Bupropion for Depression in ESRD Patients on Hemodialysis

NCT02238977 | Terminated Phase 4 Results

• 2 other identifiers: 203076R21DK097470
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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. 1.Bupropion and fluoxetine will both show efficacy in treating MDD;
2. 2.Bupropion will lead to greater improvement in cognitive dysfunction and fatigue than fluoxetine; and
3. 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

Keywords

depression; ESRD; hemodialysis

Outcome Measures

Primary Outcomes (1)

• Depression Severity

  Depression severity as measured by the 25-item Hamilton Depression Rating Scale. The Hamilton Depression Rating Scale has proven useful for determining the level of depression before, during, and after treatment. It is based on the clinician's interview with the patient/participant and probes symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels and weight loss. The rater enters a number for each symptom construct that ranges from 0 (not present) to 4 (extreme symptoms). The higher the total score the more severe the depression. The scale is scored by summing the total of all items. The maximum possible total score is 66 and the minimum is 0. A score \> 17 is considered compatible with a diagnosis of major depression. A score \< 10 is considered clinical remission. The interview and scoring takes about 15 minutes.

  up to 12 weeks

Study Arms (2)

Fluoxetine

ACTIVE COMPARATOR

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.

Drug: Fluoxetine

Bupropion

EXPERIMENTAL

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

Drug: Bupropion

Interventions

Fluoxetine DRUG

Antidepressant

Also known as: Prozac

Fluoxetine

Bupropion DRUG

Antidepressant

Also known as: Wellbutrin SR

Bupropion

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Kidney Failure, Chronic; Depression

Interventions

Fluoxetine; Bupropion

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Renal Insufficiency, Chronic; 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; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Propiophenones; Ketones

Results Point of Contact

• Title: Pedro Delgado, M.D.
• Organization: University of Arkansas for Medical Sciences

pldelgado@uams.edu

501-526-8100

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2014
• First Posted: September 12, 2014
• Study Start: March 31, 2016
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: July 17, 2018
• Results First Posted: July 17, 2018

Record last verified: 2018-05

Locations

US (1)