Milk Volume Outcomes Following Oral Nicotinamide Riboside Supplementation in Mothers of Extremely Preterm Infants (MOONRISE)

Nicotinamide Riboside and Milk Production in the NICU

Breastfeeding has well-established immunity and developmental benefits for newborns, yet mothers of preterm infants often struggle to provide sufficient breast milk. The investigators hypothesize that supplementing mothers of preterm infants with nicotinamide riboside (NR) during early postpartum will result in increased milk production. NR is a unique precursor to NAD+, which functions in whole-body metabolism, including that which supports the elevated energy demands of lactation. In lactating rats, NR supplementation improved milk quantity and quality, with metabolic benefits for the mother and lasting protective advantages for the offspring. No studies have been conducted to date that explore the short- or long-term use of NR for increasing milk supply in lactating women. This study will follow a small cohort of women and very preterm infants in the NICU throughout two intervention phases-- one in which each mother will randomly receive either NR or a placebo, then the opposite treatment-- to determine the effect of maternal NR supplementation on expressed milk volume and other markers of metabolism.

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm Birth; Inadequate Milk Production
• Intervention / Treatment: Drug: Nicotinamide riboside chloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Bruce German, PhD; Phone Number: (530) 752-1486; Email: jbgerman@ucdavis.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• informed consent for participation of both mother and baby
• infant delivered at ≤28 weeks gestation
• Infant born at the UC Davis Medical Center or transferred to the UC Davis Medical Center NICU within the first 6 days of life.
• Mothers willing to express and measure milk volume

Exclusion Criteria:

• Infant is participating in an intervention trial that could influence growth, development, or feeding tolerance
• Mother has previously undergone breast surgery or has experienced other breast trauma
• Mother is actively using narcotics or amphetamines
• Mothers is receiving cancer treatment
• Mothers is receiving lithium or gold therapies
• Mother plans to use any form of galactagogue (including fenugreek)
• Mother is taking any form of contraceptives or plans to resume use of contraceptive within four weeks of delivery
• Mother is involuntarily confined
• Mother is an adult unable to consent
• Mother resides <50 miles from UC Davis Medical Center
• Anyone deemed unfit for participation by investigator(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NR First; Mothers will receive NR during the first 7 days of intervention, then placebo for the 7 days following washout.	Drug: Nicotinamide riboside chloride; Nicotinamide riboside chloride 250 mg capsules, administered once per day (Day 1-7 or Day 11-17); Other Names: Niagen; Drug: Placebo; Maltodextrin placebo, administered once per day (Day 1-7 or Day 11-17)
Experimental: Placebo First; Mothers will receive placebo during the first 7 days of intervention, then NR for the 7 days following washout.	Drug: Nicotinamide riboside chloride; Nicotinamide riboside chloride 250 mg capsules, administered once per day (Day 1-7 or Day 11-17); Other Names: Niagen; Drug: Placebo; Maltodextrin placebo, administered once per day (Day 1-7 or Day 11-17)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in mean milk volume of expressed milk (mL) between NR and placebo	Measured by 24-hour expressions	Day 2 - Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in mean milk volume of expressed milk (mL) between NR and placebo	Measured by 24-hour expressions	Day 2 - Days 7, 12, 17, and 20
Difference in change in mean milk volume between baseline and each time point (mL) between NR and placebo	Measured by 24-hour expressions	Day 2 - Days 7 and 10; Day 12 - Days 17 and 20
Difference in serum prolactin levels and the difference between NR and placebo	Taken at two time points	Day 2 - Day 10
Concentration of fat, protein, and carbohydrates in expressed milk (g/100 mL)		Day 2 - Day 20
Concentration of metabolite species in maternal urine (μM) between NR and placebo		Day 2 - Day 20
Difference in mean size of milk fat globule (μm) between NR and placebo		Day 10 - Day 20
Average PC/PE ratio of milk fat globule membrane		Day 10 - Day 20
Oligosaccharide content of expressed milk	Measured as relative abundance (%)	Day 2 - Day 20
Infant fecal microbiota	Measured as relative abundance (%)	Day 2 - Day 20
Concentration of BDNF in expressed milk (pg/mL)		Day 2 - Day 20

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maternal weight (lbs.)		Day 2 - Day 20
Infant length (cm)		Day 1 - Day 28
Infant weight (g)		Day 1 - Day 28
Infant head circumference (cm)		Day 1 - Day 28
NICU outcomes	Including morbidity, death, necrotizing enterocolitis, chronic lung disease, sepsis, etc.	Day 1 - Day 28

Collaborators and Investigators

• Sponsor: University of California, Davis

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 1557473

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No