Combination of Novel Therapies for CKD Comorbid Depression

NCT04422652 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STU-2020-0046R01DK124379
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)

  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.

  Assessed at baseline and weeks 4, 6, 8, 12, and 16

Secondary Outcomes (9)

• Serious adverse events

  Assessed at weeks 4, 6, 8, 12, and 16.

• Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)

  Assessed at baseline and weeks 4, 6, and 8.

• Serious adverse events with monotherapy

  Assessed at weeks 4, 6, and 8.

• Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C)

  Assessed at weeks 8, 12, and 16.

• High sensitivity C-reactive protein

  Assessed at baseline and week 8

Study Arms (3)

Strategy 1

ACTIVE COMPARATOR

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.

Behavioral: Behavioral activation therapy; Drug: Placebo

Strategy 2

ACTIVE COMPARATOR

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.

Drug: Bupropion; Other: Clinical Management

Control

PLACEBO COMPARATOR

Control: Clinical management attention control plus placebo for 16 weeks

Drug: Placebo; Other: Clinical Management

Interventions

Bupropion DRUG

Bupropion is an anti-depressant medication.

Also known as: Wellbutrin

Strategy 2

Behavioral activation therapy BEHAVIORAL

Brief behavioral activation treatments administered via video tele-conferencing.

Strategy 1

Placebo DRUG

Double-blind placebo.

Control; Strategy 1

Clinical Management OTHER

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

Control; Strategy 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• Stony Brook University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (4)

Stony Brook University Medical Center

Stony Brook, New York, 11794-8430, United States

NOT YET RECRUITING

Parkland Health and Hospital System

Dallas, Texas, 75235, United States

RECRUITING

UT Southwestern and Affiliates

Dallas, Texas, 75390, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 5710375 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Depressive Disorder, Major; Kidney Failure, Chronic

Interventions

Bupropion

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Study Officials

• Susan Hedayati, MD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meredith McAdams, MD

CONTACT

214-645-5418; Meredith.McAdams@UTSouthwestern.edu

Ana Arroyo

CONTACT

214-648-8283; ana.arroyo@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR, IM-Nephrology

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 9, 2020
• Study Start: September 24, 2020
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)