Bupropion for Fatigue in Kidney Failure

(BRISK Trial)

Overseen By Subrata Debnath, MB.BS, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Bupropion, Antidepressants, MAO inhibitors

Disqualifiers: Eating disorders, Seizure, Depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether bupropion, a medication commonly used for quitting smoking and treating depression, can reduce tiredness in people with end-stage kidney disease on dialysis. Fatigue often affects these patients, making daily life difficult. Participants will take the medication during their regular dialysis sessions for eight weeks. This trial is open to those who have been on dialysis regularly for at least three months and are not currently taking bupropion or experiencing certain health issues like depression or cognitive impairments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to early-stage research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently on bupropion or antidepressants.

Is there any evidence suggesting that bupropion is likely to be safe for humans?

Studies have shown that bupropion is generally well-tolerated. Past research indicates that most patients experienced only minor side effects. Bupropion is already used to treat depression and aid smoking cessation, suggesting its safety. However, in individuals with kidney problems, bupropion remains in the body longer. Therefore, doctors will closely monitor patients' reactions during trials. Overall, early findings suggest that bupropion could be a safe option for managing fatigue, with careful monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for fatigue in kidney failure, which often involve lifestyle changes and medications like erythropoiesis-stimulating agents, bupropion offers a novel approach. Bupropion is unique because it is traditionally used as an antidepressant and smoking cessation aid, but here it's being repurposed to address fatigue by potentially enhancing neurotransmitter activity. Researchers are excited about this treatment because it offers a new way to manage fatigue by using a medication that can be conveniently administered during dialysis sessions, possibly improving the quality of life for those undergoing hemodialysis.

What evidence suggests that bupropion might be an effective treatment for fatigue in kidney failure?

Research has shown that bupropion might help reduce tiredness, especially in people with certain health conditions. In studies with cancer patients, bupropion was well tolerated and showed promise in managing fatigue. Although originally developed to help with depression and smoking cessation, its potential to increase energy levels is under investigation. In this trial, participants in the Hemodialysis Group will receive bupropion to assess its effects on fatigue in individuals with kidney failure. People with kidney problems process bupropion more slowly, so the drug remains in their system longer. This could enhance its effects, but careful monitoring is necessary. Overall, early findings suggest that bupropion could help improve tiredness in those with kidney failure. ^{1 2 5 6 7}

Who Is on the Research Team?

Subrata Debnath, MB.BS, Ph.D.

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

This trial is for end-stage kidney disease patients who experience fatigue while on maintenance hemodialysis. Participants should be currently undergoing routine dialysis and willing to take bupropion tablets during their sessions.

Inclusion Criteria

Blood hemoglobin of ≥10.0 g/dL based on most recent routine laboratory profile

Dialysis adequacy measured with Kt/V of ≥1.2

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Diagnosis of cognitive impairment including dementia

Current participation in another interventional trial

I have had long-term effects after recovering from COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bupropion tablet orally three times a week during routine dialysis procedure for consecutive 8 weeks. Study participants will complete questionnaires and provide biological specimens.

8 weeks

3 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion

Trial Overview The study tests if bupropion, a medication used for depression and to quit smoking, can reduce fatigue in hemodialysis patients. It involves taking the drug three times a week for eight weeks during dialysis, along with completing questionnaires about fatigue and quality of life.

How Is the Trial Designed?

Group I: Hemodialysis Group Experimental Treatment 1 Intervention

Fixed dose bupropion hydrochloride 150 mg extended-release tablets will be administered orally thrice a week during routine dialysis sessions for consecutive 8 weeks.

Bupropion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in Canada as Zyban for:

• Smoking cessation

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Published Research Related to This Trial

This study is a feasibility randomized controlled trial involving 40 adult patients undergoing in-centre haemodialysis, aiming to assess the recruitment and acceptability of a cognitive-behavioral therapy (CBT) intervention for managing fatigue.

The trial will evaluate various self-reported outcomes related to fatigue, sleep quality, and mental health, with data collected at baseline and 3 months post-randomization to determine the potential benefits of the CBT intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioural therapy (CBT) for renal fatigue (BReF): a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients. Picariello, F., Moss-Morris, R., Macdougall, IC., et al.[2018]

In a case series of 15 cancer patients treated with bupropion sustained release (SR) for up to 2 years, 13 patients experienced significant improvement in fatigue symptoms within 2 to 4 weeks.

Most patients tolerated bupropion SR well, with only minor side effects reported, suggesting it may be a safe option for managing fatigue in cancer patients, although further controlled studies are needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion sustained release treatment reduces fatigue in cancer patients. Cullum, JL., Wojciechowski, AE., Pelletier, G., et al.[2017]

Wellbutrin (bupropion) shows potential genotoxic effects in cultured human peripheral blood lymphocytes, indicating it may cause chromosomal damage in vitro.

Despite these findings, the study suggests that the cytogenetic effects of Wellbutrin are unlikely to occur in actual patients, implying a safety margin when used as an antidepressant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Potential In vitro Genotoxic and Cytotoxic Effects of Bupropion Hydrochloride (Wellbutrin) in Human Peripheral Lymphocytes and Human Cortical Neuron. Bhattacharya, SK., Nathawat, LS., Damani, P., et al.[2021]

In a randomized, double-blind, placebo-controlled trial involving 40 cancer patients, bupropion sustained release (SR) significantly improved fatigue levels after four weeks of treatment compared to baseline, indicating its efficacy in managing cancer-related fatigue (CRF).

Bupropion SR was well-tolerated by patients, suggesting it is a safe option for alleviating fatigue in cancer patients, although it did not show significant differences in secondary outcomes like depression or performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Role of Bupropion Sustained Release for Cancer-Related Fatigue: a Double-Blind, Placebo-Controlled Study Ashrafi, F., Mousavi, S., Karimi, M.[2018]

In a study of 274 adults with major depressive disorder, bupropion XL significantly reduced depressive symptoms, particularly in areas of energy, pleasure, and interest, compared to placebo over 8 weeks.

Bupropion XL was well tolerated, with most adverse events being mild or moderate, and showed higher remission and response rates compared to placebo, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study. Jefferson, JW., Rush, AJ., Nelson, JC., et al.[2019]

Approximately 70% of patients with chronic kidney disease (CKD) report experiencing fatigue, which is linked to serious outcomes like hospitalization and increased mortality, highlighting the need for effective management strategies.

Physical activity has shown promise in reducing fatigue in CKD patients, and while erythropoiesis-stimulating agents may help improve fatigue by increasing hemoglobin levels, their use is limited due to potential cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue in CKD: Epidemiology, Pathophysiology, and Treatment. Gregg, LP., Bossola, M., Ostrosky-Frid, M., et al.[2023]

Bupropion (Wellbutrin) was evaluated in four double-blind, placebo-controlled trials involving 360 participants, demonstrating minimal adverse events associated with its use.

The adverse events correlated well with the known pharmacological properties of bupropion, indicating a favorable safety profile for this novel antidepressant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodologic approach to adverse events applied to bupropion clinical trials. Cato, AE., Cook, L., Starbuck, R., et al.[2013]

The Brief Fatigue Inventory (BFI) demonstrated excellent reliability in assessing fatigue in hemodialysis patients, with a high Cronbach's alpha of .92, indicating it is a consistent tool for measuring fatigue levels.

The BFI effectively distinguishes between fatigue severity and interference, and shows a significant correlation with depression levels, suggesting it is a valid measure for understanding fatigue in the context of hemodialysis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychometric Properties of the Brief Fatigue Inventory in Hemodialysis Patients during a Dialysis Day: A Preliminary Report. Debnath, S., Rueda, R., Thomas, N., et al.[2023]

Fatigue is a significant issue for individuals with chronic kidney disease (CKD), affecting 70% to 97% of patients and severely impacting their quality of life.

Most research on fatigue in CKD has concentrated on patients undergoing hemodialysis, leaving a gap in understanding fatigue in those on peritoneal dialysis and transplant patients, highlighting the need for more comprehensive studies in these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue in Patients with Chronic Kidney Disease: Evidence and Measures. Joshwa, B., Campbell, ML.[2018]

In a preliminary study of 21 cancer patients, bupropion sustained release (SR) significantly improved symptoms of fatigue and depression after 4 weeks of treatment, suggesting its potential effectiveness for cancer-related fatigue.

While both depressed and non-depressed patients reported improvements in fatigue and depressive symptoms, only non-depressed patients and their caregivers experienced enhancements in quality of life, indicating that further research is needed to explore these effects comprehensively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label study of the effects of bupropion SR on fatigue, depression and quality of life of mixed-site cancer patients and their partners. Moss, EL., Simpson, JS., Pelletier, G., et al.[2015]

A study involving 25 in-depth interviews with end-stage kidney disease (ESKD) patients revealed that fatigue is significantly influenced by the illness and treatment, with patients interpreting their fatigue in either a catastrophic or normalizing way.

Participants identified three main strategies for managing fatigue: accommodating activities around fatigue, increasing activities to combat it, and practicing self-compassion, highlighting the importance of social support in their experiences and management of fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'It's when you're not doing too much you feel tired': A qualitative exploration of fatigue in end-stage kidney disease. Picariello, F., Moss-Morris, R., Macdougall, IC., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06609343

NCT06609343 | Bupropion for Fatigue in End-stage Kidney ... Primary Objective: To evaluate the feasibility and efficacy of bupropion for the treatment of fatigue in patients with end-stage kidney disease on maintenance ...

2. withpower.com withpower.com/trial/phase-2-kidney-diseases-10-2024-fef26

Bupropion for Fatigue in Kidney Failure (BRISK Trial) Most patients tolerated bupropion SR well, with only minor side effects reported, suggesting it may be a safe option for managing fatigue in cancer patients, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2000634/

Effect of renal impairment on the pharmacokinetics of ... The apparent oral clearance (CL/F) of bupropion was 63% lower (P = 0.001, 95% CI −29%, −96%) in the patients with renal impairment. There were ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/018644s038,020358s045lbl.pdf

WELLBUTRIN - accessdata.fda.gov The elimination of bupropion and/or the major metabolites of bupropion may be 188 reduced by impaired renal function (see PRECAUTIONS: Renal Impairment).

5. journals.lww.com journals.lww.com/americantherapeutics/fulltext/2024/02000/bupropion_overdose_and_acute_renal_failure.9.aspx

Bupropion Overdose and Acute Renal Failure We aim to present a case of acute renal failure because of bupropion overdose, a toxic effect that has not been mentioned in the literature before.

6. trialx.com trialx.com/clinical-trials/listings/302595/bupropion-for-fatigue-in-end-stage-kidney-disease-patients-on-hemodialysis/

Bupropion for Fatigue in End-stage Kidney Disease ... Primary Objective: To evaluate the feasibility and efficacy of bupropion for the treatment of fatigue in patients with end-stage kidney disease ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/534459

Bupropion for Fatigue in End-stage Kidney Disease ... In this study, hemodialysis participants will receive bupropion tablet orally three times a week during routine dialysis procedure for consecutive 8 weeks.