Posttraumatic Stress DisorderPhase 4PROGrESSNCT01524133
PROlonGed ExpoSure Sertraline
A Phase 4 study testing Sertraline and Prolonged Exposure Therapy in people with Posttraumatic Stress Disorder, run by VA Ann Arbor Healthcare System at 4 sites in United States.
Trial summary
The current research study aims to compare the effectiveness of two proven treatments for posttraumatic stress disorder (PTSD): Prolonged Exposure (PE), sertraline, and their combination. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- Sertraline and Prolonged Exposure Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 223 participants
- Where
- 4 sitesUnited States
- Study dates
- Nov 2011to May 2017
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient is an Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combat veteran with chronic posttraumatic stress disorder (PTSD) or significant PTSD symptoms (Clinician Administered Posttraumatic Stress Disorder Scale [CAPS] >= 50) of at least 3 months duration
Who cannot join
- Current, imminent risk of suicide (as indicated on C-SSRS)
- Active psychosis
- Alcohol or substance dependence in the past 8 weeks
- Unable to attend regular appointments
- Prior intolerance or failure of adequate trial of prolonged exposure (PE) or sertraline (SERT) (defined as at least 2 months of SERT at least 100mg/day)
- Medical illness likely to result in hospitalization or for which treatments are contraindicated (based on lab results, medical history and physical exam)
Show all 9Show fewer
- Serious cognitive impairment (as evidenced by cognitive impairment felt likely to interfere with the ability to participate meaningfully in the study)
- Concurrent antidepressants or antipsychotics
- Pregnant females
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Veterans Affairs Ann Arbor Healthcare System
Ann Arbor, Michigan, 48105
Massachusetts General Hospital
Boston, Massachusetts, 02114
VA San Diego Healthcare System
San Diego, California, 92161
Ralph H. Johnson VA Medical Center/Savannah Primary Care Clinic
Savannah, Georgia, 31406
About this study
Official title: Randomized Trial of Sertraline, Prolonged Exposure, and Their Combination for Post-traumatic Stress Disorder (PTSD) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF).
The current research study aims to compare the effectiveness of two proven treatments for posttraumatic stress disorder (PTSD): Prolonged Exposure (PE), sertraline, and their combination. In addition, the investigators are examining predictors of response to these two treatments and how PTSD symptoms, thoughts, and biological factors may be changed by such treatments. Biological mechanisms of change are also examined including emotion processing and regulation in fMRI, HPA axis function, and genetics and genomics. In addition, the investigators will examine acceptability of each treatment and reasons for ending treatment.
- Conditions
- Posttraumatic Stress Disorder
- Being tested
- Sertraline, Prolonged Exposure Therapy
- Keywords
- combat-related PTSD, Posttraumatic stress disorder, prolonged exposure therapy, sertraline, military, veterans, VA hospital, mental illness
- Medical subject headings
- Stress Disorders, Post-Traumatic, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
Also called Zoloft
Initial baseline dose of 25 mg/day. Clinician will attempt to titrate patients to at least 100 mg/day and up to 200 mg/day if tolerated by week 8.
Prolonged Exposure TherapyBehavioural
up to 13 sessions of prolonged exposure
| Study group | Role | What they receive |
|---|---|---|
| Sertraline + enhanced medication management (SERT/EMM) | Active comparator | 24 weeks of sertraline + enhanced medication management Receives: Drug: Sertraline |
| Prolonged Exposure + sertraline (PE/SERT) | Active comparator | Up to 13 sessions of prolonged exposure therapy + 24 weeks of sertraline Receives: Drug: Sertraline; Behavioral: Prolonged Exposure Therapy |
| Prolonged Exposure + placebo (PE/PLB) | Active comparator | Up to 13 sessions of prolonged exposure therapy + 24 weeks of placebo Receives: Behavioral: Prolonged Exposure Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
Total Score; Range 0-136 with increasing PTSD severity as scores increase
Measured: 24 weeks
Secondary outcomes (1)
Patient Health Questionnaire-15
PHQ-15; measures somatization and ranges from 0 to 30 and 0-9 is considered minimal/low, 10-14 is moderate, and 15-30 is severe
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startNov 2011
- Primary completionDec 2016
- Study completionMay 2017
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.
