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.
University of Iowa Interventional Psychiatry Service Patient Registry
Brief Summary
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").
Intervention / Treatment
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Electroconvulsive Therapy (ECT) (DEVICE)ECT for the treatment of treatment-resistant depression OR Bipolar Disorder in an active major depressive episode
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Transcranial Magnetic Stimulation (TMS) (DEVICE)TMS for the treatment of treatment-resistant depression in an active major depressive episode
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Ketamine (DRUG)Intravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode
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Esketamine (DRUG)Intranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode
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Deep Transcranial Magnetic Stimulation (dTMS) (DEVICE)TMS for the treatment of OCD
Condition or Disease
- Treatment Resistant Depression
- Major Depressive Episode
- Major Depression
- Major Depressive Disorder
- Bipolar Disorder
- Bipolar Depression
- Obsessive-Compulsive Disorder
Phase
Study Design
| Study type: | OBSERVATIONAL |
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| Status: | Recruiting |
| Study results: | No Results Available |
| Age: | 18 Years to 99 Years |
| Enrollment: | 1000 (ESTIMATED) |
| Funded by: | Other |
| Time Perspective: | Prospective |
| Observational Model: | Cohort |
Masking |
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Clinical Trial Dates
| Start date: | Nov 02, 2020 | ACTUAL |
|---|---|---|
| Primary Completion: | Aug 01, 2050 | ESTIMATED |
| Completion Date: | Aug 01, 2050 | ESTIMATED |
| Study First Posted: | Jul 22, 2020 | ACTUAL |
| Results First Posted: | Aug 31, 2020 | |
| Last Updated: | May 08, 2023 |
Sponsors / Collaborators
Lead Sponsor:
Mark Niciu
Responsible Party:
Mark Niciu
Location
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.
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.
Participant Groups
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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.
Eligibility Criteria
| Sex: | All |
|---|---|
| Minimum Age: | 18 |
| Maximum Age: | 99 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
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
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
This clinical trial is recruiting
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Primary Outcomes
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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.
Secondary Outcomes
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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).
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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."
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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.
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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."
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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 Outcomes
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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).
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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.
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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.
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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.
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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.
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Galvanic skin response as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
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Heart rate variability as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
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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.
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Pupillometry (pupil diameter measurements) as a surrogate marker of autonomic reactivity will be obtained in response to the presentation of emotional stories or images.
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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.
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The investigators will obtain structural brain imaging at baseline and in response to interventional treatments for treatment-resistant depression.
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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.
More Details
| NCT Number: | NCT04480918 |
|---|---|
| Other IDs: | 202003055 |
| Study URL: | https://clinicaltrials.gov/study/NCT04480918 |
Last updated: Sep 29, 2023