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Predicting SSRI Efficacy in Veterans With PTSD (SSRI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04183205
Recruitment Status : Active, not recruiting
First Posted : December 3, 2019
Last Update Posted : May 11, 2020
Sponsor:
Collaborators:
Middlebury College
Suffolk University
Massachusetts General Hospital
Information provided by (Responsible Party):
VA Office of Research and Development

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) are most likely to show a positive response to selective serotonin reuptake inhibitor (SSRI) medications. Participants will be recruited over approximately 3.25 years, until at least 94 participants complete the 17 week study.

Condition or disease Intervention/treatment Phase
Posttraumatic Stress Disorder Diagnostic Test: LDAEP Drug: Placebo Drug: sertraline Phase 4

Detailed Description:

Due to the COVID-19 pandemic, and after consultation with research oversight entities, recruitment has been placed on temporary admin hold as of 3/17/2020

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.

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 reliability of LDAEP and 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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.
Masking: Double (Participant, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Screening
Official Title: An Electrophysiological Predictor of SSRI Response in Veterans With PTSD
Actual Study Start Date : September 11, 2019
Estimated Primary Completion Date : March 30, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo only arm
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
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.

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

Active Comparator: Sertraline arm
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
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.

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

Drug: sertraline
Sertraline is an FDA approved SSRI for treatment of PTSD.
Other Name: zoloft




Primary Outcome Measures :
  1. Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Change [ Time Frame: Administered at screening session 1, and weeks 0, 2, 6, and 14 ]
    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.


Secondary Outcome Measures :
  1. Quick Inventory of Depressive Symptomatology- Self Report (QIDS-SR) Change [ Time Frame: Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14 ]
    The QIDS-SR will be used to measure the severity of depressive symptoms. The QIDS provides equivalent weightings (0-3) for each symptom item, gives clearly stated anchors that estimate the frequency and severity of symptoms, and includes all items required to diagnose a major depressive episode.

  2. Hamilton Depression Rating Scale (HAM-D) Change [ Time Frame: Administered at weeks 0, 2, 6 and 14 ]
    The HAM-D is the most widely used clinician-administered scale for assessing severity of depression symptoms. The 6-item unidimensional core Melancholia subscale of the HAM-D will be used as the primary depression outcome variable.

  3. Depression Anxiety Stress Scales (DASS-21) Change [ Time Frame: Administered at screening session 1, and weeks 0, 2, 6, and 14 ]
    DASS-21 is a 21-item measure that assesses the severity of a range of symptoms common to depression, anxiety, and stress. The total score can be used as a measure of general distress or depression, anxiety, and stress subscales can be scored separately.

  4. PTSD Checklist for DSM-5 (PCL-5) Change [ Time Frame: Administered at screening session 1, and weeks 0, 2, 4, 6, 8, 10, 12, and 14 ]
    The PCL-5 is a 20-item measure that assesses DSM-5 symptoms of PTSD. Participants will rate how much they experienced each symptom on a 5-point Likert-type scale (0 = "not at all" to 4 = "extremely") during the past week (total range=0-80). The PCL-5 will be anchored to participants' worst traumatic event. In addition to the administration of these measures during the four assessment sessions, the PCL-5 will also be administered bi-weekly at each psychiatrist check-in visit.

  5. The Positive and Negative Affect Schedule (PANAS) Change [ Time Frame: Administered at screening session 1, and weeks 0, 2, 6, and 14 ]
    The PANAS consists of two, 10-item mood scales that measure positive (e.g., 'enthusiastic') and negative (e.g., 'upset') affect separately.

  6. Symptom Checklist (SCL-90-R) Change [ Time Frame: Administered at screening session 1, and weeks 0, 2, 6, and 14 ]
    SCL-90-R measures the following nine primary psychiatric symptom dimensions: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. The Global Severity Index (GSI) is the average rating given to all 90 items and provides a measure of general psychopathology.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • meeting diagnostic criteria for PTSD as defined by DSM-5
  • study psychiatrist's judgment that SSRIs are an acceptable treatment option for participants' presenting concerns
  • 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04183205


Locations
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United States, Massachusetts
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, United States, 02130
Sponsors and Collaborators
VA Office of Research and Development
Middlebury College
Suffolk University
Massachusetts General Hospital
Investigators
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Principal Investigator: Suzanne Pineles, PhD VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT04183205    
Other Study ID Numbers: MHBB-028-17F
First Posted: December 3, 2019    Key Record Dates
Last Update Posted: May 11, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: A de-identified, anonymized dataset will be created and shared after study completion.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Data will be available within a year of submission of the final report.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by VA Office of Research and Development:
Treatment
Posttraumatic Stress Disorder (PTSD)
selective serotonin re-uptake inhibitor (SSRI)
loudness dependence of auditory evoked potentials
Electrophysiology
Additional relevant MeSH terms:
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Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Trauma and Stressor Related Disorders
Mental Disorders
Sertraline
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs