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

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety and effectiveness of melatonin for the prevention of antibiotic associated acute kidney injury in hospitalized patients.

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.

What data supports the effectiveness of the drug melatonin for treating acute kidney injury?

Research shows that melatonin, a hormone made by the pineal gland, has protective effects against acute kidney injury (AKI) due to its antioxidative properties. Studies have found that melatonin can help prevent AKI in patients treated with certain antibiotics and reduce kidney damage in various experimental models. ^{1 2 3 4 5}

Is melatonin safe for use in humans?

Melatonin is generally considered safe for use in humans, with studies showing it is well tolerated even at high doses, such as 20 mg in patients with sepsis. However, some side effects like nightmares, low blood pressure, and sleep disorders have been reported, and its long-term effects and interactions with other systems in the body need further study. ^{3 5 6 7 8}

How does the drug melatonin differ from other treatments for acute kidney injury?

Melatonin is unique in treating acute kidney injury because it acts as a powerful antioxidant, reducing oxidative stress and inflammation, which are key factors in kidney damage. Unlike other treatments, melatonin is a natural hormone produced by the pineal gland, and its protective effects are being explored for both acute and chronic kidney conditions. ^{2 3 5 6 9}

Research Team

Luigi Brunetti, PhD

Principal Investigator

Rutgers, The State University of New Jersey

Eligibility Criteria

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.

I am between 18 and 75 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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]

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]

References

1. Iran pubmed.ncbi.nlm.nih.gov

Could melatonin prevent Vancomycin-induced nephrotoxicity in critically ill patients? A randomized, double-blinded controlled trial. [2023]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Melatonin and renal protection: novel perspectives from animal experiments and human studies (review). [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of melatonin against acute kidney injury: A systematic review and meta-analysis. [2023]

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

Effects of melatonin on suppression of renal scarring in experimental model of pyelonephritis. [2013]

5. England 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. [2023]

6. Singapore pubmed.ncbi.nlm.nih.gov

The role of melatonin treatment in chronic kidney disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Dose assessment of melatonin in sepsis (DAMSEL2) study: Pharmacokinetics of two doses of oral melatonin in patients with sepsis. [2022]

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

Toxicology of melatonin. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Contrast-induced nephropathy: preventive and protective effects of melatonin. [2013]