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University of Iowa Interventional Psychiatry Service Patient Registry

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04480918
Recruitment Status : Recruiting
First Posted : July 22, 2020
Last Update Posted : April 8, 2021
Sponsor:
Information provided by (Responsible Party):
Mark Niciu, University of Iowa

Brief Summary:
The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD). 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").

Condition or disease Intervention/treatment
Treatment Resistant Depression Major Depressive Episode Major Depression Major Depressive Disorder Bipolar Disorder Bipolar Depression Device: Electroconvulsive Therapy (ECT) Device: Transcranial Magnetic Stimulation (TMS) Drug: Ketamine Drug: Esketamine

Detailed Description:

Treatment response biomarkers in TRD 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 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.

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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Months
Official Title: University of Iowa Interventional Psychiatry Service Patient Registry
Actual Study Start Date : November 2, 2020
Estimated Primary Completion Date : August 2050
Estimated Study Completion Date : August 2050

Resource links provided by the National Library of Medicine


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.
Device: Electroconvulsive Therapy (ECT)
ECT for the treatment of treatment-resistant depression in an active major depressive episode

Device: Transcranial Magnetic Stimulation (TMS)
TMS for the treatment of treatment-resistant depression in an active major depressive episode

Drug: Ketamine
Intravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode

Drug: Esketamine
Intranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode




Primary Outcome Measures :
  1. 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). ]
    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.


Secondary Outcome Measures :
  1. 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).

  2. 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."

  3. 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.

  4. 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."

  5. 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.


Other Outcome Measures:
  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.


Biospecimen Retention:   Samples With DNA
blood, saliva and cheek swabs for epi/genetic expression


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 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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. 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, 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.
Criteria

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 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

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): NCT04480918


Contacts
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Contact: Alexandra A Alario, B.S. 319-384-8470 alexandra-alario@uiowa.edu
Contact: Benjamin D Pace, M.S. 319-384-9302 benjamin-pace@uiowa.edu

Locations
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United States, Iowa
University of Iowa Health Care Recruiting
Iowa City, Iowa, United States, 52242
Contact: Benjamin Pace, M.S.    319-384-9302    benjamin-pace@uiowa.edu   
Contact: Sage M Comstock, M.A.    319-353-8536    sage-comstock@uiowa.edu   
Principal Investigator: Mark J Niciu, M.D. Ph.D.         
Sponsors and Collaborators
Mark Niciu
Investigators
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Principal Investigator: Mark J Niciu, M.D., Ph. D. University of Iowa
Publications:

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Responsible Party: Mark Niciu, Assistant Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT04480918    
Other Study ID Numbers: 202003055
First Posted: July 22, 2020    Key Record Dates
Last Update Posted: April 8, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Mark Niciu, University of Iowa:
Electroconvulsive Therapy
Transcranial Magnetic Stimulation
Ketamine
Esketamine
Additional relevant MeSH terms:
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Disease
Depression
Depressive Disorder
Depressive Disorder, Major
Bipolar Disorder
Depressive Disorder, Treatment-Resistant
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Ketamine
Esketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents
Psychotropic Drugs