Clinical trial NCT04183205: Predicting SSRI Efficacy in Veterans With PTSD
Official title: An Electrophysiological Predictor of SSRI Response in Veterans With PTSD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
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
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Middlebury College
name: Massachusetts General Hospital
name: Ralph H. Johnson VA Medical Center
First posted: 2019-12-03
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: SCREENING

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.

Detailed description: Selective serotonin reuptake inhibitors (SSRIs) are prescribed to approximately 60% of Veterans with PTSD treated within the Veterans Health Administration (VHA). However, many patients are not responsive to SSRIs. Currently, there is no way to determine whether a particular patient will benefit from an SSRI; treatment is primarily accomplished through 'trial and error' over several weeks or months. The overarching goal of this study is to investigate the pre-treatment usefulness of a simple electrophysiological test for predicting the likelihood of a favorable response to an SSRI. This study will investigate whether a brief pre-treatment auditory event-related potentials procedure \[referred to going forward as "Loudness Dependence of Auditory Evoked Potentials" (LDAEP)\] offers a means for predicting treatment response to an SSRI for men and women diagnosed with PTSD or depression.

This study has four aims: 1) To determine the strength of the relationship between LDAEP and clinical response to SSRI treatment. 2) To determine LDAEP cut-off values that would enable clinicians to make individualized SSRI treatment recommendations. 3) To assess the usefulness of change in LDAEP as an objective measure of SSRI response. 4) Exploratory: To determine whether the relationship between LDAEP and clinical response to sertraline differs between men and women.

Means to Protect Subjects' Identities:

To ensure confidentiality, questionnaire and interview data will be stored in locked filing cabinets within locked offices. Each participant will have his or her own participant number and these numbers will be the only means by which participant information can be identified. Electronic data will be stored on a secure private, password-protected drive that can only be accessed by members of the study team and labeled only with the participant number. One list of names and participant numbers will be kept on a private, password-protected computer account on a separate drive from the de-identified data and accessible only to the study team.

ADMINISTRATION OF DRUGS IN RESEARCH NOT FUNDED BY NIH Description Of Identification Of Drug: SERTRALINE. Because the goal of this study is to identify pre-treatment predictors of SSRI response that ultimately could be used in routine clinical care, the investigators designed the study with ecological validity in mind. Specifically, the investigators chose sertraline as the study medication because it is: a) the most commonly prescribed SSRI in the US, b) one of only two FDA-approved drugs for treating PTSD, and c) one of the two most effective SSRIs for major depression, a common comorbidity with PTSD. Dosing will follow clinical practice guidelines, i.e., doses will be chosen based on clinical response and tolerability.

Description Of Administration Of Drug: The investigators are using an approach , which represents enhanced clinical care in that participants discuss medication levels, side effects, and symptoms with a psychiatrist every two weeks. Study medication and placebo will be stored and distributed by VA Boston Pharmacy service.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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:

    * information about the design of the study, inclusion and exclusion criteria, the participant's psychiatric and medical diagnoses as well as illness severity, as assessed in the screening evaluation, and any history of safety issues such as risk to self or others.
    * If the participant doesn't sign a release of release of information (ROI) to contact the provider, the participant will not be entered into the active study.

Primary outcomes:
measure: Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Change
timeFrame: Administered at screening session 1, and weeks 0, 2, 6, and 14
Secondary outcomes:
measure: Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) Change
timeFrame: Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14
measure: Hamilton Depression Rating Scale (HAM-D) Change
timeFrame: Administered at weeks 0, 2, 6 and 14
measure: Depression Anxiety Stress Scales (DASS-21) Change
timeFrame: Administered at screening session 1, and weeks 0, 2, 6, and 14
measure: PTSD Checklist for DSM-5 (PCL-5) Change
timeFrame: Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14
measure: The Positive and Negative Affect Schedule (PANAS) Change
timeFrame: Administered at screening session 1, and weeks 0, 2, 6, and 14
measure: Symptom Checklist (SCL-90-R) Change
timeFrame: Administered at screening session 1, and weeks 0, 2, 6, and 14
Other outcomes:
Locations:
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center, Charleston, SC
state: South Carolina
Study officials:
affiliation: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
name: Suzanne Pineles, PhD
role: PRINCIPAL_INVESTIGATOR
References: