Nicotinamide Adenine Dinucleotide Augmentation in Diabetic Kidney Disease: Randomized Trial Study Protocol

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and kidney failure worldwide. Reduced nicotinamide adenine dinucleotide (NAD) levels are mechanistically linked to DKD pathogenesis; and NAD augmentation by administration of its precursor, nicotinamide mononucleotide (NMN), has attenuated albuminuria and kidney injury in preclinical models.

The NAD Augmentation in Diabetic Kidney Disease (NAD in DKD) trial is a phase 2a, randomized, multicenter, double-blind, placebo-controlled, parallel-group study evaluating the efficacy and safety of oral pharmaceutical-grade microcrystalline β-NMN (MIB-626) in adults with DKD. One hundred fifty-six participants aged ≥ 30 years with diabetes, urinary albumin-to-creatinine ratio (UACR) ≥ 100 mg/g, and estimated glomerular filtration rate (eGFR) > 25 ml/min per 1.73 m² were randomized to receive MIB-626 (1000 mg twice daily) or placebo for 24 weeks, followed by 12 weeks of postintervention follow-up. The randomization was stratified for biological sex, age (30-44, 45-65, and ≥ 66 years), and enrolling site. The primary end point was change in UACR from baseline to 24 weeks. Secondary outcomes included serum creatinine, cystatin C, and eGFR, biomarkers of kidney injury and biological age, glycemic control, measures of muscle performance and physical function, and the circulating NAD metabolome.

This phase 2a trial was designed to evaluate the safety and efficacy of NAD augmentation in improving UACR in albuminuric DKD. The results will inform whether NAD augmentation warrants further evaluation in larger trials statistically powered for long-term kidney outcomes. The study is registered at ClinicalTrials.gov (NCT05759468).