Nicotinamide Riboside for Low Milk Supply

(MOONRISE Trial)

Overseen By Bruce German, PhD

Age: Any Age

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: University of California, Davis

Must not be taking: Narcotics, Amphetamines, Contraceptives, others

Disqualifiers: Breast surgery, Cancer treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a supplement called nicotinamide riboside (NR) can help mothers of very premature infants produce more breast milk. Researchers believe NR boosts metabolism, potentially supporting the energy demands of breastfeeding. Participants will receive either NR (nicotinamide riboside chloride) or a placebo at different times to assess its impact on milk supply. The study seeks mothers whose babies were born at or before 28 weeks and who are willing to measure their milk volume.

As a Phase 2, Phase 3 trial, this study aims to evaluate NR's effectiveness in an initial group and is in the final step before FDA approval. It offers participants a chance to contribute to important advancements in maternal and infant health.

Will I have to stop taking my current medications?

The trial requires that you stop using narcotics, amphetamines, cancer treatments, lithium, gold therapies, contraceptives, and galactagogues (substances that increase milk supply). If you are taking any of these, you would need to stop before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotinamide riboside (NR) is generally safe for people. The FDA has labeled NR as "Generally Recognized As Safe" (GRAS) for use in food, indicating low toxicity in short-term studies. Simply put, NR hasn't shown harmful effects in the short term.

NR occurs naturally in cow's milk and aids in producing NAD+, a substance crucial for energy and metabolism. While specific studies on NR's effects on milk supply in women are lacking, animal studies have shown positive results. For example, studies with lactating rats found that NR increased both the amount and quality of milk without causing harm.

These early findings are encouraging, but consulting a healthcare provider before joining a clinical trial is always wise to understand any potential health risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nicotinamide Riboside (NR) is unique because it offers a new approach to addressing low milk supply by potentially enhancing cellular energy production. Unlike existing treatments that might focus on hormonal or herbal solutions, NR is a form of vitamin B3 that works at the cellular level to boost NAD+ levels, which are crucial for energy metabolism. Researchers are excited about NR because it could offer a more direct and efficient way to support breastfeeding mothers, potentially leading to faster and more sustainable improvements in milk production.

What evidence suggests that nicotinamide riboside might be an effective treatment for low milk supply?

Research has shown that nicotinamide riboside (NR) might help increase milk production. In studies with breastfeeding rats, NR boosted milk output by 31%, from 13.7 kg to 18.0 kg each day. It also increased key nutrients like NAD+ in the milk, which provides energy for breastfeeding. Although more research is needed in humans, these animal study results are encouraging. In this trial, some participants will receive NR first, while others will start with a placebo. NR may offer health benefits for mothers and could help improve milk supply for premature babies. ^{4 5 6 7 8}

Who Is on the Research Team?

Kara Khun-Riordon, MD

Principal Investigator

UC Davis

Nicole Cacho, DO

Principal Investigator

UC Davis

Luna Khanal, MD

Principal Investigator

UC Davis

Are You a Good Fit for This Trial?

This trial is for mothers who have given birth to extremely preterm infants (≤28 weeks gestation) at UC Davis Medical Center or transferred there within 6 days of birth. Participants must consent and be willing to express and measure milk volume.

Inclusion Criteria

My baby was born at or before 28 weeks of pregnancy.

Informed consent for participation of both mother and baby

Infant born at the UC Davis Medical Center or transferred to the UC Davis Medical Center NICU within the first 6 days of life

Exclusion Criteria

Mother plans to use any form of galactagogue (including fenugreek)

My mother cannot give her consent.

Mother is actively using narcotics or amphetamines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Intervention Phase 1

Mothers receive either NR or placebo for 7 days

7 days

Daily monitoring in NICU

Washout Period

A washout period between intervention phases

7 days

Intervention Phase 2

Mothers receive the opposite treatment (NR or placebo) for 7 days

7 days

Daily monitoring in NICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside Chloride
• Placebo

Trial Overview The study tests if nicotinamide riboside (NR), a supplement, can increase breast milk production in these mothers. It involves two phases: one with NR supplementation and the other with a placebo, each assigned randomly.

How Is the Trial Designed?

Group I: Placebo First Experimental Treatment 2 Interventions

Mothers will receive placebo during the first 7 days of intervention, then NR for the 7 days following washout.

Group II: NR First Experimental Treatment 2 Interventions

Mothers will receive NR during the first 7 days of intervention, then placebo for the 7 days following washout.

Nicotinamide Riboside Chloride is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Nicotinamide Riboside Chloride for:

• Food supplements
• Foods for special medical purposes (FSMP)
• Total Diet Replacements Products for Weight Control (TDRWC)

Approved in United States as Nicotinamide Riboside Chloride for:

• Dietary supplements

Approved in Canada as Nicotinamide Riboside Chloride for:

• Licensed Natural Health Products

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Published Research Related to This Trial

Nicotinamide riboside hydride (NRH) is identified as a more effective and faster precursor for NAD+ synthesis compared to nicotinamide riboside (NR), utilizing a unique NRK1-independent pathway for NAD+ production.

