Bupropion for Fatigue in Kidney Failure

(BRISK Trial)

Overseen By Samin Sharma, MD

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

Trial Summary

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.

What evidence supports the effectiveness of the drug bupropion for reducing fatigue in patients with kidney failure?

Research shows that bupropion can significantly reduce fatigue in cancer patients, suggesting it might also help with fatigue in kidney failure. In studies, patients taking bupropion reported feeling less tired and had improved quality of life. ^{1 2 3 4 5}

Is bupropion generally safe for humans?

Bupropion, used under various names like Wellbutrin and Zyban, has been studied in clinical trials for different conditions, including depression and cancer-related fatigue. These studies generally found that bupropion was well-tolerated with minimal adverse effects, suggesting it is generally safe for human use. ^{1 3 4 5 6}

How is the drug Bupropion unique for treating fatigue in kidney failure?

Bupropion is unique for treating fatigue in kidney failure because it is primarily an antidepressant that works by affecting neurotransmitters (chemical messengers in the brain), which may help alleviate fatigue differently than other treatments like physical activity or erythropoiesis-stimulating agents. Unlike these other treatments, Bupropion's mechanism targets brain chemistry, potentially offering a novel approach to managing fatigue in this population. ^{7 8 9 10 11}

What is the purpose of this trial?

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.

Research Team

Subrata Debnath, MB.BS., Ph.D.

Principal Investigator

The University of Texas Health Science Center at San Antonio

Eligibility Criteria

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

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

Diagnosis of cognitive impairment including dementia

Current participation in another interventional trial

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2015]

2. India 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. [2021]

3. Thailand pubmed.ncbi.nlm.nih.gov

Potential Role of Bupropion Sustained Release for Cancer-Related Fatigue: a Double-Blind, Placebo-Controlled Study [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Bupropion sustained release treatment reduces fatigue in cancer patients. [2017]

5. United States 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. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Methodologic approach to adverse events applied to bupropion clinical trials. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Psychometric Properties of the Brief Fatigue Inventory in Hemodialysis Patients during a Dialysis Day: A Preliminary Report. [2023]

8. England 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. [2023]

9. England 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. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Fatigue in Patients with Chronic Kidney Disease: Evidence and Measures. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Fatigue in CKD: Epidemiology, Pathophysiology, and Treatment. [2023]