Bupropion for Depression in ESRD Patients on Hemodialysis

NCT ID: NCT02238977

Last Updated: 2018-07-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-03-01

Brief Summary

The proposed study will evaluate the response and remission rates for major depressive disorder (MDD) in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD) treated with bupropion or fluoxetine for 12 weeks. In addition, the study will document the relative tolerability and safety, and longitudinally contrast the effects of bupropion and fluoxetine on measures of cognitive function, fatigue, inflammation, and tryptophan (TRP) and TRP catabolites in blood. It is hypothesized that both drugs will significantly reduce MDD symptoms from baseline, and be tolerable and safe, but bupropion will be associated with greater reduction in pro-inflammatory cytokines, cognitive impairment, and fatigue compared with fluoxetine.

The Specific Aims of this study are:

Aim 1: Determine the efficacy of bupropion and fluoxetine in treatment of MDD in ESRD/HD patients.

Aim 2: Determine whether longitudinal change in MDD symptoms, cognitive dysfunction, and fatigue differ between bupropion and fluoxetine.

Aim 3: Determine whether longitudinal change in MDD symptoms, cognitive dysfunction, and fatigue correlate with change in inflammation, measures of TRP availability to brain, or neurotoxic TRP metabolites.

Hypotheses:

1. Bupropion and fluoxetine will both show efficacy in treating MDD;

2. Bupropion will lead to greater improvement in cognitive dysfunction and fatigue than fluoxetine; and

3. Change in cognition and fatigue over time will correlate with change in c-reactive protein (CRP) and quinolinic acid and change in overall depression score will correlate with measures of TRP availability.

Conditions

Major Depression; End Stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fluoxetine

Fluoxetine up to 20 mg orally daily for 12 weeks. Flexible dosing between a minimum of 10 mg daily and 20 mg daily as tolerated.

Group Type: ACTIVE_COMPARATOR

Fluoxetine

Intervention Type: DRUG

Antidepressant

Bupropion

Bupropion sustained release (SR) 150 mg orally twice per week

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

Antidepressant

Interventions

Fluoxetine

Antidepressant

Intervention Type: DRUG

Bupropion

Antidepressant

Intervention Type: DRUG

Other Intervention Names

Prozac; Wellbutrin SR

Eligibility Criteria

Inclusion Criteria

• age 30-70 yrs;
• have patent and non-infected arteriovenous fistula or graft;
• are receiving maintenance HD 3 times per week lasting for 3-4 hours;
• serum albumin of ≥ 3.2 g/dl, serum phosphate of <6.5 mg/dl, and serum hemoglobin of ≥9 mg/dl in consecutive two blood tests as per the National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI) guidelines [subjects failing screening due to blood test will be allowed to be re-screened in 30 days];
• receiving stable or maintenance dose of iron or erythropoietin-stimulating agents, statins, angiotension receptor blockers and/or angiotension converting enzyme inhibitors, phosphate binders, vitamin D receptor analogs as these agents may influence cytokines proposed in the study;
• meet the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for MDD;
• have a Ham-D score > 17

Exclusion Criteria

• meet DSM-IV criteria for Bipolar Disorder or other psychotic disorder in the month prior to screening;
• are taking antidepressants, anti-anxiety medications, or hypnotics (including Zyban for smoking cessation);
• having failed to respond to or tolerate bupropion or fluoxetine in the past
• allergic to fluoxetine or bupropion
• known history of HIV/AIDS; No testing will be conducted for screening purposes
• known history of alcohol or drug abuse or dependence within the month prior to screening based on clinical records;
• history of myocardial infarction or heart failure within one month of screening or a history of seizures or stroke at any point;
• history of chronic liver disease and diagnosis of hepatic encephalopathy based on clinical records;
• currently diagnosed with cancer or receiving any cancer treatment;
• history of any infection within the last 2 weeks ;
• currently taking any antibiotics, anti-inflammatory, and immune-modulator agents;
• recorded noncompliance with dialysis schedules; and
• currently participating in clinical or behavioral intervention studies.
• recorded noncompliance with dialysis schedules; and
• currently participating in clinical or behavioral intervention studies

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Arkansas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21DK097470

Identifier Type: NIH

Identifier Source: secondary_id

View Link

203076

Identifier Type: -

Identifier Source: org_study_id