Posttraumatic Stress DisorderNCT06093906
Positive Processes and Transition to Health (PATH)
A study testing Positive Processes and Transition to Health and Progressive Muscle Relaxation in people with Posttraumatic Stress Disorder and Major Depressive Disorder, run by Case Western Reserve University at 3 sites in United States.
Trial summary
The R33 will be a randomized controlled trial to replicate changes in the targets (unproductive processing, avoidance, reward deficits) from the R61 phase in a larger sample of 135 participants who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Posttraumatic Stress Disorder, Major Depressive Disorder
- What is being tested?
- Positive Processes and Transition to Health and Progressive Muscle Relaxation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 3 sitesUnited States
- Study dates
- 12 Sep 2023to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Destabilizing life event involving profound loss or threat, with a minimum duration of 12 weeks since the event, but occurred within the last 5 years.
- Between the ages of 18 and 65.
- Elevated target: Scores of at least moderate (1 or higher) on at least 2 of the 3 target mechanisms: re- experiencing or ruminative processing of the destabilizing event (PSS-I items: 1, 2, 3, 4 or QIDS-C item 11), avoidance (PSS-I items 6, 7, 8), or reward deficits (PSS-I items 12, 13, or QIDS-C item 13).
Who cannot join
- Current diagnosis of schizophrenia, delusional disorder, or organic mental disorder as defined by DSM-5.
- Current diagnosis of bipolar disorder, depression with psychotic features, or depression severe enough to require immediate psychiatric treatment (i.e., serious suicide risk with intent and plan).
- Severe self-injurious behavior or suicide attempt within the previous three months.
- Unwilling or unable to discontinue current cognitive behavioral psychotherapy.
- No clear memory of the destabilizing event or event occurred before age 3.
- Unstable dose of psychotropic medications in prior 3 months.
- Ongoing intimate relationship with the perpetrator (in assault related event).
- Current diagnosis of a substance use disorder (DSM-5).
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
Norah C Feeny, PhD
Noni Shemenski, BA, 2163680338, noni.shemenski@case.edu
- Recruiting
University of Delaware
Newark, Delaware, 19716
Adele M Hayes, PhD
Matt Paszkiewicz, BA, 3028312215, mattpasz@udel.edu
- Recruiting
University of Washington
Seattle, Washington, 98195
Lori A Zoellner, PhD
Sarah Cornell-Maier, BA, 2066853617, cornelsm@uw.edu
About this study
Official title: Treatment of Stress-Related Psychopathology: Targeting Maladaptive and Adaptive Event Processing
The R33 will be a randomized controlled trial to replicate changes in the targets (unproductive processing, avoidance, reward deficits) from the R61 phase in a larger sample of 135 participants who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related symptoms of PTSD and/or depression, and are elevated on symptoms related to 2 of the 3 therapeutic targets. Additionally, this study will examine Positive Processes and Transition to Health (PATH)'s impact on stressor-related psychopathology in comparison to Progressive Muscle Relaxation (PMR). In the R33 phase, the investigators will examine changes in target mechanisms predicting improvements in PTSD and depressive symptoms, as well as feasibility and acceptability. Patients will receive 6 sessions of PATH or PMR (with 2 boosters, if partial responders). Primary targets will be assessed at pre-treatment, week 3, post-treatment, and at 1- and 3-month follow-up; secondary targets at pre-treatment, weekly during treatment, post-treatment, and at 1- and 3-month follow-ups.
Read the detailed description
Evidence-based psychotherapies for posttraumatic stress disorder (PTSD) and depression consistently produce strong, clinically meaningful effects for many individuals. However, these interventions also have significant dropout rates, a large minority of individuals continue to have debilitating symptoms, and even those who respond may be vulnerable to relapse upon future stressors. More efficient and mechanistically precise interventions are needed. Consistent with the cross-cutting theme of studying the role of the environment in the NIMH Strategic Plan, the etiological role of exposure to destabilizing, stressful life events is common to both PTSD and depression. Not only do they share common distress-related triggers, symptoms, and maintaining processes, but they also commonly co-occur (upwards of 60%). Current PTSD and depression treatments typically focus on their respective disorders rather than on common processes that maintain psychopathology; and, importantly, they do not explicitly target positive adaptive processes associated with resilience. Decades of experimental studies, prospective studies, and psychotherapy trials have identified interconnected maladaptive and adaptive processes associated with persistent psychopathology after stressful, destabilizing events. These maladaptive processes include: 1) unproductive event processing; 2) avoidance; and 3) reward sensitivity and processing deficits. These processes prolong negative mood, interfere with adaptive coping and processing of emotional material, and increase sensitivity to future stressful life events. PATH (Positive Processes and Transition to Health) directly targets these maladaptive processes while also teaching parallel adaptive skills (constructive processing, approach, and positive emotion processing and reward seeking). Six, 90-min sessions target individuals who have experienced a destabilizing life event and have persistent stressor-related symptoms. PATH utilizes life event processing (revisiting, meaning making), focusing repeatedly on an identified destabilizing life event, positive life events, and future events as a framework to identify maladaptive processes and teach constructive processing skills. PATH has the potential to reduce dropout, improve treatment engagement and outcomes, identify potential treatment mechanisms, and ultimately reduce the costly human and economic burden of stressor-related psychopathology.
