Melatonin for Acute Kidney Injury

Recruiting at 1 trial location

Overseen By Luigi Brunetti, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Rutgers, The State University of New Jersey

Must be taking: Vancomycin

Disqualifiers: Kidney injury, Liver impairment, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether melatonin can safely and effectively prevent kidney damage caused by antibiotics in hospitalized patients. Participants will receive either a melatonin capsule or a placebo (a pill with no active ingredients) each night during their hospital stay. The trial seeks patients aged 18-75 who are taking the antibiotic vancomycin for at least three days. Hospitalized individuals on vancomycin may qualify for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to important research that could lead to a new treatment option.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it requires that you continue taking vancomycin for at least 3 days.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that melatonin is generally safe for use. Studies have examined its role in preventing sudden kidney problems, known as acute kidney injury (AKI), and found it safe. Some studies even suggest that melatonin can enhance kidney function by improving the estimated glomerular filtration rate, a measure of kidney performance.

While melatonin did not prevent AKI in every case, no major reports of serious side effects or problems have emerged. Since this trial is in a later stage, melatonin has already passed earlier safety tests. This makes melatonin a promising option for those considering participation in a clinical trial focused on preventing AKI. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute kidney injury?

Melatonin is unique because it offers a novel approach to treating acute kidney injury, which typically relies on supportive care like dialysis or managing the underlying cause. Unlike traditional treatments, melatonin is a hormone known for its antioxidant and anti-inflammatory properties, which may help protect the kidneys from damage. Researchers are excited about melatonin's potential to minimize kidney damage quickly and safely, possibly reducing the need for more invasive interventions.

What evidence suggests that melatonin might be an effective treatment for acute kidney injury?

Research has shown that melatonin might protect against sudden kidney problems, known as acute kidney injury (AKI). Some studies suggest that melatonin can improve kidney function, while other research does not find a clear benefit in reducing AKI. This trial will compare melatonin with a placebo to better understand its effectiveness for this condition. Considering both the potential benefits and the uncertainty highlighted in current research is important. ^{1 2 5 6 7}

Who Is on the Research Team?

Luigi Brunetti, PhD

Principal Investigator

Rutgers, The State University of New Jersey

Are You a Good Fit for This Trial?

This trial is for hospitalized patients aged 18-65 who are taking antibiotics vancomycin and piperacillin/tazobactam, expected to continue for at least 3 days. It's not for those with severe kidney issues, pregnant or breastfeeding women, people unable to take oral meds, unstable illnesses, recent acute kidney injury, significant liver problems, melatonin allergies, autoimmune diseases or those on strong heart medications or ventilators.

Inclusion Criteria

I am taking vancomycin and expected to continue for at least 3 days.

Exclusion Criteria

Any history of allergy or contraindication to melatonin

Autoimmune disease

Clinical evidence of significant unstable or uncontrolled illness which, in the opinion of the research team, could confound the results of the study or put the patient at undue risk.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive melatonin 5 mg or placebo daily for the duration of hospitalization or until discontinuation of broad spectrum antibiotics

Up to 28 days

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin
• Placebo Capsule

Trial Overview The study tests if melatonin can prevent kidney damage in patients receiving certain antibiotics. Participants will either receive a placebo capsule or melatonin alongside their antibiotic treatment to compare the safety and effectiveness of melatonin against no active intervention.

How Is the Trial Designed?

Group I: Melatonin Arm Experimental Treatment 1 Intervention

Melatonin 5 mg capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.

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

Approved in European Union as Circadin for:

• Insomnia in adults aged 55 and over
• Sleep disorders in children with autism spectrum disorder

Approved in European Union as Slenyto for:

• Insomnia in children and adolescents aged 2-18 with autism spectrum disorder

Approved in United States as Melatonin for:

• Sleep disorders in children with autism spectrum disorder
• Insomnia in adults

Who Is Running the Clinical Trial?

Rutgers, The State University of New Jersey

Lead Sponsor

Trials

471

Recruited

81,700+

Published Research Related to This Trial

Melatonin may improve glomerular filtration rate (GFR), but it does not significantly reduce the incidence of acute kidney injury (AKI) compared to control groups in randomized controlled trials, based on a meta-analysis of five studies.

The findings suggest that while melatonin has potential benefits for kidney function, there is currently insufficient evidence to support its use as a preventive treatment for AKI, highlighting the need for more robust clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of melatonin against acute kidney injury: A systematic review and meta-analysis. Yang, J., Gan, Y., Feng, X., et al.[2023]

Melatonin has shown protective effects in chronic kidney disease (CKD) by reducing oxidative stress, inflammation, and cell death in various animal models, which could help slow disease progression and limit the need for dialysis or transplantation.

In humans, melatonin improves sleep disturbances in hemodialyzed patients and enhances iron metabolism, suggesting its potential as a safe and effective treatment for CKD-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin and renal protection: novel perspectives from animal experiments and human studies (review). Hrenak, J., Paulis, L., Repova, K., et al.[2019]

Melatonin treatment may help improve sleep disturbances in patients with Chronic Kidney Disease (CKD), particularly those undergoing hemodialysis, by addressing melatonin deficiency and circadian rhythm disorders.

In addition to its effects on sleep, melatonin may also benefit CKD patients by helping to regulate blood pressure and providing protection against oxidative stress and inflammation in renal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of melatonin treatment in chronic kidney disease. Russcher, M., Koch, B., Nagtegaal, E., et al.[2022]

In a rat model of pyelonephritis, melatonin combined with antibiotics significantly reduced harmful malondialdehyde levels and neutrophil infiltration, indicating its protective effects against renal damage.

The combination treatment of melatonin and antibiotics effectively prevented renal scarring, showing similar outcomes to the control group, while neither treatment alone was as effective in reducing scarring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of melatonin on suppression of renal scarring in experimental model of pyelonephritis. Imamoğlu, M., Cay, A., Cobanoglu, U., et al.[2013]

Melatonin, while available over the counter in the U.S. and considered safe at normal doses, lacks comprehensive toxicological data, which is necessary for regulatory approval and safety assessment.

Potential side effects of melatonin include nightmares, hypotension, and sleep disorders, and its long-term use could disrupt circadian rhythms and lead to receptor desensitization, highlighting the need for careful evaluation of its pharmacodynamics and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicology of melatonin. Guardiola-Lemaître, B.[2017]

In a study involving 24 male rats, melatonin showed a significant protective effect against contrast-induced nephropathy (CIN) when administered both before and after the contrast agent infusion, improving renal function markers compared to untreated rats.

Rats that were only pre-treated with melatonin did not experience the same protective benefits, indicating that timing of melatonin administration is crucial for its effectiveness in preventing CIN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-induced nephropathy: preventive and protective effects of melatonin. Gazi, S., Altun, A., Erdogan, O.[2013]

In a pilot study involving 90 ICU patients receiving vancomycin, oral melatonin (3 mg twice daily for 7 days) significantly reduced the incidence of acute kidney injury (AKI) compared to a placebo, as indicated by lower levels of plasma neutrophil gelatinase-associated lipocalin (NGAL).

Despite no significant differences in baseline kidney function markers between the melatonin and placebo groups, the findings suggest that melatonin may offer nephroprotective benefits during vancomycin therapy, warranting further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could melatonin prevent Vancomycin-induced nephrotoxicity in critically ill patients? A randomized, double-blinded controlled trial. Abbasi, S., Bigharaz, E., Farsaei, S., et al.[2023]

In an open-label trial involving critically ill patients with sepsis, high-dose oral melatonin (20 or 50 mg) was well tolerated with no adverse events reported, indicating its safety for this patient population.

Pharmacokinetic analysis revealed that the 20 mg dose of melatonin is appropriate, as higher doses (50 mg) resulted in extremely high melatonin levels but did not increase the levels of its major metabolite, suggesting a saturation effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose assessment of melatonin in sepsis (DAMSEL2) study: Pharmacokinetics of two doses of oral melatonin in patients with sepsis. Galley, HF., Allen, L., Colin, PJ., et al.[2022]

In a randomized clinical trial involving 88 patients receiving polymyxin B, melatonin did not significantly reduce the incidence of acute kidney injury (AKI) compared to placebo, with similar rates of AKI observed in both groups.

The study found that the incidence of AKI was 81.9 per 1000 patient-days in the melatonin group and 77.4 per 1000 patient-days in the placebo group, indicating no beneficial effect of melatonin on kidney safety during polymyxin B treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial. Rigatto, MH., Bergo, P., Baldissera, G., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38010077/

PROTECTIVE ROLE OF MELATONIN FOR ACUTE ... Melatonin can increase the estimated glomerular filtration rate and effectively inhibit the occurrence of AKI.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37279642/

Effects of melatonin against acute kidney injury In our study, the present results do not support a direct effect of melatonin use on the reduction of AKI. More well-designed clinical ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05084196

NCT05084196 | Melatonin for Prevention of Kidney Injury This study will evaluate the safety and effectiveness of melatonin for the prevention of antibiotic associated acute kidney injury in hospitalized patients.

4. clinicalmicrobiologyandinfection.org clinicalmicrobiologyandinfection.org/article/S1198-743X(22)00641-3/fulltext

Melatonin for prevention of acute kidney injury in patients ... Outcomes. The primary outcome was the incidence rate of AKI according to the risk of renal failure, injury to the kidney, loss of kidney function and end ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576923006951

Effects of melatonin against acute kidney injury Conclusions. In our study, the present results do not support a direct effect of melatonin use on the reduction of AKI. More well-designed clinical studies ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10047594/

Melatonin Treatment in Kidney Diseases - PMC This means that the supplementation of melatonin can be helpful in almost every type of kidney injury because inflammation, apoptosis, and oxidative stress ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1198743X22006413

Melatonin for prevention of acute kidney injury in patients ... Melatonin initiated in the first 48 hours of therapy did not reduce the incidence of AKI in patients treated with polymyxin B.