Combination of Novel Therapies for CKD Comorbid Depression

NCT ID: NCT04422652

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-24
• Study Completion Date: 2027-04-01

Brief 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 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.

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 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.

Conditions

Chronic Kidney Diseases; Major Depressive Disorder; End Stage Kidney Disease (ESRD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Behavioral activation therapy

Intervention Type: BEHAVIORAL

Brief behavioral activation treatments administered via video tele-conferencing.

Placebo

Intervention Type: DRUG

Double-blind placebo.

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.

Group Type: ACTIVE_COMPARATOR

Bupropion

Intervention Type: DRUG

Bupropion is an anti-depressant medication.

Clinical Management

Intervention Type: OTHER

Clinical management will serve as the attention control for the Behavioral Activation Therapy intervention.

Control

Control: Clinical management attention control plus placebo for 16 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Double-blind placebo.

Clinical Management

Intervention Type: OTHER

Clinical management will serve as the attention control for the Behavioral Activation Therapy intervention.

Interventions

Bupropion

Bupropion is an anti-depressant medication.

Intervention Type: DRUG

Behavioral activation therapy

Brief behavioral activation treatments administered via video tele-conferencing.

Intervention Type: BEHAVIORAL

Placebo

Double-blind placebo.

Intervention Type: DRUG

Clinical Management

Clinical management will serve as the attention control for the Behavioral Activation Therapy intervention.

Intervention Type: OTHER

Other Intervention Names

Wellbutrin

Eligibility Criteria

Inclusion Criteria

1. Male or female adults aged 18 years or greater. There will be no upper age limit.

2. 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.

3. Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria

4. Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization.

5. Able to understand and sign informed consent after the nature of the study has been fully explained

6. 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

1. Unable to understand or give informed consent.

2. Unwilling or unable to participate in the protocol or comply with any of its components

3. Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal

4. Terminal chronic obstructive pulmonary disease or cancer

5. Presence of seizure disorder

6. 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

7. Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort.

8. Use of medications known to cause QT prolongation on EKG

9. Ongoing use of antidepressant medications for depression treatment

10. Past treatment failure on bupropion

11. Initiation of depression-focused psychotherapy in the 3 months prior to study entry

12. Active alcohol or substance abuse or dependence that requires acute detoxification at study entry

13. Present or past psychosis or Bipolar I or II disorder

14. Dementia or a Mini-Mental State Examination score <23

15. Active suicidal intent

16. Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Stony Brook University

OTHER

Sponsor Role: lead

Responsible Party

Susan Hedayati, MD

PROFESSOR, IM-Nephrology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan Hedayati, MD

Role: PRINCIPAL_INVESTIGATOR

Stony Brook University

Locations

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status: NOT_YET_RECRUITING

Parkland Health and Hospital System

Dallas, Texas, United States

Site Status: RECRUITING

UT Southwestern and Affiliates

Dallas, Texas, United States

Site Status: RECRUITING

University of Washington

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Meredith McAdams, MD

Role: CONTACT

Meredith.McAdams@UTSouthwestern.edu

214-645-5418

Ana Arroyo

Role: CONTACT

ana.arroyo@utsouthwestern.edu

214-648-8283

References

Briggs LC. Hominid evolution in Northwest Africa and the question of the North African "Neanderthaloids". Am J Phys Anthropol. 1968 Nov;29(3):377-85. doi: 10.1002/ajpa.1330290312. No abstract available.

Reference Type: BACKGROUND

PMID: 5710375 (View on PubMed)

Other Identifiers

R01DK124379

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU-2020-0046

Identifier Type: -

Identifier Source: org_study_id