bipolar disorder
- Severe substance use disorder excluding nicotine (i.e., nicotine use disorder and mild-moderate alcohol/cannabis use disorder are accepted)
- Individuals at risk for suicide based on history and current mental state. BDI-II suicide item > 2 or CGI-Severity baseline score of 7.
- 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).
- Pregnancy or plans to become pregnant during the period of the study.
Show all 10Show fewer
- Current psychotherapy
- Current unstable or untreated medical illness
- 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)
- History of untoward reaction to pramipexole
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Combined Prolonged Exposure and Pramipexole Treatment for Patients With PTSD and Depression
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.
Read the 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.
- Being tested
- PE/Pramipexole
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PE/PramipexoleCombination product
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.
| Study group | Role | What they receive |
|---|---|---|
| PE/Pramipexole | Experimental | 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. Receives: Combination Product: PE/Pramipexole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
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.
Measured: Baseline, Week 5, Week 10, 3 month follow up
Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).
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.
Measured: Baseline, Week 5, Week 10, 3 month follow up
Secondary outcomes (1)
Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).
The investigators will use fMRI scans at baseline and posttreatment to assess connectivity in fear and reward circuits
Measured: baseline and week 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2018
- Study start19 Feb 2019
- Primary completion26 Aug 2019
- Study completion26 Aug 2019
Why it stopped: Patient recruitment difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PTSDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research Foundation for Mental Hygiene, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yuval Y Neria, Research Foundation for Mental Hygiene, Inc.
- Investigators
- Yuval Neria, PhD, Principal investigator, Columbia Psyhciatry and New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03765138
- Sponsor's protocol ID
- Research Foundation for Mental
- Status last verified
- Nov 2019
- First submitted
- 2 Dec 2018
- Last updated
- 26 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Prolonged Exposure and Pramipexole Treatment for Patients With PTSD and Depression
- ClinicalTrials.gov ID
- NCT03765138
- Acronym / sponsor ID
- Research Foundation for Mental
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Patient recruitment difficulties
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Research Foundation for Mental Hygiene, Inc.University, hospital or other
- Study start
- 19 Feb 2019 (actual)
- Primary completion
- 26 Aug 2019 (actual)
- Study completion
- 26 Aug 2019 (actual)
- First posted
- 5 Dec 2018 (actual)
- Results
- Posted 26 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PE/Pramipexole | Experimental | Combination Product: PE/PramipexoleExperimental: 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Males or females between the ages of 18 and 60
- Current DSM-V diagnosis of PTSD comorbid with MDD
- CAPS-5 ≥ 25, and 17-item HRSD ≥ 17
- Able to give consent, fluent in English
Key exclusion criteria (10 listed)
- Prior or current diagnosis with traumatic brain injury, bipolar disorder, psychotic disorder, gambling or impulse control disorders, or dementia
- History of psychosis, psychotic disorder, mania or bipolar disorder
- Severe substance use disorder excluding nicotine (i.e., nicotine use disorder and mild-moderate alcohol/cannabis use disorder are accepted)
- Individuals at risk for suicide based on history and current mental state. BDI-II suicide item > 2 or CGI-Severity baseline score of 7.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PE/PramipexoleExperimental: 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. | Combination product | PE/Pramipexole |
Primary outcome
Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: 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.
Change in Depressive Symptoms as Measured by the Hamilton Rating Scale for Depression (HRSD).
Time frame: 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.
1 secondary outcome
Changes in Functional Connectivity of Fear and Reward Pathways as Measured by Functional Magentic Resonance Imaging (fMRI) Resting State Functional Connectivity (Rs-FC).
Time frame: baseline and week 10.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- PTSD Research and Treatment Program at Columbia PsychaitryLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuval Neria, PhD principal investigator
Columbia Psyhciatry and New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PE/Pramipexole in people with PTSD and MDD, run by Research Foundation for Mental Hygiene, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in PTSD Symptoms as Measured by the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) (time frame: Baseline, Week 5, Week 10, 3 month follow up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2019.