An adequate supply of a mother’s own milk is critical to optimise health outcomes for at-risk hospitalised infants. Mothers of infants admitted to the neonatal intensive care unit (NICU) are disproportionately affected by insufficient milk production. In current U.S. practice, metoclopramide is the only drug available for off-label use as a galactagogue.
Preclinical evidence in a murine model indicates that nicotinamide riboside (NR), a direct precursor to NAD+, can increase high-quality milk production and improve cognitive and physical development of offspring. Human testing of NR has been limited, and prior studies have not examined its effects in lactating individuals. The MOONRISE pilot feasibility trial was designed to assess whether supplementing NICU mothers with NR is feasible and to collect preliminary biological and clinical data to inform future trials.
MOONRISE is a double-blind, randomised, placebo-controlled pilot feasibility trial. The trial targets mothers whose infants are anticipated to be hospitalised in the NICU for at least 4 weeks. The study will enrol mother–infant pairs for a short-term intervention and biospecimen collection protocol.
The protocol plans to enrol 40 mother–infant pairs with the expectation that approximately 30 pairs will complete the study (anticipated n=15 per study arm). The primary feasibility metric is the ability to enrol at least 50% of eligible mothers. Secondary feasibility measures include participant compliance with the intervention, adherence to study procedures, and rates of withdrawal from the protocol.
The intervention period for maternal NR supplementation or matched placebo is 19 days, which includes an enrollment day. During this window, maternal milk, urine and blood samples will be collected according to the protocol to evaluate biochemical and compositional outcomes.
The primary endpoint of this pilot is a feasibility outcome: enrolling ≥50% of eligible mothers. Secondary endpoints cover feasibility-related metrics (compliance, adherence, withdrawal) and biologic and clinical measures comparing the NR and placebo groups. Planned secondary comparisons include:
Optional secondary clinical laboratory endpoints reported in the protocol summary include differences in serum prolactin, liver function tests, the maternal plasma lipidome, serum metabolites, serum cellular communication network factor 3 (CCN3) concentrations, and serum levels of NAD+-related precursors and intermediates.
The protocol lists additional optional assays and metabolomic profiling that may provide mechanistic insight if performed. Exploratory outcomes include changes in maternal weight and infant developmental and NICU clinical outcomes. As a pilot feasibility trial, MOONRISE is intended to gather preliminary effect estimates and feasibility metrics rather than provide definitive efficacy conclusions.
Safety endpoints include the frequency of adverse events observed during the intervention and follow-up window. The source summary indicates that adverse event frequency will be captured and reported as part of trial outcomes. Specific safety monitoring procedures and stopping rules were not detailed in the provided summary.
The study protocol received Institutional Review Board approval at the University of California Davis Medical Center. The protocol version date is 1 June 2026 and the IRB approval number is 1557473. Investigators will communicate trial results to participants, healthcare professionals and the public through peer-reviewed publications and presentations at scientific conferences.
Deidentified participant-level data will be made available to qualified researchers upon request after publication. Access to deidentified data will require study team and IRB approval and a data use agreement; approved requests will be granted access within 12 months, per the protocol summary.
The trial is registered on ClinicalTrials.gov under identifier NCT04614714. Trial results will also be reported on ClinicalTrials.gov and made available through PubMed Central in accordance with regulatory requirements. Investigators plan to disseminate findings through scientific conferences and peer-reviewed journals.
This report describes a pilot feasibility protocol and therefore is not designed or powered to demonstrate definitive efficacy of NR for increasing milk production. Details such as exact NR dosing regimens, specific laboratory assay methods, and full statistical analysis plans were not reported in the provided summary and would be required for evaluation of reproducibility and planning of a larger efficacy trial.
MOONRISE is a randomized, double-blind, placebo-controlled pilot trial testing nicotinamide riboside supplementation versus placebo in mothers with infants expected to remain in the NICU for at least 4 weeks. The study focuses primarily on feasibility of enrolment and adherence, while collecting preliminary data on milk volume, milk composition, metabolomic measures and selected maternal and infant outcomes to inform future definitive studies.