For the open trial's "Go" to be achieved and to proceed to the R33, two criteria must be met. The first is that at least 2 of the 3 primary targets must change via PATH. A moderate effect size (d = 0.60) was chosen to reflect evidence of clinically meaningful target engagement (see Gold et al., 2017), in line with NIMH guidelines for a preliminary signal of target engagement/efficacy in intervention trials. Second, at least one of the secondary measures must show a moderate effect (d = 0.50) from pre- to post-treatment. The investigators included measures of each of the targets, as they are conceptualized as interrelated parts of a "stuck" system. For "Go" to an R01 after the R33, in addition to target engagement, primary outcomes of PTSD and depression must show clinically meaningful gains (e.g., Barth et al., 2016; Cusak et al., 2016).
In the R33 phase, if the investigators achieve the "Go" criteria, the investigators will conduct a randomized controlled trial comparing PATH to PMR. PMR is a commonly used control condition that is rated as credible and helpful by patients. PMR will consist of six 60-90 minute sessions, focusing on stress management.
- Being tested
- Positive Processes and Transition to Health, Progressive Muscle Relaxation
- Medical subject headings
- Stress Disorders, Post-Traumatic, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positive Processes and Transition to HealthBehavioural
Also called PATH
See arm/group description for details regarding this intervention
Progressive Muscle RelaxationBehavioural
Also called PMR
See arm/group description for details regarding this intervention
| Study group | Role | What they receive |
|---|---|---|
| Positive Processes and Transition to Health (PATH) | Experimental | PATH includes six 60-90 min, weekly sessions, with two booster sessions for partial responders. Session 1 provides the PATH rationale and a review of life events (PATH of life: negative and positive). A rationale for an explicit focus on positive events/emotions will be provided. Sessions 2-4 focus on a verbal narrative of the destabilizing life event, reminiscence and processing of a major positive life event, and real-life practice to enact what was taught. Sessions 5 focuses on constructive processing and provides opportunity for integration and consolidation of learning. Session 6 focuses on future negative and positive events to promote application of new learning and resilience. Booster sessions focus on positive and negative life events since the last session and adaptive processes (constructive processing, approach, and reward). All sessions will include cultivation and elaboration of positive emotions to promote engagement and to build on the benefits of positive emotions. Receives: Behavioral: Positive Processes and Transition to Health |
| Progressive Muscle Relaxation (PMR) | Active comparator | PMR will be adapted from Berstein, Borkoveck, and Hazlett- Stevens (2000). PMR will be conducted in six, 60-90 min individual weekly sessions with a study therapist. Muscle groups are tightened and then relaxed with the attention of the patient focused on the contrast between tension and relaxation. Through regular practice, the person becomes more aware of tension in the body and can induce relaxation as needed (Field, 2009). During the six sessions of training, patients will be encouraged to practice PMR and learn how to deliberately induce physical relaxation to reduce stress and mental tension. Sessions will move from relaxation of 16-muscle groups to 7 muscle groups, 4 muscle groups, and finally to relaxation by recall. Patients will be instructed to practice daily, if possible, but at least two or three times a week, and to integrate the practice into their daily life. They will be provided with audio recordings and homework reporting forms to assist their home PMR exercises. Receives: Behavioral: Progressive Muscle Relaxation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Affective Updating Task
Measure updating of affective information in working memory
Measured: Change from baseline score at 6 weeks (immediately post treatment)
Idiographic Behavioral Approach Task
Use in vivo confrontation with feared or avoided stimuli measuring avoidance behavior
Measured: Change from baseline score at 6 weeks (immediately post treatment)
Probabilistic Reward Task
Assesses reward responsivity
Measured: Change from baseline score at 6 weeks (immediately post treatment)
Secondary outcomes (3)
Posttraumatic Cognitions Inventory
Self-report of negative, overgeneralized stressor-related thoughts
Measured: Change from baseline score at 6 weeks (immediately post treatment)
Behavioral Activation for Depression Scale
Self-report of approach and avoidance in cognitive and behavioral domains (not specific to depression)
Measured: Change from baseline score at 6 weeks (immediately post treatment)
Snaith-Hamilton Pleasure Scale
Self-report measuring the capacity to experience pleasure
Measured: Change from baseline score at 6 weeks (immediately post treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2023
- Study start12 Sep 2023
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress DisorderStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized to receive PATH therapy or PMR.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington, University of Delaware, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Norah Feeny, Case Western Reserve University
- Investigators
- Norah Feeny, PhD, Principal investigator, Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06093906
- Sponsor's protocol ID
- STUDY20191519
- Other IDs
- 4R33MH118401-03
- Status last verified
- Aug 2026
- First submitted
- 17 Oct 2023
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Stress-Related Psychopathology: Targeting Maladaptive and Adaptive Event Processing
- ClinicalTrials.gov ID
- NCT06093906
- Acronym / sponsor ID
- STUDY20191519
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Collaborators
- University of Washington, University of Delaware, National Institute of Mental Health (NIMH)
- Study start
- 12 Sep 2023 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 23 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The R33 will be a randomized controlled trial to replicate changes in the targets (unproductive processing, avoidance, reward deficits) from the R61 phase in a larger sample of 135 participants who have experienced a destabilizing life event involving profound loss or threat, report persistent stressor-related symptoms of PTSD and/or depression, and are elevated on symptoms related to 2 of the 3 therapeutic targets. Additionally, this study will examine Positive Processes and Transition to Health (PATH)'s impact on stressor-related psychopathology in comparison to Progressive Muscle Relaxation (PMR). In the R33 phase, the investigators will examine changes in target mechanisms predicting improvements in PTSD and depressive symptoms, as well as feasibility and acceptability. Patients will receive 6 sessions of PATH or PMR (with 2 boosters, if partial responders). Primary targets will be assessed at pre-treatment, week 3, post-treatment, and at 1- and 3-month follow-up; secondary targets at pre-treatment, weekly during treatment, post-treatment, and at 1- and 3-month follow-ups.
Detailed description
Evidence-based psychotherapies for posttraumatic stress disorder (PTSD) and depression consistently produce strong, clinically meaningful effects for many individuals. However, these interventions also have significant dropout rates, a large minority of individuals continue to have debilitating symptoms, and even those who respond may be vulnerable to relapse upon future stressors. More efficient and mechanistically precise interventions are needed. Consistent with the cross-cutting theme of studying the role of the environment in the NIMH Strategic Plan, the etiological role of exposure to destabilizing, stressful life events is common to both PTSD and depression. Not only do they share common distress-related triggers, symptoms, and maintaining processes, but they also commonly co-occur (upwards of 60%). Current PTSD and depression treatments typically focus on their respective disorders rather than on common processes that maintain psychopathology; and, importantly, they do not explicitly target positive adaptive processes associated with resilience. Decades of experimental studies, prospective studies, and psychotherapy trials have identified interconnected maladaptive and adaptive processes associated with persistent psychopathology after stressful, destabilizing events. These maladaptive processes include: 1) unproductive event processing; 2) avoidance; and 3) reward sensitivity and processing deficits. These processes prolong negative mood, interfere with adaptive coping and processing of emotional material, and increase sensitivity to future stressful life events. PATH (Positive Processes and Transition to Health) directly targets these maladaptive processes while also teaching parallel adaptive skills (constructive processing, approach, and positive emotion processing and reward seeking). Six, 90-min sessions target individuals who have experienced a destabilizing life event and have persistent stressor-related symptoms. PATH utilizes life event processing (revisiting, meaning making), focusing repeatedly on an identified destabilizing life event, positive life events, and future events as a framework to identify maladaptive processes and teach constructive processing skills. PATH has the potential to reduce dropout, improve treatment engagement and outcomes, identify potential treatment mechanisms, and ultimately reduce the costly human and economic burden of stressor-related psychopathology.
For the open trial's "Go" to be achieved and to proceed to the R33, two criteria must be met. The first is that at least 2 of the 3 primary targets must change via PATH. A moderate effect size (d = 0.60) was chosen to reflect evidence of clinically meaningful target engagement (see Gold et al., 2017), in line with NIMH guidelines for a preliminary signal of target engagement/efficacy in intervention trials. Second, at least one of the secondary measures must show a moderate effect (d = 0.50) from pre- to post-treatment. The investigators included measures of each of the targets, as they are conceptualized as interrelated parts of a "stuck" system. For "Go" to an R01 after the R33, in addition to target engagement, primary outcomes of PTSD and depression must show clinically meaningful gains (e.g., Barth et al., 2016; Cusak et al., 2016).
In the R33 phase, if the investigators achieve the "Go" criteria, the investigators will conduct a randomized controlled trial comparing PATH to PMR. PMR is a commonly used control condition that is rated as credible and helpful by patients. PMR will consist of six 60-90 minute sessions, focusing on stress management.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are randomized to receive PATH therapy or PMR.
| Arm | Type | Receives |
|---|---|---|
| Positive Processes and Transition to Health (PATH) | Experimental | Behavioral: Positive Processes and Transition to HealthPATH includes six 60-90 min, weekly sessions, with two booster sessions for partial responders. Session 1 provides the PATH rationale and a review of life events (PATH of life: negative and positive). A rationale for an explicit focus on positive events/emotions will be provided. Sessions 2-4 focus on a verbal narrative of the destabilizing life event, reminiscence and processing of a major positive life event, and real-life practice to enact what was taught. Sessions 5 focuses on constructive processing and provides opportunity for integration and consolidation of learning. Session 6 focuses on future negative and positive events to promote application of new learning and resilience. Booster sessions focus on positive and negative life events since the last session and adaptive processes (constructive processing, approach, and reward). All sessions will include cultivation and elaboration of positive emotions to promote engagement and to build on the benefits of positive emotions. |
| Progressive Muscle Relaxation (PMR) | Active comparator | Behavioral: Progressive Muscle RelaxationPMR will be adapted from Berstein, Borkoveck, and Hazlett- Stevens (2000). PMR will be conducted in six, 60-90 min individual weekly sessions with a study therapist. Muscle groups are tightened and then relaxed with the attention of the patient focused on the contrast between tension and relaxation. Through regular practice, the person becomes more aware of tension in the body and can induce relaxation as needed (Field, 2009). During the six sessions of training, patients will be encouraged to practice PMR and learn how to deliberately induce physical relaxation to reduce stress and mental tension. Sessions will move from relaxation of 16-muscle groups to 7 muscle groups, 4 muscle groups, and finally to relaxation by recall. Patients will be instructed to practice daily, if possible, but at least two or three times a week, and to integrate the practice into their daily life. They will be provided with audio recordings and homework reporting forms to assist their home PMR exercises. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Destabilizing life event involving profound loss or threat, with a minimum duration of 12 weeks since the event, but occurred within the last 5 years.
- Between the ages of 18 and 65.
- Elevated target: Scores of at least moderate (1 or higher) on at least 2 of the 3 target mechanisms: re- experiencing or ruminative processing of the destabilizing event (PSS-I items: 1, 2, 3, 4 or QIDS-C item 11), avoidance (PSS-I items 6, 7, 8), or reward deficits (PSS-I items 12, 13, or QIDS-C item 13).
Key exclusion criteria (8 listed)
- Current diagnosis of schizophrenia, delusional disorder, or organic mental disorder as defined by DSM-5.
- Current diagnosis of bipolar disorder, depression with psychotic features, or depression severe enough to require immediate psychiatric treatment (i.e., serious suicide risk with intent and plan).
- Severe self-injurious behavior or suicide attempt within the previous three months.
- Unwilling or unable to discontinue current cognitive behavioral psychotherapy.
- No clear memory of the destabilizing event or event occurred before age 3.
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 |
|---|---|---|
| Positive Processes and Transition to HealthAlso: PATHSee arm/group description for details regarding this intervention | Behavioural | Positive Processes and Transition to Health (PATH) |
| Progressive Muscle RelaxationAlso: PMRSee arm/group description for details regarding this intervention | Behavioural | Progressive Muscle Relaxation (PMR) |
Primary outcome
Affective Updating Task
Time frame: Change from baseline score at 6 weeks (immediately post treatment)
Measure updating of affective information in working memory
Idiographic Behavioral Approach Task
Time frame: Change from baseline score at 6 weeks (immediately post treatment)
Use in vivo confrontation with feared or avoided stimuli measuring avoidance behavior
Probabilistic Reward Task
Time frame: Change from baseline score at 6 weeks (immediately post treatment)
Assesses reward responsivity
3 secondary outcomes
Posttraumatic Cognitions Inventory
Time frame: Change from baseline score at 6 weeks (immediately post treatment)
Behavioral Activation for Depression Scale
Time frame: Change from baseline score at 6 weeks (immediately post treatment)
Snaith-Hamilton Pleasure Scale
Time frame: Change from baseline score at 6 weeks (immediately post treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- 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.
Norah Feeny, PhD principal investigator
Case Western Reserve University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Positive Processes and Transition to Health and Progressive Muscle Relaxation in people with Posttraumatic Stress Disorder and Major Depressive Disorder, run by Case Western Reserve University at 3 sites 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 3 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Noni Shemenski, BA (216-368-0338, ptsdlab@case.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Affective Updating Task (time frame: Change from baseline score at 6 weeks (immediately post treatment)). The study lists 3 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 19 Aug 2026.