Melatonin for Prevention of Kidney Injury

Acute Kidney Injury Clinical Trial

Official title:

Melatonin for the Prevention of Antibiotic Associated Acute Kidney Injury

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05084196
• Other study ID #: Pro2021001502
• Status: Recruiting
• Phase: Phase 3
• Start date: June 5, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: December 2023
• Source: Rutgers, The State University of New Jersey
• Contact: Luigi Brunetti, PhD
• Phone: 908-595-2645
• Email: luigi.brunetti[@]rutgers.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2026
• Est. primary completion date: June 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Adverse Drug Event
• Drug-Related Side Effects and Adverse Reactions
• Wounds and Injuries

Intervention

Drug:
• Melatonin
Melatonin 5 mg capsule by mouth at bedtime

Other:
• Placebo Capsule
Placebo capsule by mouth at bedtime

Locations

Country	Name	City	State
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Melatonin plasma trough concentration	Evaluate the steady state plasma trough concentration of melatonin	Days 3, 5, and 7
Other	Piperacillin/tazobactam plasma trough concentration	Evaluate the steady state plasma trough concentration of piperacillin/tazobactam	Days 3, 5, and 7
Other	Vancomycin plasma Area Under the Curve (AUC)	Evaluate the steady state plasma AUC of vancomycin	Days 3, 5, and 7
Other	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
Other	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
Other	Urine mitochondrial DNA copy number	Measure mitochondrial DNA (mtDNA) in urine samples using polymerase chain reaction (PCR).	Days 1, 3, 5, and 7
Other	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
Other	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
Other	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
Primary	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