NRH is orally bioavailable in mice and has shown potential in preventing acute kidney injury caused by cisplatin, suggesting its therapeutic promise in enhancing NAD+ levels and addressing metabolic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. Giroud-Gerbetant, J., Joffraud, M., Giner, MP., et al.[2021]

Nicotinamide riboside (NR), a form of vitamin B3, was found to be safe in various toxicity studies, including a 90-day rat study, with no genotoxic effects and no mortality at high doses (5000 mg/kg).

The lowest observed adverse effect level for NR was determined to be 1000 mg/kg/day, indicating that while it is generally safe, higher doses may lead to toxicity in organs such as the liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. Conze, DB., Crespo-Barreto, J., Kruger, CL.[2019]

Nicotinamide riboside chloride is considered safe for use in food supplements at levels up to 300 mg/day for healthy adults, with no safety concerns raised from human studies or animal data.

The substance effectively contributes to the body's nicotinamide levels and is bioavailable, making it a viable source of niacin, although caution is advised for pregnant and lactating women due to insufficient safety data for these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. Turck, D., Castenmiller, J., de Henauw, S., et al.[2020]

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Conze, D., Brenner, C., Kruger, CL.[2023]

Nicotinamide riboside (NR) is a promising NAD+ precursor that has shown potential health benefits in treating various conditions, including cardiovascular, neurodegenerative, and metabolic disorders, based on numerous animal and human studies.

Research indicates that NR may also have therapeutic applications against infections, such as SARS-CoV-2, but challenges related to its bioavailability and safety need to be addressed for effective translation into clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Mehmel, M., Jovanović, N., Spitz, U.[2021]

The EFSA Panel concluded that the safety of nicotinamide riboside chloride (NRC) has not been established for use in meal replacement products and nutritional drink mixes at proposed levels of 300 mg/day, due to concerns about potential adverse effects, especially in infants.

For food for special medical purposes and total diet replacement for weight control, NRC is considered as safe as pure nicotinamide at a maximum intake of 210 mg/day, which is below the established upper limit of 900 mg/day for adults, but further research is needed to assess long-term safety and potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2021]

Nicotinamide riboside (NR) is a form of vitamin B3 that effectively increases NAD+ levels, which may help counteract age-related declines in this important metabolite.

In a 90-day safety study on Sprague Dawley rats, NR-E showed no significant adverse effects at doses up to 1,200 mg/kg/d, establishing a no-observed-adverse-effect-level (NOAEL) of 500 mg/kg/d for males and 1,200 mg/kg/d for females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. Marinescu, AG., Chen, J., Holmes, HE., et al.[2021]

Citations

1. moonrise.ucdavis.edu moonrise.ucdavis.edu/

Milk Volume Outcomes Following Oral Nicotinamide Riboside ... We hypothesize that the supplement could be similarly effective in humans. In the MOONRISE study, we will investigate the effect of a standard dose of NR versus ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022316625003736

NAD+ Repletion Enhances Mammary Lactogenesis and ... NR upregulated mammary and milk NAD+ levels (+ 38% and + 256%, P < 0.05), alongside 31% more milk daily yield (18.0 compared with 13.7 kg, P < 0.05).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10780616/

Effect of Nicotinamide Mononucleotide Concentration in ... The supplementation of NR to the mother has been shown to be effective in increasing infant neurodevelopment, but increases in NMN levels related to NR ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04614714

Milk Volume Outcomes Following Oral Nicotinamide ... In lactating rats, NR supplementation improved milk quantity and quality, with metabolic benefits for the mother and lasting protective advantages for the ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04614714/milk-volume-outcomes-following-oral-nicotinamide-riboside-supplementation-in-mothers-of-extremely-preterm-infants?id=729&slug=lactation-insufficiency

Milk Volume Outcomes Following Oral Nicotinamide ... In lactating rats, NR supplementation improved milk quantity and quality, with metabolic benefits for the mother and lasting protective ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6611812/

Safety and Metabolism of Long-term Administration of ... Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. The Journal of nutrition. 2016;146:957–963. doi: 10.3945/jn.116.230078 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7352172/

Nicotinamide Riboside—The Current State of Research and ... In mice models, NR can increase NAD+ metabolism and thereby improve glucose tolerance, reduce weight gain, and exhibit neuroprotective effects against diabetic ...

8. fda.gov fda.gov/files/food/published/GRAS-Notice-000635--Nicotinamide-riboside-chloride.pdf

GRAS Notice 635: Nicotinamide riboside chloride CORROBORATIVE SAFETY DATA ON NICOTINAMIDE ........... ... Available data indicate that they are less toxic in acute or short-term studies ...