Preterm Birth, Inadequate Milk Production
Conditions
Keywords
Nicotinamide Riboside, milk volume, Neonatal intensive care unit, Galactagogue, Feasibility trial
Brief 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.
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.
Interventions
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 \[D17-19\].
OTHERPlacebo
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 \[D17-19\].
Sponsors
University of California, Davis
ChromaDex, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of enrollment in a double-blind placebo-controlled supplementation trial in mothers of infants who are hospitalized. | Within 4 days post-delivery of the infant. | Proportion of eligible mothers who consent to enrollment in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in mean milk volume of expressed milk (mL) between NR and 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]. | Comparison of total 24-hour expressed breast milk volume (in milliliters) between mothers receiving nicotinamide riboside and those receiving placebo. |
| Difference in human milk micronutrient concentrations 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]. | 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. |
| Difference in amount and diversity of metabolites, including NAD+-related precursors and intermediates in milk 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]. | 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. |
| Difference in human milk glycans (HMOs, glycoproteins, glycolipids) 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]. | 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. |
| Difference in milk lipidomics in milk 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]. | The difference in milk lipidomics between NR and placebo over time will be measured by Metabolon from samples collected on study days. |
| Difference in serum prolactin levels at day 18 and the change from the baseline between NR and placebo ( optional participation) | Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit] | 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. |
| Difference in plasma lipidomics between NR and placebo(optional participation). | Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit] | 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) |
| Difference in NAD+-related precursors and intermediates in K2 EDTA whole blood (optional participation) between NR and placebo over time. | Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit] | The difference in NAD+-related precursors and intermediates in K2 EDTA whole blood will be measured by NADMED between NR and placebo over time. |
| Difference in serum metabolites between NR and placebo (optional participation). | Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit] | Change in Serum NMR metabolites( analyzed by NMR-based metabolomics) will be compared between the nicotinamide riboside and placebo groups. |
| Feasibility metrics include supplement compliance, milk sample collection adherence, and withdrawal. | Total Day 18 + 2 days from the day of enrollment [Day 18-20] | Proportion of enrolled mothers who adhere to the protocol without major deviations. |
| Difference in the concentration of CCN3 in milk 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]. | Concentration of CCN3 in milk between NR and placebo over time using quantitative ELISA. |
| Difference in human milk protein, carbohydrate, and fat concentrations 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]. | Differences in human milk protein, carbohydrate, and fat concentrations will be measured by Miris HMA™between NR and placebo over time. |
| Relationship between infant feeding practices and levels of plasma insulin, plasma amino acid, and plasma glucose in infant blood. | Day 1 of life- duration of NICU stay. | 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. |
| Relationship between infant feeding practices and levels of metabolites in infant blood. | Day 1 of life to the duration of NICU stay. | 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. |
| Feasibility of supplement compliance and milk sample collection adherence, and withdrawal from the study | Study start to end of study | Proportion of enrolled mothers who adhere to the protocol without major deviations. |
| Difference in maternal serum CCN3 between NR and placebo (Optional Participation) | Study Day 3 + 1/-3 days [baseline] and Study Day 18 + 2/-1 days [end of study visit] | Difference in maternal serum CCN3 between NR and placebo at baseline and Day 18. |
Countries
United States
Contacts
CONTACTNicole Cacho, DO
CONTACTKara Kuhn Riordon, MD
Outcome results
None listed