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

Study Overview
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Brief Summary
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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.

Official Title
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Nicotinamide Riboside and Milk Production in the NICU

Conditions
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Preterm Birth, Inadequate Milk Production

Intervention / Treatment
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* Drug: Nicotinamide riboside chloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |