PATH vs PMR for PTSD and Depression

Recruiting at2 trial locations

Overseen by Norah Feeny, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Case Western Reserve University

Must not be taking: Psychotropics

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that your dose of psychotropic medications has been stable for the past 3 months.

What data supports the effectiveness of the treatment PATH and PMR for PTSD and Depression?

Research on similar treatments, like Mindfulness-Based Stress Reduction (MBSR) and Multi-modular motion-assisted memory desensitization and reconsolidation (3MDR), shows positive changes in veterans with PTSD, such as improved engagement and emotional processing, which may suggest potential benefits for PATH and PMR. ^{1 2 3 4 5}

How does the PATH vs PMR treatment for PTSD and Depression differ from other treatments?

The PATH vs PMR treatment is unique because it focuses on positive processes and progressive muscle relaxation, which may help improve self-related processes and functional connectivity in the brain, particularly in areas affected by PTSD. This approach is different from traditional therapies that often focus on exposure to trauma memories or medication. ^{6 7 8 9 10}

Research Team

Norah Feeny, PhD

Principal Investigator

Case Western Reserve University

Eligibility Criteria

The PATH trial is for adults aged 18-65 who have experienced a significant life event causing loss or threat within the last 5 years and are dealing with PTSD or depression. Participants should show moderate symptoms in at least two of three areas: re-experiencing, avoidance, or reward deficits. Those with severe mental health conditions like bipolar disorder, psychosis, recent self-harm, substance abuse disorders, or unstable medication use cannot join.

Inclusion Criteria

You have experienced a life-altering event such as loss or threat within the past 5 years, lasting at least 3 months.

I often relive or avoid thoughts of a traumatic event and feel less pleasure in life.

I am between 18 and 65 years old.

Exclusion Criteria

You have engaged in severe self-injury or attempted suicide in the past three months.

I have been diagnosed with schizophrenia, delusional disorder, or an organic mental disorder.

You are currently diagnosed with a substance use disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either PATH or PMR in six 60-90 minute weekly sessions, with two booster sessions for partial responders

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for changes in PTSD and depressive symptoms at 1- and 3-month follow-ups

3 months

2 visits (in-person)

Treatment Details

Interventions

• Positive Processes and Transition to Health (Behavioral Intervention)
• Progressive Muscle Relaxation (Behavioral Intervention)

Trial Overview This study tests the Positive Processes and Transition to Health (PATH) program against Progressive Muscle Relaxation (PMR) in helping individuals cope with stress-related symptoms from PTSD and depression. Each participant will receive six sessions of either PATH or PMR therapy to see which is more effective at improving mental health outcomes.

Participant Groups

Group I: Positive Processes and Transition to Health (PATH) Experimental Treatment 1 Intervention

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.

Group II: Progressive Muscle Relaxation (PMR) Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Case Western Reserve University

Lead Sponsor

Trials

314

Recruited

236,000+

Eric W. Kaler

Case Western Reserve University

Chief Executive Officer since 2021

PhD in Chemical Engineering from the University of Minnesota

Stanton L. Gerson

Case Western Reserve University

Chief Medical Officer since 2020

MD from Harvard Medical School

University of Delaware

Collaborator

Trials

167

Recruited

25,700+

Harry Jiannan Wang

University of Delaware

Chief Executive Officer since 2023

PhD in Business Administration from Pennsylvania State University

Dr. Kenneth Gene Yancey

University of Delaware

Chief Medical Officer

MD from Harvard Medical School

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Dr. Joshua A. Gordon

National Institute of Mental Health (NIMH)

Chief Executive Officer since 2016

MD, PhD

Dr. Shelli Avenevoli

National Institute of Mental Health (NIMH)

Chief Medical Officer

PhD

Findings from Research

The 3MDR intervention effectively engages veterans with treatment-resistant PTSD by facilitating the processing of traumatic memories, leading to positive changes such as increased self-understanding and emotional regulation, even if not all participants experienced symptom improvement.

