Combination of Novel Therapies for CKD Comorbid Depression

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: Chronic Kidney Diseases, Major Depressive Disorder, End Stage Kidney Disease (ESRD)

In brief

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.

Key facts

Study ID: NCT04422652
Run by: Stony Brook University
People needed: 201
Starts: 2020-09-24
Expected to finish: 2027-04-01
Last updated by the study team: 2025-11-28

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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)

You may not qualify if…

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

Where it is running

Parkland Health and Hospital System — Dallas, Texas, United States (enrolling)
UT Southwestern and Affiliates — Dallas, Texas, United States (enrolling)
University of Washington — Seattle, Washington, United States (enrolling)
Stony Brook University Medical Center — Stony Brook, New York, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.