Tracing the Metabolic Flux of Orally Administered NAD+ Precursors

NCT06882096 | Recruiting Phase 1 DMC

• 1 other identifier: MBT-1918/1932-MET
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

We are doing this research to learn how healthy younger and older adults use two forms of vitamin B3-called nicotinamide mononucleotide (NMN) and nicotinamide (NAM)-to make NAD+. NAD+ is a natural substance that cells need for energy and other important processes. Our goal is to find out how these NAD precursors are absorbed and metabolized and how they raise NAD+ in different tissues. Who can join? Healthy adults men and women aged 18 to 40 (younger group) or 65 and older (older group) Participants with a body mass index ranging between 19 and 35 No major health issues like diabetes or severe kidney disease What will happen? Participants will take labeled or unlabeled NMN or NAM by mouth every day for 14 days. Researchers will collect blood, urine, and stool samples. Researchers also do a small muscle biopsy (under local numbing) twice to check how these NAD precursors raise NAD+ in muscle. Why is this important? NAD+ levels may drop as people age, and this drop could affect overall health and energy in cells. A better understanding of how NMN and NAM are metabolized in the body to raise NAD+ levels in both younger and older adults may help us optimize dosing and strategies for raising NAD in older people. Possible benefits and risks: Participants may not get any direct health benefit from this study; the main goal is to gather new knowledge. NMN and NAM appear safe in the doses used. A muscle biopsy may cause soreness or bruising. Researchers will monitor participants closely for any side effects throughout the study.

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (1)

• Labelled NAD+ in Peripheral Blood

  Quantify the fraction of peripheral blood. NAD+ containing the stable isotope labelled tracer

  During the Study Intervention Period Day 1 through Day 14

Secondary Outcomes (13)

• Labelled NAD+ in Muscle

  During the Study Intervention Period Day 1 through Day 14

• 1-Methyl nicotinamide (MeNAM) in Plasma

  During the Study Intervention Period Day 1 through Day 14

• 1-Methyl nicotinamide (MeNAM) in Muscle

  During the Study Intervention Period Day 1 through Day 14

• 1-Methyl nicotinamide (MeNAM) in Urine

  During the Study Intervention Period Day 1 through Day 14

• 1-Methyl nicotinamide (MeNAM) in Stool

  During the Study Intervention Period Day 1 through Day 14

Study Arms (2)

NMN- Nicotinamide Mononucleotide

ACTIVE COMPARATOR

This arm will include 16 participants (8 young and 8 older adults) who will receive NMN once daily for 14 consecutive days.

Drug: Nicotinamide Mononucleotide (NMN)

NAM- Nicotinamide

ACTIVE COMPARATOR

This arm will include 16 participants (8 young and 8 older adults) who will receive NAM once daily for 14 consecutive days.

Drug: Nicotinamide (NAM)

Interventions

Nicotinamide Mononucleotide (NMN) DRUG

Nicotinamide Mononucleotide (NMN)

NMN- Nicotinamide Mononucleotide

Nicotinamide (NAM) DRUG

Nicotinamide (NAM)

NAM- Nicotinamide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A participant may be enrolled if he/she is:
• A healthy, community-living, man or a woman between 18 and 40 years, inclusive or 65 years or older
• Has a body mass index (BMI) between 19 and 35 kg/m2, inclusive
• Is free from clinically significant medical problems as determined by the Investigator
• Is capable of providing written informed consent.
• Is willing and able to provide authorization for the use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act.

You may not qualify if:

• A subject may not be enrolled if s/he:
• Has AST or ALT \> 2 times the upper limit of normal
• Hematocrit \< 36% or \> 51% for men, or \< 35% to \> 48% for women
• Diagnosis of diabetes, using diabetes medications or an A1C \> 6.4%
• Serum creatinine \> 2.0 mg/dL or eGFR \<60 mL/min
• Prohibited medications and substances: use of anabolic steroids, rhGH, DHEA, androstenedione, or any performance enhancing drug; Current use of opiates, amphetamine, cannabinoids and cocaine
• Use of any dietary supplement. Subjects who are using a supplement containing NAM (or niacin or NMN or NR) may be included if they agree to stop supplement at least 2 weeks before randomization.
• For women only: Pregnant or planning to get pregnant over the next 6 months, or lactating
• Participation in an investigational trial within the past 3 months
• Other medical conditions which, in the opinion of the investigator, would jeopardize safety or impact the validity of the study results
• For women only:
• Female of childbearing age: Use of oral contraceptives is allowed provided the contraceptive regimen was initiated at least 3 months before randomization and the participant agrees not to change the regimen during the course of the study.
• Excluded Medications and Treatments
• The ingestion of the following is prohibited during 14 days prior to Day 0 and for the duration of the intervention period:
• Products that contain niacin, nicotinic acid, nicotinamide in any form, other than natural foods

