Fatigue is the most common symptom reported by end-stage kidney disease patients on maintenance hemodialysis. Unfortunately, there currently is no medical management for this overwhelming feeling of tiredness. As a result, patients continue to suffer with poor quality of life and impaired daily activities. The purpose of this pilot trial is to find out if bupropion (a medicine commonly prescribed for stopping smoking, seasonal mood disorder, and depression) may help lessen fatigue in hemodialysis patients.

In this study, hemodialysis participants will receive bupropion tablet orally three times a week during routine dialysis procedure for consecutive 8 weeks. Study participants will complete a battery of questionnaires to self-report fatigue, cognition, and quality of life. The study team will collect biological specimens. All these procedures will be performed at the dialysis clinic during routine dialysis procedure.

While taking part in this study, participants will be asked to complete study procedures with the researchers or study staff three times a week during routine dialysis visits. Collections of blood, urine (if available) and stool will be collected at different time points over the 8-week intervention. Blood will be analyzed for markers of inflammation, amino acids, and for safety labs as needed. Blood will also be tested for pharmacokinetics of bupropion.

Primary Objective: To evaluate the feasibility and efficacy of bupropion for the treatment of fatigue in patients with end-stage kidney disease on maintenance hemodialysis.

Secondary Objective: To evaluate the effect of bupropion in reducing inflammatory markers in hemodialysis patients with fatigue.

Exploratory Objective: To examine whether bupropion improves cognitive function.

Inclusion Criteria:

1. Male and female ESKD patients between aged 25-74 yrs on maintenance in-center hemodialysis procedure 3 times/week for ≥3 months with an arteriovenous fistula or graft.
2. Blood hemoglobin of ≥10.0 g/dL based on most recent routine laboratory profile.
3. Dialysis adequacy measured with Kt/V of ≥1.2
4. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Currently on bupropion or hypersensitivity/ intolerance to bupropion by history and monoamine oxidase inhibitors.
2. Diagnosis or history of eating disorders (bulimia or anorexia nervosa) and seizure.
3. Pregnant, lactating, childbearing women
4. History of post-acute COVID-19 syndrome
5. Diagnosis of depression and/or on antidepressants and bipolar affective disorder
6. Patient Health Questionnaire (PHQ)-9 score of ≥10
7. Diagnosis of cognitive impairment including dementia
8. Current participation in another interventional trial
9. Scheduled for kidney transplantation in next 6 months
10. Life expectancy <6 months as judged by the attending nephrologist/primary care physician.
11. Current or history of substance abuse or dependency.

Any manuscript, abstract or other publication or presentation of results or information arising in connection with the trial (including any ancillary trial involving trial participants) must use deidentified data.

At study completion at the time of publication in a peer review journal