- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04422652
Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)
Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Aim 1. Compare the efficacy and tolerability of two 16-week strategies vs. control for treatment of CKD patients with MDD starting with (1) BAT or (2) bupropion, each augmented to a combination of both in non-remitters. Primary hypothesis: Treatment with either strategy will improve depression (primary endpoint) and be tolerable.
Patients with non-dialysis stages 3b-5 CKD and MDD (N=201) will be randomized 1:1:1 to 16 weeks of:
Strategy 1: Single-blind BAT plus placebo, augmented in non-remitters at 8 weeks with single-blind bupropion; Strategy 2: Double-blind bupropion plus single-blind Clinical Management (CM) attention control, augmented in non-remitters at 8 weeks with single-blind BAT; Control: CM attention control plus placebo. There will be >80% power to detect a minimal clinically important difference (MCID) of 2 points on the Quick Inventory of Depressive Symptomatology between each intervention and control, assuming a 14% attrition rate.
Exploratory aim (a): Explore if remote access to therapy via internet vs. travel to clinic affects treatment efficacy.
Aim 2. Investigate efficacy and tolerability of 8 weeks (Phase 1) of (1) BAT plus placebo or (2) bupropion plus CM, vs. control, for improvement in depression. Secondary hypothesis: Treatment with 8 weeks of BAT or bupropion will improve depression. There will be 80% power to detect a MCID of 2 points between each arm and control, assuming 10% attrition.
Exploratory aims:
(a) Investigate whether patient preference for BAT vs. drug affects treatment efficacy; (b) compare efficacy of each combination in Phase 2 with control; (c) compare change from baseline in plasma C-reactive protein in drug vs. BAT or control arms.
Aim 3. Investigate the efficacy of these two 16-week treatment strategies vs. control for improvement in CKD patient-centered outcomes including: (a) adherence to medications and healthcare visits; (b) fatigue; (c) sleep; (d) overall functioning. Secondary hypothesis: Treatment with either strategy will result in clinically meaningful improvements in adherence, fatigue, sleep and overall functioning in patients with CKD.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Meredith McAdams, MD
- Phone Number: 214-645-5418
- Email: Meredith.McAdams@UTSouthwestern.edu
Study Locations
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New York
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Stony Brook, New York, United States, 11794-8430
- Not yet recruiting
- Stony Brook University Medical Center
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Texas
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Dallas, Texas, United States, 75235
- Recruiting
- Parkland Health and Hospital System
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Dallas, Texas, United States, 75390
- Recruiting
- UT Southwestern and Affiliates
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Washington
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Seattle, Washington, United States, 98195
- Recruiting
- University of Washington
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female adults aged 18 years or greater. There will be no upper age limit.
- Presence of CKD stages 3b, 4 or non-dialysis stage 5, with an estimated glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 for a period of at least 3 months, as defined by the National Kidney Foundation and determined using the four-variable Modification of Diet for Renal Diseases Study formula.
- Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria
- Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization.
- Able to understand and sign informed consent after the nature of the study has been fully explained
- Kidney transplant patients that are at least 6 month post-transplantation (3 months post-transplant, with at least another 3 months to confirm eGFR <45)
Exclusion Criteria:
- Unable to understand or give informed consent.
- Unwilling or unable to participate in the protocol or comply with any of its components
- Receiving chronic dialysis
- Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal
- Terminal chronic obstructive pulmonary disease or cancer
- Presence of seizure disorder
- Current use of class I anti-arrhythmic medications (such as 1C propafenone and flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants
- Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort.
- Use of medications known to cause QT prolongation on EKG
- Ongoing use of antidepressant medications for depression treatment
- Past treatment failure on bupropion
- Initiation of depression-focused psychotherapy in the 3 months prior to study entry
- Active alcohol or substance abuse or dependence that requires acute detoxification at study entry
- Present or past psychosis or Bipolar I or II disorder
- Dementia or a Mini-Mental State Examination score <23
- Active suicidal intent
- Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Strategy 1
Strategy 1: Single-blind Behavioral Activation Therapy plus placebo for 8 weeks (Phase 1), augmented in non-remitters at 8 weeks with single-blind bupropion (Phase 2) for another 8 weeks.
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Brief behavioral activation treatments administered via video tele-conferencing.
Double-blind placebo.
