University of Iowa Interventional Psychiatry Service Patient Registry

May 8, 2023 updated by: Mark Niciu
The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and autonomic nervous system measures (i.e. "fight-or-flight" response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient ("personalized medicine").

Study Overview

Detailed Description

Treatment response biomarkers in TRD and OCD have been and will remain an active area of research. Interventional treatments in psychiatry, e.g. ECT, TMS, racemic ketamine infusions and intranasal esketamine insufflations, offer exciting opportunities for biomarker discovery due their procedural nature (obviating concerns for treatment non-adherence in non-supervised settings), more rapid-onset, and larger effect sizes than typically seen with traditional antidepressant medications or evidence-based psychotherapies. Although no well-replicated TRD biomarkers have been approved for standard clinical use, several potential biomarkers have been investigated across multiple modalities, i.e. neuroimaging(1,2), autonomic function(3,4), genetics(5-7), electroencephalography (EEG) (8,9), and computational analysis of behavior or speech(10). These studies have promising early results but often insufficient predictive power at the subject-level. The investigators anticipate that combinatorial, multimodal biomarkers will enhance predictive power and, as a result, improve treatment personalization in major depression.

The University of Iowa Interventional Psychiatry Service Patient Registry systematically collects data from TRD and OCD patients undergoing procedural treatment(s) for major depression. First, the investigators seek to replicate and/or extend discoveries from prior investigations, e.g. TMS-induced autonomic changes as positive predictors of antidepressant efficacy. The investigators will also compare and contrast differences, not only in response to a given therapy, but also how individual subjects respond across different treatment modalities, e.g. how does functional connectivity in the brain change in response to an effective course of TMS as opposed to ECT? Such findings could inform the future development of clinical guidelines; this is especially critical as some of these treatment modalities have only recently been approved for TRD by the U.S. Food and Drug Administration, e.g. intermittent theta burst stimulation (iTBS) and intranasal esketamine insufflation and dTMS for OCD.

Next, a longitudinal database may also be valuable for future biomarker discovery and/or replication in independent samples, i.e. an epigenetic signature of antidepressant treatment response to an interventional modality identified by another research group. Similarly, this patient registry could be valuable for collaborative research with other institutions administering interventional treatments in psychiatry.

Study Type

Observational

Enrollment (Anticipated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Health Care
        • Contact:
        • Principal Investigator:
          • Mark J Niciu, M.D. Ph.D.
        • Principal Investigator:
          • Nicholas T Trapp, M.D. M.S.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 97 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients (18-99 years old) in a current major depressive episode in the context of major depressive disorder (MDD) or bipolar disorder (BD) will be recruited for this protocol. Adult patients received TMS for OCD will also be recruited. All treatment will be in addition to the patient's clinical care with the University of Iowa's Interventional Psychiatry Service for treatment-resistant major depression or OCD, and the decision to participate, withdraw from participation or not participate will if not affect clinical care decision-making. We appreciate that minority groups tend to be underrepresented in neuropsychiatric research studies. Therefore, we will make a concerted effort to keep the proportion of racial/ethnic minorities recruited consistent with the demographics of the surrounding communities.

Description

INCLUSION CRITERIA:

  1. 18-99 years of age
  2. English-speaker with a level of understanding sufficient to agree to clinical treatment with a treatment modality offered by the Interventional Psychiatry Service, all required research procedures, and sign an informed consent document
  3. Clinical diagnosis of a major depressive episode in the context of major depressive disorder or bipolar disorder or treatment-resistant OCD evaluated by a provider on the Interventional Psychiatry Service and felt to be an appropriate candidate for clinical treatment with a treatment modality offered by the Interventional Psychiatry Service.

EXCLUSION CRITERIA:

  1. Age less than 18 years
  2. A primary neuropsychiatric diagnosis that is not either major depressive disorder or bipolar disorder
  3. Serious, unstable medical conditions/problems including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, e.g. uncontrolled asthma, uncontrolled hyper/hypothyroidism or active cancer.
  4. Involuntary commitment to psychiatry inpatient units
  5. If patients have one or more of the following MRI Exclusion criteria, they will not be able to participate in those aspects of this study:

    1. The presence of an implanted device including pacemaker, coronary stent, defibrillator, or neurostimulation device that is not MRI-compatible
    2. The presence of ferromagnetic objects in the body, i.e. bullets, shrapnel, and/or metal slivers
    3. Clinically-significant claustrophobia
    4. Clinically-significant hearing loss
    5. Pregnant or nursing women or women of child bearing potential not using at least one medically accepted means of contraception (to include oral, injectable, or implant birth control, condom or diaphragm with spermicide, intrauterine devices (IUD), tubal ligation, abstinence, or partner with vasectomy)
    6. The presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Major Depressive Episode
After referral to the University of Iowa's Interventional Psychiatry Clinic, the patient will be clinically evaluated and, if appropriate, commence the procedural-based treatment course.
ECT for the treatment of treatment-resistant depression OR Bipolar Disorder in an active major depressive episode
TMS for the treatment of treatment-resistant depression in an active major depressive episode
Intravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode
Intranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode
TMS for the treatment of OCD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
For patients with TRD, the MADRS will be administered. The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Yale-Brown Obsessive Compulsive Scale
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
For patients with OCD, the YBOCS will be administered. Questions on the YBOCS examine the amount of time spent thinking and acting on obsessions and compulsions, how much impairment or distress is caused, and how much resistance and control the participant has over their thoughts or behavior.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Global Impression/Severity (CGI) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of "not assessed." Item 3 is rated on a 4-point Likert scale from "none" to "outweighs therapeutic effect." Items 1 and 3 are assessed in relation to last clinical encounter (if possible).
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Generalized Anxiety Disorder, 7-item (GAD-7) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The GAD-7 is the self-reported anxiety questionnaire which scores each of the 7 symptoms of Generalized Anxiety Disorder in the last two weeks on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("over half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Montreal Cognitive Assessment (MoCA) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The MoCA is a 30-point screening instrument for detecting cognitive dysfunction. It is used to assess the following cognitive domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed (short-term memory recall), and orientation.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Patient Health Questionnaire, 9-item (PHQ-9) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The PHQ-9 is the self-reported depression module of the PHQ, which scores each of the 9 symptoms of a major depressive episode on a 4-point scale, i.e. 0 ("not at all"), 1 ("several days"), 2 ("more than half the days") and 3 ("nearly every day"). Functional impairment is also assessed from "Not difficult at all" to "Extremely difficult."
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Temperament and Character Inventory (TCI) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The TCI is a 240-item questionnaire. It operates with seven dimensions of personality traits, i.e. four so-called temperaments: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS), and three so-called characters: Self-Directedness (SD), Cooperativeness (CO) and Self-Transcendence (ST). Each of these traits has a varying number of subscales.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Actigraphy Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The patient will be asked to continuously wear a Fitbit wristband to monitor gross motor activity, e.g. foot steps. Changes in gross motor activity throughout the day will also provide data on circadian rhythmicity (sleep-wake cycles).
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Candidate Gene (DNA) Polymorphisms
Time Frame: The genetic specimen will be obtained within approximately 1 week of starting treatment (likely with the baseline epigenetic sample.
The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, and DNA will be isolated and extracted. Data on genetic polymorphisms (differences) that have been demonstrated or hypothesized to play a functional role in major depression, e.g. the brain derived neurotrophic factor (BDNF) rs6265 (val66met) single nucleotide polymorphism, will be obtained. These genotypes (genetic data) will then be correlated with antidepressant response.
The genetic specimen will be obtained within approximately 1 week of starting treatment (likely with the baseline epigenetic sample.
Electroencephalography (EEG) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The investigators will obtain task-free ("resting state") rs-EEG [detecting electrical signals in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Epigenetic (Experience-Based) DNA Modifications Pre-Post Change
Time Frame: The initial specimen will be obtained within approximately 1 week of starting treatment. The post-specimen will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The investigators will obtain tissue samples, e.g. blood, saliva, and/or cheek swabs, at baseline and in response to interventional treatments for treatment-resistant depression. DNA will be isolated and extracted. Data on epigenetic (experience-based) modifications to the DNA that have been demonstrated or hypothesized to play a functional role in major depression, e.g. global methylation changes, will be obtained. Changes in epigenetic status, e.g. global DNA methylation changes pre- and post-treatment, will then be correlated with antidepressant response.
The initial specimen will be obtained within approximately 1 week of starting treatment. The post-specimen will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Facial Expression Analysis Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Facial recognition software, FaceX (FaceX LLC) will be used to record and analysis facial features at rest and evoked by interview questions and emotionally provocative videos.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Galvanic Skin Response Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Galvanic skin response as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Heart Rate Variability Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Heart rate variability as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
National Institutes of Health (NIH) Toolbox(R) Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
The NIH Toolbox is a comprehensive set of neurobehavioral assessments that assess multiple neuropsychiatric domains. We will perform the cognitive and emotional batteries in this study.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Pupillometry Pre-Post Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Pupillometry (pupil diameter measurements) as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later).
Resting State Functional Magnetic Resonance Imaging (rs-fMRI) Pre-Post Change
Time Frame: The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).
The investigators will obtain task-free ("resting state") rs-fMRI [detecting blood oxygen-level dependent (BOLD) signal in the brain] at baseline and in response to interventional treatments for treatment-resistant depression.
The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).
Structural Magnetic Resonance Imaging (MRI) Pre-Post Change
Time Frame: The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).
The investigators will obtain structural brain imaging at baseline and in response to interventional treatments for treatment-resistant depression.
The initial imaging session will be obtained within approximately 1 week of starting treatment. The post-treatment imaging session occur as close as possible following completion of treatment course (usually 4-6 weeks later).
Vocal Pattern Detection Pre, During and Post-Change
Time Frame: Pre-assessment will be obtained within approximately 1 week of starting treatment. Interim assessments will occur weekly during treatment. Post-assessment will be obtained as close as possible following completion of treatment course.
The patient will be asked to read standardized passages, i.e. Grandfather Passage and Rainbow Passage, and answer questions about daily life and interests while being recorded. These recordings will be transcribed and analyzed for vocal tone, inflection, word choice, etc.
Pre-assessment will be obtained within approximately 1 week of starting treatment. Interim assessments will occur weekly during treatment. Post-assessment will be obtained as close as possible following completion of treatment course.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Mark J Niciu, M.D., Ph. D., University of Iowa
  • Principal Investigator: Nicholas T Trapp, M.D., M.S., University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 2, 2020

Primary Completion (Anticipated)

August 1, 2050

Study Completion (Anticipated)

August 1, 2050

Study Registration Dates

First Submitted

July 2, 2020

First Submitted That Met QC Criteria

July 16, 2020

First Posted (Actual)

July 22, 2020

Study Record Updates

Last Update Posted (Actual)

May 9, 2023

Last Update Submitted That Met QC Criteria

May 8, 2023

Last Verified

May 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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