Bupropion for Depression in ESRD Patients on Hemodialysis

• Sponsor: University of Arkansas (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02238977
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 1
• Location: 1
• Arms: 2
• Actual Duration (Months): 23
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depression; End Stage Renal Disease	Drug: Fluoxetine; Drug: Bupropion	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bupropion for Depression in ESRD Patients on Hemodialysis
• Actual Study Start Date: Mar 31, 2016
• Actual Primary Completion Date: Mar 1, 2018
• Actual Study Completion Date: Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Fluoxetine; Antidepressant; Other Names: Prozac
Experimental: Bupropion Bupropion sustained release (SR) 150 mg orally twice per week	Drug: Bupropion; Antidepressant; Other Names: Wellbutrin SR

Outcome Measures

Primary Outcome Measures

1. Depression Severity [up to 12 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 10, 2017
• Informed Consent Form - Mar 10, 2017

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT02238977
• Other Study ID Numbers: 203076; R21DK097470
• First Posted: Sep 12, 2014
• Last Update Posted: Jul 17, 2018
• Last Verified: May 1, 2018

• Keywords provided by University of Arkansas: depression; ESRD; hemodialysis
• Additional relevant MeSH terms: Kidney Failure, Chronic; Depression; Depressive Disorder; Bupropion; Fluoxetine

Study Results

Participant Flow

Arm/Group Title	Fluoxetine	Bupropion
Arm/Group Description	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. Fluoxetine: Antidepressant	Bupropion sustained release (SR) 150 mg orally twice per week Bupropion: Antidepressant
Period Title: Overall Study
STARTED	0	1
COMPLETED	0	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fluoxetine	Bupropion	Total
Arm/Group Description	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. Fluoxetine: Antidepressant	Bupropion sustained release (SR) 150 mg orally twice per week Bupropion: Antidepressant	Total of all reporting groups
Overall Participants	0	1	1
Age (Count of Participants)
<=18 years	0 NaN	0 0%
Between 18 and 65 years	0 NaN	0 0%
>=65 years	1 Infinity	1 100%
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 0%
Male	1 Infinity	1 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 NaN	0 0%	0 0%
Asian	0 NaN	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 NaN	0 0%	0 0%
Black or African American	0 NaN	1 100%	1 100%
White	0 NaN	0 0%	0 0%
More than one race	0 NaN	0 0%	0 0%
Unknown or Not Reported	0 NaN	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Depression Severity
Description	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.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

Study was terminated due to inability to recruit. No subjects were recruited for Fluoxetine arm.

Arm/Group Title	Bupropion	Fluoxetine
Arm/Group Description	Bupropion sustained release (SR) 150 mg orally twice per week Bupropion: Antidepressant	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. Fluoxetine: Antidepressant
Measure Participants	1	0
Number [units on a scale]	18

Adverse Events

Time Frame	Up to 12 weeks
Adverse Event Reporting Description	Study was terminated due to inability to recruit. No subjects were recruited for Fluoxetine arm.
Arm/Group Title	Fluoxetine		Bupropion
Arm/Group Description	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. Fluoxetine: Antidepressant		Bupropion sustained release (SR) 150 mg orally twice per week Bupropion: Antidepressant
All Cause Mortality
	Fluoxetine		Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		1/1 (100%)
Serious Adverse Events
	Fluoxetine		Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Fluoxetine		Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.