- Publications (10)Papers the sponsor has linked to this study.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 223 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Ann Arbor Healthcare System
- Sponsor type
- US federal agency
- Collaborators
- U.S. Army Medical Research and Development Command
- Responsible party
- Principal investigator, Sheila Rauch, Atlanta VA Medical Center
- Investigators
- Sheila Rauch, PhD, Principal investigator, VA Ann Arbor Healthcare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01524133
- Sponsor's protocol ID
- PROGrESS
- Acronym
- PROGrESS
- Status last verified
- Jan 2018
- First submitted
- 27 Jan 2012
- Last updated
- 28 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rauch SAM, Kim HM, Hellman N, Acierno R, Simon NM, King AP, B Allard C. PTSD treatment impacts on pain: secondary analysis of sertraline, prolonged exposure, and their combination. Eur J Psychotraumatol. 2026 Dec;17(1):2727209. doi: 10.1080/20008066.2026.2727209. Epub 2026 Sep 21.
PubMed 42766718Allard CB, Norman SB, Straus E, Kim HM, Stein MB, Simon NM, Rauch SAM; PROGrESS Study Team. Reductions in guilt cognitions following prolonged exposure and/or sertraline predict subsequent improvements in PTSD and depression. J Behav Ther Exp Psychiatry. 2021 Dec;73:101666. doi: 10.1016/j.jbtep.2021.101666. Epub 2021 Jun 1.
PubMed 34147766Rauch SAM, Kim HM, Lederman S, Sullivan G, Acierno R, Tuerk PW, Simon NM, Venners MR, Norman SB, Allard CB, Porter KE, Martis B, Bui E, Baker AW; PROGrESS Team. Predictors of Response to Prolonged Exposure, Sertraline, and Their Combination for the Treatment of Military PTSD. J Clin Psychiatry. 2021 Jun 15;82(4):20m13752. doi: 10.4088/JCP.20m13752.
PubMed 34133087Sheynin J, Duval ER, King AP, Angstadt M, Phan KL, Simon NM, Rauch SAM, Liberzon I. Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder. Depress Anxiety. 2020 Oct;37(10):1037-1046. doi: 10.1002/da.23075. Epub 2020 Jul 15.
PubMed 32668087Rauch SAM, King A, Kim HM, Powell C, Rajaram N, Venners M, Simon NM, Hamner M, Liberzon I. Cortisol awakening response in PTSD treatment: Predictor or mechanism of change. Psychoneuroendocrinology. 2020 Aug;118:104714. doi: 10.1016/j.psyneuen.2020.104714. Epub 2020 May 15.
PubMed 32446108Duval ER, Sheynin J, King AP, Phan KL, Simon NM, Martis B, Porter KE, Norman SB, Liberzon I, Rauch SAM. Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder. Depress Anxiety. 2020 Jul;37(7):670-681. doi: 10.1002/da.23022. Epub 2020 Apr 19.
PubMed 32306485Joshi SA, Duval ER, Sheynin J, King AP, Phan KL, Martis B, Porter KE, Liberzon I, Rauch SAM. Neural correlates of emotional reactivity and regulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder. Psychiatry Res Neuroimaging. 2020 May 30;299:111062. doi: 10.1016/j.pscychresns.2020.111062. Epub 2020 Mar 5.
PubMed 32278278Goetter EM, Hoeppner SS, Khan AJ, Charney ME, Wieman S, Venners MR, Avallone KM, Rauch SAM, Simon NM. Combat-Related Posttraumatic Stress Disorder and Comorbid Major Depression in U.S. Veterans: The Role of Deployment Cycle Adversity and Social Support. J Trauma Stress. 2020 Jun;33(3):276-284. doi: 10.1002/jts.22496. Epub 2020 Mar 26.
PubMed 32216142Rauch SAM, Kim HM, Powell C, Tuerk PW, Simon NM, Acierno R, Allard CB, Norman SB, Venners MR, Rothbaum BO, Stein MB, Porter K, Martis B, King AP, Liberzon I, Phan KL, Hoge CW. Efficacy of Prolonged Exposure Therapy, Sertraline Hydrochloride, and Their Combination Among Combat Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Feb 1;76(2):117-126. doi: 10.1001/jamapsychiatry.2018.3412.