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Active Comparator: Strategy 2
Strategy 2: Double-blind bupropion plus single-blind Clinical Management (CM) attention control for 8 weeks (Phase 1), augmented in non-remitters at 8 weeks with single-blind BAT (Phase 2) for another 8 weeks.
|
Bupropion is an anti-depressant medication.
Other Names:
Clinical management will serve as the attention control for the Behavioral Activation Therapy intervention.
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Placebo Comparator: Control
Control: Clinical management attention control plus placebo for 16 weeks
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Double-blind placebo.
Clinical management will serve as the attention control for the Behavioral Activation Therapy intervention.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)
Time Frame: Assessed at baseline and weeks 4, 6, 8, 12, and 16
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Assess the change from baseline in the QIDS-C total score in each of the intervention arms vs. the control arm.
The score on the QIDS-C ranges from 0-27, with higher scores indicating more severe depressive symptoms.
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Assessed at baseline and weeks 4, 6, 8, 12, and 16
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serious adverse events
Time Frame: Assessed at weeks 4, 6, 8, 12, and 16.
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Pre-specified serious adverse events include death, hospitalization, renal replacement therapy (dialysis or kidney transplantation), and acute suicidal intent.
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Assessed at weeks 4, 6, 8, 12, and 16.
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Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)
Time Frame: Assessed at baseline and weeks 4, 6, and 8.
|
Assess the change from baseline in the QIDS-C total score in each of the intervention arms vs. the control arm during the first 8 weeks of the study when participants in the treatment arms will be receiving monotherapy with BAT or bupropion.
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Assessed at baseline and weeks 4, 6, and 8.
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Serious adverse events with monotherapy
Time Frame: Assessed at weeks 4, 6, and 8.
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Pre-specified serious adverse events include death, hospitalization, renal replacement therapy (dialysis or kidney transplantation), and acute suicidal intent during the first 8 weeks of the study.
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Assessed at weeks 4, 6, and 8.
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Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)
Time Frame: Assessed at weeks 8, 12, and 16.
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Assess the change from baseline in the QIDS-C total score in each of the intervention arms vs. the control arm during the second 8 weeks of the study when participants who did not respond to the treatment arms will be receiving combination therapy with BAT and bupropion.
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Assessed at weeks 8, 12, and 16.
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High sensitivity C-reactive protein
Time Frame: Assessed at baseline and week 8
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Change from baseline to Week 8 in the plasma level of high sensitivity C-reactive protein (hsCRP) in the intervention groups vs. control.
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Assessed at baseline and week 8
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Adherence to medications by Pill Count
Time Frame: Assessed at weeks 4, 8, 12, and 16.
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The proportion of participants in each arm that are adherent to antidepressant medications (or placebo, prescribed in the setting of the clinical trial).
Adherence will be defined as 80% or greater of study drug taken.
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Assessed at weeks 4, 8, 12, and 16.
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Fatigue assessed by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale
Time Frame: Assessed at baseline and weeks 4, 8, 12, and 16
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Change from baseline in the FACIT-F scale in the intervention groups vs. control.
The FACIT has 13 items, each on a Likert scale, with a score range of 0-52, and higher scores indicating a lower level of fatigue.
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Assessed at baseline and weeks 4, 8, 12, and 16
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Sleep assessed by the Insomnia Severity Index (ISI)
Time Frame: Assessed at baseline and weeks 4, 8, 12, and 16
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Change from baseline in the Insomnia Severity Index (ISI) in the intervention groups vs. control.
The ISI has 7 items that measure insomnia severity, with higher scores indicating more severe insomnia.
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Assessed at baseline and weeks 4, 8, 12, and 16
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Overall functioning assessed by the Sheehan Disability Scale (SDS)
Time Frame: Assessed at baseline and weeks 4, 8, 12, and 16
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Change from baseline in the SDS in the intervention groups vs. control groups.
The SDS assesses functional impairment in 3 domains: work, social life, and family, each evaluated on a 10-point visual analog scale, which are summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).
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Assessed at baseline and weeks 4, 8, 12, and 16
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Susan Hedayati, MD, University of Texas
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Mood Disorders
- Urologic Diseases
- Disease Attributes
- Renal Insufficiency
- Chronic Disease
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Depressive Disorder
- Kidney Diseases
- Renal Insufficiency, Chronic
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Dopamine Uptake Inhibitors
- Bupropion
Other Study ID Numbers
- STU-2020-0046
- R01DK124379 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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