Preterm BirthPhase 2/3MOONRISENCT04614714
Milk Volume Outcomes Following Oral Nicotinamide Riboside Supplementation in Mothers of Extremely Preterm Infants
A Phase 2/3 study testing Nicotinamide Riboside (NR) in people with Preterm Birth and Inadequate Milk Production, run by University of California, Davis at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth, Inadequate Milk Production
- What is being tested?
- Nicotinamide Riboside (NR)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2026to 30 Aug 2027
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, Davis
Sacramento, California, 95817
About this study
Official title: 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.
Read the 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.
- Conditions
- Preterm Birth, Inadequate Milk Production
- Being tested
- Nicotinamide Riboside (NR), Placebo
- Keywords
- Nicotinamide Riboside, milk volume, Neonatal intensive care unit, Galactagogue, Feasibility trial
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide Riboside (NR)Other
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].
PlaceboOther
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].
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide Riboside (NR) | Experimental | 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]. Receives: Other: Nicotinamide Riboside (NR) |
| Placebo | Placebo comparator | 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]. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 4 days post-delivery of the infant.
Secondary outcomes (16)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2020
- Study start19 Aug 2026
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- ChromaDex, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04614714
- Sponsor's protocol ID
- 1557473
- Acronym
- MOONRISE
- Status last verified
- Sep 2026
- First submitted
- 22 Oct 2020
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 30797625Martens 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.
PubMed 29599478Dollerup 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.
PubMed 29992272Damgaard 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.
PubMed 37478182Trammell 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.
PubMed 27721479Conze 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.
PubMed 31278280Ear 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.
PubMed 30673618Moller L, Crone KL, Mortensen N. [Brucellosis: 3 imported cases]. Ugeskr Laeger. 1985 Jul 1;147(27):2164-6. No abstract available. Danish.
PubMed 4060272Foong 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.
PubMed 32421208Shen 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.
PubMed 33769844Hussain 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.
PubMed 34871486Campbell-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.
PubMed 20008425Grzeskowiak 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.
PubMed 29469929Grzeskowiak 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.
PubMed 31035376Kwan 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.
PubMed 34292494