Melatonin for Prevention of Kidney Injury

Melatonin for the Prevention of Antibiotic Associated Acute Kidney Injury

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

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Adverse Drug Event
• Intervention / Treatment: Drug: Melatonin; Other: Placebo Capsule

Detailed Description

Consenting subjects meeting inclusion and exclusion will be randomized to receive melatonin 5 mg daily or a matching placebo. Study subjects will be followed for the duration of hospitalization or discontinuation of broad spectrum antibiotics (vancomycin plus piperacillin/tazobactam). The primary outcome and secondary outcomes will be evaluated by the study team.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Luigi Brunetti, PhD; Phone Number: 908-595-2645; Email: luigi.brunetti@rutgers.edu

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Robert Wood Johnson University Hospital
      • Contact: Pinki Bhatt, MD; Phone Number: 732-235-2898; Email: pb518@rwjms.rutgers.edu
    • Somerville, New Jersey, United States, 08876
      • Recruiting
      • Robert Wood Johnson University Hospital Somerset
      • Principal Investigator: Luigi Brunetti, PhD
      • Contact: Luigi Brunetti, PhD; Phone Number: 2016385868; Email: brunetti@pharmacy.rutgers.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Aged 18 to 75 years
• Currently prescribed vancomycin with the presumption that therapy will be continued for at least 3 days based on a review of subject status. Because of the critical nature of starting empiric broad-spectrum antibiotics, we will allow one dose of the antibiotic combination before consent and enrollment. This strategy is necessary for the ethical conduct of the study.

Exclusion criteria:

• Estimated creatinine clearance < 30 mL/min
• Liver impairment (liver enzymes > 3 times upper limit)
• Any history of allergy or contraindication to melatonin
• Pregnancy or breastfeeding
• Autoimmune disease
• Requiring vasopressors
• Requiring mechanical ventilation
• History of acute kidney injury in the past 30 days
• Inability to take oral medications
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin Arm; Melatonin 5 mg capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.	Drug: Melatonin; Melatonin 5 mg capsule by mouth at bedtime
Placebo Comparator: Placebo Arm; Placebo capsule by mouth at bedtime for the duration of hospitalization or discontinuation of broad spectrum antibiotics, whichever comes first.	Other: Placebo Capsule; Placebo capsule by mouth at bedtime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	Acute kidney injury will be defined as an increase in sCr from baseline of >/= 0.3 mg/dL or a >/= 50% increase from baseline.	From date of randomization until the date of first documented acute kidney injury or date of antibiotic discontinuation, whichever came first, assessed up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Melatonin plasma trough concentration	Evaluate the steady state plasma trough concentration of melatonin	Days 3, 5, and 7
Piperacillin/tazobactam plasma trough concentration	Evaluate the steady state plasma trough concentration of piperacillin/tazobactam	Days 3, 5, and 7
Vancomycin plasma Area Under the Curve (AUC)	Evaluate the steady state plasma AUC of vancomycin	Days 3, 5, and 7
Association between Kidney Injury Molecule-1 (KIM-1) and serum creatinine	Measure KIM-1 in plasma and urine and evaluate discordance between serum creatinine.	Days 3, 5, and 7
Mitochondrial stress assessment via extracellular flux analysis to measure oxygen consumption rate of cells	Evaluate mitochondrial stress in peripheral blood mononuclear cells from a subset of subjects in each group. In addition, mitochondrial stress will be evaluated on day 3 in a subset in the melatonin group.	Days 1 and 3
Urine mitochondrial DNA copy number	Measure mitochondrial DNA (mtDNA) in urine samples using polymerase chain reaction (PCR).	Days 1, 3, 5, and 7
Fold-change in NRF-2 gene expression in peripheral blood mononuclear cells	Measure gene expression level at baseline and then on day 5 (or last day of study if earlier) using polymerase chain reaction (PCR) and compare the fold-change from baseline between groups.	Days 1 and 5
Number of subjects with NRF2 DNA single nucleotide polymorphisms	Determination of the number of individuals with NRF2 DNA single nucleotide polymorphisms in the study population and compare the incidence of primary outcome in those with and without polymorphisms.	Day 1
Number of subjects with KEAP1 DNA single nucleotide polymorphisms	Determination of the number of individuals with KEAP1 DNA single nucleotide polymorphisms in the study population and compare the incidence of primary outcome in those with and without polymorphisms.	Day 1

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Investigators: Principal Investigator: Luigi Brunetti, PhD, Rutgers, The State University of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: September 13, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chemically-Induced Disorders; Renal Insufficiency; Acute Kidney Injury; Drug-Related Side Effects and Adverse Reactions; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Tryptamines; Melatonin
• Other Study ID Numbers: Pro2021001502

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No