Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 201
- 试验地点
- 4
- 主要终点
- Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)
研究概览
简要总结
The overall goal of the study is to determine if treatment of a Major Depressive Disorder (MDD) improves the outcomes of patients with chronic kidney disease (CKD). We showed that MDD is present in 25% of CKD patients and independently associated with progression to End-Stage Kidney Disease, hospitalization, and death. Depression is also associated with lower quality of life (QOL), fatigue, poor sleep, and non-adherence to diet and medications. However, evidence for efficacy and tolerability of commonly-used antidepressant medications or nonpharmacologic treatments are limited in CKD patients. Our group was the first to conduct a double-blind randomized controlled trial for MDD treatment in 201 patients with non-dialysis CKD, and showed that sertraline, a commonly used selective serotonin reuptake inhibitor (SSRI), was no more efficacious than placebo for improving depressive symptoms. It becomes imperative to test novel strategies to treat MDD in CKD. We propose to compare with a control group, the efficacy and tolerability of two novel treatment strategies - (1) Behavioral Activation Teletherapy (BAT) for 16 weeks, with the addition of bupropion, a non-SSRI antidepressant, at 8 weeks for patients whose depression has not remitted (non-remitters); and (2) bupropion for 16 weeks, with the addition of BAT at 8 weeks for non-remitters. In Aim 1, we will investigate the efficacy and tolerability of these 2 strategies vs. control for improvement in a primary endpoint of depressive symptoms in 201 patients (67 per group) with CKD stages 3b-5 and MDD at 2 sites, randomized 1:1:1 to either strategy or a control group of Clinical Management plus placebo. We hypothesize that either approach vs. control will result in a minimal clinically important difference of 2 points improvement in depressive symptoms, as ascertained blindly by the Quick Inventory of Depressive Symptomatology. In Aim 2 we will investigate the efficacy and tolerability of 8 weeks of (1) single-blind BAT plus placebo or (2) double-blind bupropion plus Clinical Management vs. control for improvement in depressive symptoms. In Aim 3, we will compare the efficacy of these 2 treatments strategies vs. control for improvement in CKD patient-centered outcomes including a. adherence to medications and healthcare visits; b. fatigue; c. sleep; and d. overall functioning. A clinical trial is urgently needed to address the evidence gap that exists for MDD treatment in CKD patients.
详细描述
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 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Those eligible will be randomized via a computerized random number generator 1:1:1 to BAT, bupropion, or control, using block randomization, stratified by site and CKD stage (3b, 4, 5-non dialysis, and 5-dialysis). Randomization assignment will be obtained via the secure web portal hosted at UTSW. As in previous trials that involve therapy for MDD, it is challenging to double-blind aspects of this study that involve BAT. However, we have made every effort to maintain blind as much as possible. Bupropion for Strategy 2 and double-blind matching placebo for the control arm will be administered by concealed allocation. Participants in Strategy 1 will receive matching placebo by single-blind allocation. Although it is impossible to conceal the allocation of the BAT to the research team, it is intended for the participants to remain single-blinded to BAT vs. CM. Using Computer Assisted Telephone Interviewing, the same assessor, blinded to interventions, will assess outcomes for both sites.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female adults aged 18 years or greater. There will be no upper age limit.
- •Presence of CKD stages 3b, 4 or 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)
排除标准
- •Unable to understand or give informed consent.
- •Unwilling or unable to participate in the protocol or comply with any of its components
- •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
研究组 & 干预措施
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.
干预措施: Placebo (Drug)
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.
干预措施: Clinical Management (Other)
Control
Control: Clinical management attention control plus placebo for 16 weeks
干预措施: Clinical Management (Other)
Control
Control: Clinical management attention control plus placebo for 16 weeks
干预措施: Placebo (Drug)
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.
干预措施: Behavioral activation therapy (Behavioral)
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.
干预措施: Bupropion (Drug)
结局指标
主要结局
Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)
时间窗: Assessed at baseline and weeks 4, 6, 8, 12, and 16
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.
次要结局
- Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)(Assessed at baseline and weeks 4, 6, and 8.)
- Serious adverse events(Assessed at weeks 4, 6, 8, 12, and 16.)
- Serious adverse events with monotherapy(Assessed at weeks 4, 6, and 8.)
- High sensitivity C-reactive protein(Assessed at baseline and week 8)
- Sleep assessed by the Insomnia Severity Index (ISI)(Assessed at baseline and weeks 4, 8, 12, and 16)
- Adherence to medications by Pill Count(Assessed at weeks 4, 8, 12, and 16.)
- Fatigue assessed by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale(Assessed at baseline and weeks 4, 8, 12, and 16)
- Overall functioning assessed by the Sheehan Disability Scale (SDS)(Assessed at baseline and weeks 4, 8, 12, and 16)
- Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)(Assessed at weeks 8, 12, and 16.)
研究者
Susan Hedayati, MD
PROFESSOR, IM-Nephrology
Stony Brook University