Combination of Novel Therapies for CKD Comorbid Depression
Status:
Recruiting
Trial end date:
2026-04-01
Target enrollment:
Participant gender:
Summary
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
non-dialysis 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.
Phase:
Phase 2
Details
Lead Sponsor:
University of Texas Southwestern Medical Center
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) University of Washington