End Stage Renal Disease, Major Depression
Conditions
Keywords
depression, ESRD, hemodialysis
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.
Interventions
DRUGFluoxetine
Antidepressant
DRUGBupropion
Antidepressant
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Fluoxetine: Antidepressant | 0 |
| Bupropion Bupropion sustained release (SR) 150 mg orally twice per week
Bupropion: Antidepressant | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Bupropion | Total | Fluoxetine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | — |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | — |
| Sex: Female, Male Male | 1 Participants | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 1 / 1 |
| other Total, other adverse events | 0 / 0 | 0 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 |
Outcome results
Primary
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.
Time frame: up to 12 weeks
Population: Study was terminated due to inability to recruit. No subjects were recruited for Fluoxetine arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bupropion | Depression Severity | 18 units on a scale |