PubMed 30516797Rauch SAM, Simon NM, Kim HM, Acierno R, King AP, Norman SB, Venners MR, Porter K, Phan KL, Tuerk PW, Allard C, Liberzon I, Rothbaum BO, Martis B, Stein MB, Hoge CW. Integrating biological treatment mechanisms into randomized clinical trials: Design of PROGrESS (PROlonGed ExpoSure and Sertraline Trial). Contemp Clin Trials. 2018 Jan;64:128-138. doi: 10.1016/j.cct.2017.10.013. Epub 2017 Oct 29.
PubMed 29081351
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Sertraline, Prolonged Exposure, and Their Combination for Post-traumatic Stress Disorder (PTSD) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF).
- ClinicalTrials.gov ID
- NCT01524133
- Acronym / sponsor ID
- PROGrESS / PROGrESS
- Conditions
- Posttraumatic Stress Disorder
- Keywords
- combat-related PTSD, Posttraumatic stress disorder, prolonged exposure therapy, sertraline, military, veterans, VA hospital, mental illness
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 223 participants (actual)
- Lead sponsor
- VA Ann Arbor Healthcare SystemUS federal agency
- Collaborators
- U.S. Army Medical Research and Development Command
- Study start
- Nov 2011
- Primary completion
- Dec 2016 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Posted 28 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current research study aims to compare the effectiveness of two proven treatments for posttraumatic stress disorder (PTSD): Prolonged Exposure (PE), sertraline, and their combination. In addition, the investigators are examining predictors of response to these two treatments and how PTSD symptoms, thoughts, and biological factors may be changed by such treatments. Biological mechanisms of change are also examined including emotion processing and regulation in fMRI, HPA axis function, and genetics and genomics. In addition, the investigators will examine acceptability of each treatment and reasons for ending treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sertraline + enhanced medication management (SERT/EMM) | Active comparator | Drug: Sertraline24 weeks of sertraline + enhanced medication management |
| Prolonged Exposure + sertraline (PE/SERT) | Active comparator | Drug: Sertraline, Behavioral: Prolonged Exposure TherapyUp to 13 sessions of prolonged exposure therapy + 24 weeks of sertraline |
| Prolonged Exposure + placebo (PE/PLB) | Active comparator | Behavioral: Prolonged Exposure TherapyUp to 13 sessions of prolonged exposure therapy + 24 weeks of placebo |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Patient is an Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combat veteran with chronic posttraumatic stress disorder (PTSD) or significant PTSD symptoms (Clinician Administered Posttraumatic Stress Disorder Scale [CAPS] >= 50) of at least 3 months duration
Key exclusion criteria (9 listed)
- Current, imminent risk of suicide (as indicated on C-SSRS)
- Active psychosis
- Alcohol or substance dependence in the past 8 weeks
- Unable to attend regular appointments
- Prior intolerance or failure of adequate trial of prolonged exposure (PE) or sertraline (SERT) (defined as at least 2 months of SERT at least 100mg/day)
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 |
|---|---|---|
| SertralineAlso: ZoloftInitial baseline dose of 25 mg/day. Clinician will attempt to titrate patients to at least 100 mg/day and up to 200 mg/day if tolerated by week 8. | Drug | Prolonged Exposure + sertraline (PE/SERT), Sertraline + enhanced medication management (SERT/EMM) |
| Prolonged Exposure Therapyup to 13 sessions of prolonged exposure | Behavioural | Prolonged Exposure + placebo (PE/PLB), Prolonged Exposure + sertraline (PE/SERT) |
Primary outcome
Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
Time frame: 24 weeks
Total Score; Range 0-136 with increasing PTSD severity as scores increase
1 secondary outcome
Patient Health Questionnaire-15
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42766718Rauch SAM, Kim HM, Hellman N, Acierno R, Simon NM, King AP, B Allard C. PTSD treatment impacts on pain: secondary analysis of sertraline, prolonged exposure, and their combination. Eur J Psychotraumatol. 2026 Dec;17(1):2727209. doi: 10.1080/20008066.2026.2727209. Epub 2026 Sep 21.
- Derived from this study: PubMed 34147766Allard CB, Norman SB, Straus E, Kim HM, Stein MB, Simon NM, Rauch SAM; PROGrESS Study Team. Reductions in guilt cognitions following prolonged exposure and/or sertraline predict subsequent improvements in PTSD and depression. J Behav Ther Exp Psychiatry. 2021 Dec;73:101666. doi: 10.1016/j.jbtep.2021.101666. Epub 2021 Jun 1.