Veterans reported unique aspects of 3MDR, such as walking towards trauma-related images, which contributed to their treatment experience, suggesting that the intervention may provide benefits beyond just reducing PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceived treatment processes and effects of interactive motion-assisted exposure therapy for veterans with treatment-resistant posttraumatic stress disorder: a mixed methods study. van Gelderen, MJ., Nijdam, MJ., Dubbink, GE., et al.[2021]

In a study of 390 PTSD patients treated with sertraline or paroxetine over 12 weeks, both medications showed better outcomes than placebo, but individual responses varied based on factors like gender and trauma history.

The research identified three distinct response classes among patients: fast responders, those with low pretreatment symptom severity, and those with high pretreatment severity, suggesting that longer time since trauma may enhance treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors and trajectories of treatment response to SSRIs in patients suffering from PTSD. Nøhr, AK., Eriksson, H., Hobart, M., et al.[2022]

In a study of 53 adults with PTSD undergoing cognitive processing therapy (CPT), dropout rates were significantly higher (39.7%) compared to written exposure therapy (6.4%), indicating a need to address factors influencing treatment retention.

The research identified that higher levels of physiological distress and cognitive emotional processing were associated with lower dropout rates, while avoidance behaviors predicted higher dropout, suggesting that targeting these factors early in treatment could improve engagement and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of dropout in cognitive processing therapy for PTSD: An examination of in-session treatment processes. Shayani, DR., Canale, CA., Sloan, DM., et al.[2023]

A study of 2686 veterans with PTSD revealed five distinct treatment response trajectories, indicating that severity of PTSD at intake significantly influences treatment outcomes, with some experiencing minimal change and others showing substantial improvement.

Depression and guilt were identified as key predictors of treatment response, suggesting that addressing these issues before starting PTSD therapy could enhance treatment effectiveness, especially for those with severe PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key patterns and predictors of response to treatment for military veterans with post-traumatic stress disorder: a growth mixture modelling approach. Phelps, AJ., Steel, Z., Metcalf, O., et al.[2018]

In individuals with PTSD, the periaqueductal gray (PAG) shows stronger functional connectivity with the default mode network (DMN) during trauma-related stimulus processing compared to healthy individuals, indicating altered brain function associated with self-related processes.

The study found that the PAG has increased excitatory connectivity to key areas of the DMN (precuneus and medial prefrontal cortex) in PTSD patients, suggesting that these changes may contribute to the clinical symptoms experienced during trauma-related processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hijacked self: Disrupted functional connectivity between the periaqueductal gray and the default mode network in posttraumatic stress disorder using dynamic causal modeling. Terpou, BA., Densmore, M., Théberge, J., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of participation in a mindfulness program for veterans with posttraumatic stress disorder: a randomized controlled pilot study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Perceived treatment processes and effects of interactive motion-assisted exposure therapy for veterans with treatment-resistant posttraumatic stress disorder: a mixed methods study. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

Predictors and trajectories of treatment response to SSRIs in patients suffering from PTSD. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Predictors of dropout in cognitive processing therapy for PTSD: An examination of in-session treatment processes. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Key patterns and predictors of response to treatment for military veterans with post-traumatic stress disorder: a growth mixture modelling approach. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The hijacked self: Disrupted functional connectivity between the periaqueductal gray and the default mode network in posttraumatic stress disorder using dynamic causal modeling. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Psychophysiological assessment of PTSD: a potential research domain criteria construct. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Anatomical and functional connectivity in the default mode network of post-traumatic stress disorder patients after civilian and military-related trauma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Do posttraumatic stress symptoms predict trajectories of sleep disturbance and fatigue in patients with breast cancer? A parallel-process latent growth model. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Mechanisms of Change in Written Exposure Treatment of Posttraumatic Stress Disorder. [2022]