Predicting SSRI Efficacy in Veterans With PTSD

NCT04183205 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: MHBB-028-17F
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

This is a research study to examine the effectiveness of a brief screening method that may predict which people with posttraumatic stress disorder (PTSD) or depression are most likely to show a positive response to selective serotonin reuptake inhibitor (SSRI) medications. Participants will be recruited over approximately 5.25 years, until at least 94 participants complete the 17 week study.

Conditions

Posttraumatic Stress Disorder; Major Depressive Disorder

Keywords

Treatment; Posttraumatic Stress Disorder (PTSD); selective serotonin re-uptake inhibitor (SSRI); loudness dependence of auditory evoked potentials; Electrophysiology; Depression

Outcome Measures

Primary Outcomes (1)

• Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Change

  The CAPS-5 is the "gold standard" clinical interview for assessing PTSD. This measure will be used to characterize the sample regarding PTSD diagnosis and as a measure of PTSD severity. Each of the 20 symptoms of PTSD included in DSM-5 is rated on a 5-point scale ranging from 0-4, with a 0 or 1 indicating that the symptom is absent or subthreshold and a score of 2-4 indicating that a symptom has reached the threshold to be included as a symptom and ranges in severity from moderate to extreme. The total range of the CAPS-5 is 0-80.

  Administered at screening session 1, and weeks 0, 2, 6, and 14

Secondary Outcomes (6)

• Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) Change

  Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14

• Hamilton Depression Rating Scale (HAM-D) Change

  Administered at weeks 0, 2, 6 and 14

• Depression Anxiety Stress Scales (DASS-21) Change

  Administered at screening session 1, and weeks 0, 2, 6, and 14

• PTSD Checklist for DSM-5 (PCL-5) Change

  Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14

• The Positive and Negative Affect Schedule (PANAS) Change

  Administered at screening session 1, and weeks 0, 2, 6, and 14

Study Arms (2)

Placebo only arm

PLACEBO COMPARATOR

For individuals who are placebo responders during the 2 week placebo lead in phase, they will remain on placebo for the duration of the study (i.e., the 12 weeks where the placebo non-responders are taking sertraline).

Diagnostic Test: LDAEP; Drug: Placebo

Sertraline arm

ACTIVE COMPARATOR

After the 2-week placebo lead-in phase, placebo-non responders will receive sertraline 25 mg daily for 2 weeks. Thereafter, sertraline will be increased flexibly by 25 to 50 mg per day (at a rate no higher than 50 mg per week) to achieve a total daily dose of 50 to 200 mg, based on clinical response and tolerability, with a maximum dose of 200 mg/d. Subjects unable to tolerate higher doses may be dropped back to the previous dose and remain at that dose for the remainder of the study.

Diagnostic Test: LDAEP; Drug: Placebo; Drug: sertraline

Interventions

LDAEP DIAGNOSTIC_TEST

This is an ERP task in which participants hear a series of tones ranging from 74dB to 104dB and electrophysiological activity is measured throughout. For each participant average P2 scores are derived for the 74dB tones, 84dB tones, 94dB tones, and 104dB tones. Then, LDAEP is defined as the slope of these average P2 scores.

Placebo only arm; Sertraline arm

Placebo DRUG

placebo pills of the same size, color and taste as the active drug will be administered

Placebo only arm; Sertraline arm

sertraline DRUG

Sertraline is an FDA approved SSRI for treatment of PTSD.

Also known as: zoloft

Sertraline arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• has a history of trauma exposure as defined by criterion A of PTSD in the DSM-5
• meets diagnostic criteria for PTSD, subthreshold PTSD, or MDD as defined by DSM-5
• study psychiatrist's judgment that SSRIs are an acceptable treatment option for the participant's presenting concerns, and
• interest in starting a trial of an SSRI

You may not qualify if:

• current or past history of bipolar I disorder, schizophrenic or other psychotic disorders
• current organic brain disorder including severe traumatic brain injury, factitious disorder, or malingering
• pregnancy
• major neurological problems
• current moderate or severe substance use disorder
• active risk to self or others
• evidence of clinically significant hepatic or renal disease or any other acute or unstable medical condition that might interfere with safe conduct of the study
• intolerance or hypersensitivity to sertraline
• failed past trial of sertraline (confirmed by medical record review)
• use of drugs that directly affect the serotonin system (e.g., SNRIs, antipsychotics) within 3 months of the study
• use of an SSRI within 3 months of the study. Use of other psychotropic medications must have been stable for 3 months prior to enrollment and remain stable throughout participation
• hearing impairment for 780 Hz tones
• current enrollment in trauma-focused psychotherapy
• for those participants who currently have a non-VA or VA psychiatrist or primary care provider who is willing to prescribe medications, they must be willing to sign a release of information (ROI) for study staff to communicate with their providers and the provider believes that including the participant in the study is potentially appropriate.
• As discussed above, the investigators will inform the participant that the investigators will share the following information with their current relevant care provider:

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Middlebury College: collaborator
• Massachusetts General Hospital: collaborator
• Ralph H. Johnson VA Medical Center: collaborator

Study Sites (2)

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817, United States

Location

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5703, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Depressive Disorder, Major; Depression

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Suzanne Pineles, PhD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants will be unaware of whether or not they are on placebo or sertraline at any given moment and the placebo and sertraline capsules look identical. The outcomes assessor is unaware of the study design, study hypotheses, and whether a participant is on placebo or sertraline.
• Purpose: SCREENING
• Intervention Model: SEQUENTIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: All eligible participants will first undergo a 2 week placebo lead in. Following this 2 week period, placebo responders will remain on placebo. All other participants will begin a 12 week sertraline trial.

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: December 3, 2019
• Study Start: September 11, 2019
• Primary Completion: March 30, 2025
• Study Completion: March 31, 2025
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be available within a year of submission of the final report.

Locations

US (2)