- Derived from this study: PubMed 34133087Rauch SAM, Kim HM, Lederman S, Sullivan G, Acierno R, Tuerk PW, Simon NM, Venners MR, Norman SB, Allard CB, Porter KE, Martis B, Bui E, Baker AW; PROGrESS Team. Predictors of Response to Prolonged Exposure, Sertraline, and Their Combination for the Treatment of Military PTSD. J Clin Psychiatry. 2021 Jun 15;82(4):20m13752. doi: 10.4088/JCP.20m13752.
- Derived from this study: PubMed 32668087Sheynin J, Duval ER, King AP, Angstadt M, Phan KL, Simon NM, Rauch SAM, Liberzon I. Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder. Depress Anxiety. 2020 Oct;37(10):1037-1046. doi: 10.1002/da.23075. Epub 2020 Jul 15.
- Derived from this study: PubMed 32446108Rauch SAM, King A, Kim HM, Powell C, Rajaram N, Venners M, Simon NM, Hamner M, Liberzon I. Cortisol awakening response in PTSD treatment: Predictor or mechanism of change. Psychoneuroendocrinology. 2020 Aug;118:104714. doi: 10.1016/j.psyneuen.2020.104714. Epub 2020 May 15.
- Derived from this study: PubMed 32306485Duval ER, Sheynin J, King AP, Phan KL, Simon NM, Martis B, Porter KE, Norman SB, Liberzon I, Rauch SAM. Neural function during emotion processing and modulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder. Depress Anxiety. 2020 Jul;37(7):670-681. doi: 10.1002/da.23022. Epub 2020 Apr 19.
- Derived from this study: PubMed 32278278Joshi SA, Duval ER, Sheynin J, King AP, Phan KL, Martis B, Porter KE, Liberzon I, Rauch SAM. Neural correlates of emotional reactivity and regulation associated with treatment response in a randomized clinical trial for posttraumatic stress disorder. Psychiatry Res Neuroimaging. 2020 May 30;299:111062. doi: 10.1016/j.pscychresns.2020.111062. Epub 2020 Mar 5.
- Derived from this study: PubMed 32216142Goetter EM, Hoeppner SS, Khan AJ, Charney ME, Wieman S, Venners MR, Avallone KM, Rauch SAM, Simon NM. Combat-Related Posttraumatic Stress Disorder and Comorbid Major Depression in U.S. Veterans: The Role of Deployment Cycle Adversity and Social Support. J Trauma Stress. 2020 Jun;33(3):276-284. doi: 10.1002/jts.22496. Epub 2020 Mar 26.
- Derived from this study: PubMed 30516797Rauch SAM, Kim HM, Powell C, Tuerk PW, Simon NM, Acierno R, Allard CB, Norman SB, Venners MR, Rothbaum BO, Stein MB, Porter K, Martis B, King AP, Liberzon I, Phan KL, Hoge CW. Efficacy of Prolonged Exposure Therapy, Sertraline Hydrochloride, and Their Combination Among Combat Veterans With Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Feb 1;76(2):117-126. doi: 10.1001/jamapsychiatry.2018.3412.
- Derived from this study: PubMed 29081351Rauch SAM, Simon NM, Kim HM, Acierno R, King AP, Norman SB, Venners MR, Porter K, Phan KL, Tuerk PW, Allard C, Liberzon I, Rothbaum BO, Martis B, Stein MB, Hoge CW. Integrating biological treatment mechanisms into randomized clinical trials: Design of PROGrESS (PROlonGed ExpoSure and Sertraline Trial). Contemp Clin Trials. 2018 Jan;64:128-138. doi: 10.1016/j.cct.2017.10.013. Epub 2017 Oct 29.
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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.
Sheila Rauch, PhD principal investigator
VA Ann Arbor Healthcare System
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sertraline and Prolonged Exposure Therapy in people with Posttraumatic Stress Disorder, run by VA Ann Arbor Healthcare System at 4 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 1 inclusion and 9 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: finished, as of the sponsor's last update on 28 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 28 Feb 2018). 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?
Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01524133, which also lists 10 linked publications.
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 28 Feb 2018.