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

Nicotinamide Riboside and Milk Production in the NICU

This study aims to evaluate the feasibility and effects of nicotinamide riboside (NR) supplementation in lactating mothers of infants expected to be hospitalized in the neonatal intensive care unit (NICU) for at least four weeks.

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm Birth; Inadequate Milk Production
• Intervention / Treatment: Other: Nicotinamide Riboside (NR); Other: Placebo

Detailed Description

An adequate supply of a mother's own milk plays a critical role in optimizing health outcomes for at-risk infants, such as preterm and medically or surgically complex term infants. Despite this, insufficient milk production disproportionately affects the mothers of these infants. In the United States, metoclopramide is the only drug approved by the FDA for off-label use as a galactagogue. Nicotinamide riboside (NR), a niacin precursor, has been shown in a murine model to support lean body composition in lactating dams while augmenting high-quality milk production and enhancing cognitive and physical development of pups. Human testing with NR has been limited to long-term safety and bioavailability measures. This study aims to assess the feasibility of NR supplementation in mothers whose infants are admitted to the NICU for at least 4 weeks.

To address this gap, this study will enroll a small cohort of mothers with infants, either born preterm (<32 weeks of gestation) or term infants with complex medical or surgical conditions, admitted to the NICU for at least four weeks.

This double-blinded, randomized, placebo-controlled pilot feasibility trial aims to investigate NR supplementation in mothers of infants who are hospitalized in the NICU for at least 4 weeks. The intervention period with maternal nicotinamide riboside supplementation/placebo and maternal milk, urine, and blood sampling will be 19 days, including an enrollment day.

We aim to establish the feasibility of conducting a supplementation study in mothers of hospitalized infants, with enrollment feasibility defined as enrolling ≥ 50% eligible mothers.

Secondary objectives include assessing feasibility metrics (supplement compliance, milk sample collection adherence, and withdrawal rates); protocol adherence; and the impact of nicotinamide riboside supplementation on milk volume, milk composition (including macro- and micronutrient composition, glycans, metabolites, lipidomics, and CCN3), and urinary metabolites. Remnant infant blood samples will be used to examine the relationship between infant feeding practices and neonatal insulin, glucose, and amino acid concentrations.

An optional component of the study is the collection of maternal blood to assess the impact of NR supplementation on the concentration of serum prolactin, AST, ALT, metabolites, and CCN3; plasma lipidomics; and whole blood concentration of NAD+ related precursors.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Nicole Cacho, DO; Phone Number: 916-619-6081; Email: ntcacho@ucdavis.edu
• Study Contact Backup: Name: Kara Kuhn Riordon, MD; Phone Number: 916-619-6081; Email: kmkuhn@ucdavis.edu

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria are required to be met before or at enrollment:

Mothers who are 18 years or older.

Infants delivered at 24-32 weeks OR infants (any GA) that researchers anticipate will be hospitalized in the NICU for at least 4 weeks, including, but not limited to, infants with a diagnosis of gastroschisis, a cardiac defect, intestinal atresia, etc.

Infants born at the UC Davis Medical Center or transferred to the UC Davis Medical Center NICU within the first 7 days of life.

Mothers who attempted initial milk expression within 12 hours of delivery.

Mothers who attempted milk expression at least 6 times every 24 hours from 72 hours after delivery to the Enrollment Visit.

Mothers who have delivered at least 96 hours (4 days) prior to the Enrollment Visit.

Mothers who have experienced a level "3" on the OMPQ before starting the collection of their first 24-hour pooled milk sample (study days 0-3).

Mothers who plan to feed their infants breast milk for at least 3 months.

Mothers who were pregnant with one infant.

Mothers willing to refrain from tandem feeding (directly breastfeeding) another child during the study period.

Mothers willing to refrain from enrolling themselves in another intervention trial during the study period.

Mothers willing to express, weigh, record, and collect 24-hour pooled milk

Mothers willing to remove nipple piercings during the study period.

Mothers willing to refrain from using pseudoephedrine (often found in Sudafed, Theraflu, Claritin-D, etc.) during the study period.

Mothers willing to express milk 6 times or more every 24 hours, including at least once during the night, and with no more than 5 hours between milk expression sessions, during the study period.

Mothers willing to refrain from consuming non-study supplements that contain nicotinamide-riboside (or similar derivatives, including NMN) during the study period.

Mothers willing to refrain from consuming galactagogues during the study period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide Riboside (NR); Mothers receive daily oral nicotinamide riboside chloride 250 mg supplementation per day for 14 days (+ 2 days extra capsule for loss or extending sample collection), from study Day 4 + 1 day [D4-5] to study Day 17 + 2 days [D17-19].	Other: Nicotinamide Riboside (NR); Mothers receive daily oral nicotinamide riboside chloride 250 mg supplementation per day for 14 days (+ 2 days extra capsule for loss or extending sample collection), from study Day 4 + 1 day [D4-5] to study Day 17 + 2 days [D17-19].
Placebo Comparator: Placebo; Mothers receive a daily oral placebo, microcrystalline cellulose 250 mg per day matched in appearance and schedule to the nicotinamide riboside supplement for 14 days (+ 2 days extra capsule for loss or extending sample collection), from study Day 4 + 1 day [D4-5] to study Day 17 + 2 days [D17-19].	Other: Placebo; Mothers receive a daily oral placebo, microcrystalline cellulose 250 mg per day matched in appearance and schedule to the nicotinamide riboside supplement for 14 days (+ 2 days extra capsule for loss or extending sample collection), from study Day 4 + 1 day [D4-5] to study Day 17 + 2 days [D17-19].

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of enrollment in a double-blind placebo-controlled supplementation trial in mothers of infants who are hospitalized.	Proportion of eligible mothers who consent to enrollment in the study.	Within 4 days post-delivery of the infant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in mean milk volume of expressed milk (mL) between NR and placebo	Comparison of total 24-hour expressed breast milk volume (in milliliters) between mothers receiving nicotinamide riboside and those receiving placebo.	Volumes will be measured on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Difference in human milk micronutrient concentrations between NR and placebo over time.	Comparison of human milk micronutrient concentrations (Micrograms per liter (µg/L) or milligrams per liter (mg/L), depending on the element) between mothers receiving nicotinamide riboside and those receiving a placebo. Milk samples collected on study days will be analyzed using inductively coupled plasma mass spectrometry (ICP-MS) in a certified analytical laboratory.	Milk samples will be collected on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Difference in amount and diversity of metabolites, including NAD+-related precursors and intermediates in milk between NR and placebo over time.	NMR metabolomics will be used to compare the amount and diversity of metabolites, including NAD⁺-related precursors and intermediates (e.g., nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, NAD⁺) between the NR group and the placebo from the milk samples collected on various study days.	Milk samples will be collected on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Difference in human milk glycans (HMOs, glycoproteins, glycolipids) between NR and placebo over time.	Comparison of human milk oligosaccharides (HMOs), glycoproteins, and glycolipids in milk samples collected on study days between NR and placebo groups using Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics.	Milk samples will be collected on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Difference in milk lipidomics in milk between NR and placebo over time.	The difference in milk lipidomics between NR and placebo over time will be measured by Metabolon from samples collected on study days.	Milk samples will be collected on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Difference in serum prolactin levels at day 18 and the change from the baseline between NR and placebo ( optional participation)	Blood will be collected ( optional participation) on two occasions to look at the difference in serum prolactin levels between the Nicotinamide Riboside supplementation group and the placebo.	Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]
Difference in plasma lipidomics between NR and placebo(optional participation).	Plasma samples will be analyzed using Metabolon's lipodomics platform to assess the effect of nicotinamide riboside ( NR) versus placebo on lipid metabolism. (Optional participation)	Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]
Difference in NAD+-related precursors and intermediates in K2 EDTA whole blood (optional participation) between NR and placebo over time.	The difference in NAD+-related precursors and intermediates in K2 EDTA whole blood will be measured by NADMED between NR and placebo over time.	Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]
Difference in serum metabolites between NR and placebo (optional participation).	Change in Serum NMR metabolites( analyzed by NMR-based metabolomics) will be compared between the nicotinamide riboside and placebo groups.	Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]
Feasibility metrics include supplement compliance, milk sample collection adherence, and withdrawal.	Proportion of enrolled mothers who adhere to the protocol without major deviations.	Total Day 18 + 2 days from the day of enrollment [Day 18-20]
Difference in the concentration of CCN3 in milk between NR and placebo over time.	Concentration of CCN3 in milk between NR and placebo over time using quantitative ELISA.	Milk samples will be collected on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Difference in human milk protein, carbohydrate, and fat concentrations between NR and placebo over time.	Differences in human milk protein, carbohydrate, and fat concentrations will be measured by Miris HMA™between NR and placebo over time.	Milk samples will be collected on study Day 0 + 3 days [baseline, pre-intervention], Study Day 10 ± 1 days [mid-intervention], and study Day 17 + 2 days [end of intervention].
Relationship between infant feeding practices and levels of plasma insulin, plasma amino acid, and plasma glucose in infant blood.	Plasma insulin in an infant's blood will be measured from the remnant blood sample in the lab, if any, without having to do an extra blood draw from the infant for the study.	Day 1 of life- duration of NICU stay.
Relationship between infant feeding practices and levels of metabolites in infant blood.	The relationship between infant feeding practices will be compared with levels of metabolites measured by NMR metabolomics in infant blood from any remnant blood sample for the infant in the lab, without having to do an additional blood draw for the study.	Day 1 of life to the duration of NICU stay.
Feasibility of supplement compliance and milk sample collection adherence, and withdrawal from the study	Proportion of enrolled mothers who adhere to the protocol without major deviations.	Study start to end of study
Difference in maternal serum CCN3 between NR and placebo (Optional Participation)	Difference in maternal serum CCN3 between NR and placebo at baseline and Day 18.	Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in maternal weight (lbs.)	This exploratory outcome measures change in maternal weight from baseline to the end of the study in participants receiving nicotinamide riboside versus placebo, measured using a calibrated digital scale at each study visit.	Study Day 3 ± 1 days [randomization, pre-intervention visit] and Study Day 18 + 2 days [end of study visit]
Outcome of growth parameters: Infant length (cm), weight(g), and head circumference ( cm).	This exploratory outcomes measure the changes in growth parameters (height, weight, and head circumference) using calculated z-scores (as measured by standard deviations from the mean, presented in percentages relative to the average for age).	Day 1 - Day 28
NICU outcomes	NICU outcomes accessible in the EMR include morbidity, death, necrotizing enterocolitis, chronic lung disease, retinopathy of prematurity, and sepsis.	Day 1 of life - end of NICU visit.
Difference in the concentration of urinary metabolites, including NAD+-specific metabolites as a proxy of NR supplementation, between NR and placebo over time.	Urinary metabolites will be measured using nuclear magnetic resonance (NMR)-based metabolomics between the nicotinamide riboside (NR) and placebo groups.	Urine samples will be collected on two occasions, Study Day 3 ± 1 days [Randomization visit] and Study Day 18 + 2 days [End of study visit ]
Difference in serum biomarkers of liver function and calcium between NR and placebo (optional participation).	Differences in serum biomarkers of liver function (AST/ALT) and calcium will be measured via a CMP between NR and placebo.	Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]
Diet, health, and anthropometric outcomes reported by mothers when their child turns 1, 2, and 3 years of age.	These will be obtained as a complete three-brief (10-15 minute) phone interviews when their child turns 1, 2, and 3 years old. Each call, conducted by study personnel after the child's annual well-child visit, will include a semi-structured survey about the child's diet, general health, and growth (weight, height, etc.). Participants will receive a $25 Amazon e-gift card for each completed interview (up to $75 total). Mothers may choose to complete one, two, or all three interviews.	Day 1 of life to 3 years of age for the child.

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: ChromaDex, Inc.
• Investigators: Principal Investigator: Kara Khun-Riordon, MD, UC Davis; Principal Investigator: Nicole Cacho, DO, UC Davis; Principal Investigator: Luna Khanal, MD, UC Davis

Publications and helpful links

General Publications

• Foong SC, Tan ML, Foong WC, Marasco LA, Ho JJ, Ong JH. Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants. Cochrane Database Syst Rev. 2020 May 18;5(5):CD011505. doi: 10.1002/14651858.CD011505.pub2.
• Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018 Mar 29;9(1):1286. doi: 10.1038/s41467-018-03421-7.
• Yang D, Wan Y. NR Supplementation During Lactation: Benefiting Mother and Child. Trends Endocrinol Metab. 2019 Apr;30(4):225-227. doi: 10.1016/j.tem.2019.02.004. Epub 2019 Feb 21.
• Dollerup OL, Christensen B, Svart M, Schmidt MS, Sulek K, Ringgaard S, Stodkilde-Jorgensen H, Moller N, Brenner C, Treebak JT, Jessen N. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. 2018 Aug 1;108(2):343-353. doi: 10.1093/ajcn/nqy132.
• Damgaard MV, Treebak JT. What is really known about the effects of nicotinamide riboside supplementation in humans. Sci Adv. 2023 Jul 21;9(29):eadi4862. doi: 10.1126/sciadv.adi4862. Epub 2023 Jul 21.
• Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948.
• Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep. 2019 Jul 5;9(1):9772. doi: 10.1038/s41598-019-46120-z.
• Ear PH, Chadda A, Gumusoglu SB, Schmidt MS, Vogeler S, Malicoat J, Kadel J, Moore MM, Migaud ME, Stevens HE, Brenner C. Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring. Cell Rep. 2019 Jan 22;26(4):969-983.e4. doi: 10.1016/j.celrep.2019.01.007.
• Moller L, Crone KL, Mortensen N. [Brucellosis: 3 imported cases]. Ugeskr Laeger. 1985 Jul 1;147(27):2164-6. No abstract available. Danish.
• Shen Q, Khan KS, Du MC, Du WW, Ouyang YQ. Efficacy and Safety of Domperidone and Metoclopramide in Breastfeeding: A Systematic Review and Meta-Analysis. Breastfeed Med. 2021 Jul;16(7):516-529. doi: 10.1089/bfm.2020.0360. Epub 2021 Mar 25.
• Hussain NHN, Noor NM, Ismail SB, Zainuddin NA, Sulaiman Z. Metoclopramide for Milk Production in Lactating Women: A Systematic Review and Meta-Analysis. Korean J Fam Med. 2021 Nov;42(6):453-463. doi: 10.4082/kjfm.20.0238. Epub 2021 Nov 20.
• Campbell-Yeo ML, Allen AC, Joseph KS, Ledwidge JM, Caddell K, Allen VM, Dooley KC. Effect of domperidone on the composition of preterm human breast milk. Pediatrics. 2010 Jan;125(1):e107-14. doi: 10.1542/peds.2008-3441. Epub 2009 Dec 14.
• Grzeskowiak LE, Smithers LG, Amir LH, Grivell RM. Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis. BJOG. 2018 Oct;125(11):1371-1378. doi: 10.1111/1471-0528.15177. Epub 2018 Mar 27.
• Grzeskowiak LE, Wlodek ME, Geddes DT. What Evidence Do We Have for Pharmaceutical Galactagogues in the Treatment of Lactation Insufficiency?-A Narrative Review. Nutrients. 2019 Apr 28;11(5):974. doi: 10.3390/nu11050974.
• Kwan SH, Abdul-Rahman PS. Clinical Study on Plant Galactagogue Worldwide in Promoting Women's Lactation: a Scoping Review. Plant Foods Hum Nutr. 2021 Sep;76(3):257-269. doi: 10.1007/s11130-021-00901-y. Epub 2021 Jul 22.
• Zukova S, Krumina V, Buceniece J. Breastfeeding preterm born infant: Chance and challenge. Int J Pediatr Adolesc Med. 2021 Jun;8(2):94-97. doi: 10.1016/j.ijpam.2020.02.003. Epub 2020 Feb 6.
• https://doi.org/10.1542/peds.2008-3441
• https://www.nadmed.com/wp-content/uploads/2025/03/RUO_Qualio-IFU-NAD-and-NADH-blood-v8.0-1.pdf
• Babey ME, Krause WC, Chen K, Herber CB, Torok Z, Nikkanen J, Rodriguez R, Zhang X, Castro-Navarro F, Wang Y, Wheeler EE, Villeda S, Leach JK, Lane NE, Scheller EL, Chan CKF, Ambrosi TH, Ingraham HA. A maternal brain hormone that builds bone. Nature. 2024 Aug;632(8024):357-365. doi: 10.1038/s41586-024-07634-3. Epub 2024 Jul 10.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

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 (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Feasibility trial; Nicotinamide Riboside; Neonatal intensive care unit; milk volume; Galactagogue
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Micronutrients; Vitamin B Complex; Vitamins; Vasodilator Agents; Hypolipidemic Agents; Lipid Regulating Agents; nicotinamide-beta-riboside
• Other Study ID Numbers: 1557473

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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