Sponsors & Collaborators

• Metro International Biotech, LLC: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Related Publications (9)

• Sauve AA, Wang Q, Zhang N, Kang S, Rathmann A, Yang Y. Triple-Isotope Tracing for Pathway Discernment of NMN-Induced NAD+ Biosynthesis in Whole Mice. Int J Mol Sci. 2023 Jul 5;24(13):11114. doi: 10.3390/ijms241311114.

  PMID: 37446292 BACKGROUND

• Amjad S, Nisar S, Bhat AA, Shah AR, Frenneaux MP, Fakhro K, Haris M, Reddy R, Patay Z, Baur J, Bagga P. Role of NAD+ in regulating cellular and metabolic signaling pathways. Mol Metab. 2021 Jul;49:101195. doi: 10.1016/j.molmet.2021.101195. Epub 2021 Feb 17.

  PMID: 33609766 BACKGROUND

• Pencina KM, Lavu S, Dos Santos M, Beleva YM, Cheng M, Livingston D, Bhasin S. MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of beta-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):90-96. doi: 10.1093/gerona/glac049.

  PMID: 35182418 BACKGROUND

• Pencina KM, Valderrabano R, Wipper B, Orkaby AR, Reid KF, Storer T, Lin AP, Merugumala S, Wilson L, Latham N, Ghattas-Puylara C, Ozimek NE, Cheng M, Bhargava A, Memish-Beleva Y, Lawney B, Lavu S, Swain PM, Apte RS, Sinclair DA, Livingston D, Bhasin S. Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. J Clin Endocrinol Metab. 2023 Jul 14;108(8):1968-1980. doi: 10.1210/clinem/dgad027.

  PMID: 36740954 BACKGROUND

• Dutta T, Kapoor N, Mathew M, Chakraborty SS, Ward NP, Prieto-Farigua N, Falzone A, DeLany JP, Smith SR, Coen PM, DeNicola GM, Gardell SJ. Source of nicotinamide governs its metabolic fate in cultured cells, mice, and humans. Cell Rep. 2023 Mar 28;42(3):112218. doi: 10.1016/j.celrep.2023.112218. Epub 2023 Mar 9.

  PMID: 36897780 BACKGROUND

• Kim LJ, Chalmers TJ, Madawala R, Smith GC, Li C, Das A, Poon EWK, Wang J, Tucker SP, Sinclair DA, Quek LE, Wu LE. Host-microbiome interactions in nicotinamide mononucleotide (NMN) deamidation. FEBS Lett. 2023 Sep;597(17):2196-2220. doi: 10.1002/1873-3468.14698. Epub 2023 Aug 9.

  PMID: 37463842 BACKGROUND

• Xiao W, Wang RS, Handy DE, Loscalzo J. NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism. Antioxid Redox Signal. 2018 Jan 20;28(3):251-272. doi: 10.1089/ars.2017.7216. Epub 2017 Jul 28.

  PMID: 28648096 BACKGROUND

• Chellappa K, McReynolds MR, Lu W, Zeng X, Makarov M, Hayat F, Mukherjee S, Bhat YR, Lingala SR, Shima RT, Descamps HC, Cox T, Ji L, Jankowski C, Chu Q, Davidson SM, Thaiss CA, Migaud ME, Rabinowitz JD, Baur JA. NAD precursors cycle between host tissues and the gut microbiome. Cell Metab. 2022 Dec 6;34(12):1947-1959.e5. doi: 10.1016/j.cmet.2022.11.004.

  PMID: 36476934 BACKGROUND

• Bhasin S, Seals D, Migaud M, Musi N, Baur JA. Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns. Endocr Rev. 2023 Nov 9;44(6):1047-1073. doi: 10.1210/endrev/bnad019.

  PMID: 37364580 BACKGROUND

MeSH Terms

Interventions

Nicotinamide Mononucleotide; Niacinamide

Intervention Hierarchy (Ancestors)

Ribonucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Shalender Bhasin, MB, BS

  Brigham and Women's Hosptial

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mohan Sonu Chandra, MB,BS

CONTACT

617-525-9154; mchandra@bwh.harvard.edu

Nancy K Latham, PhD

CONTACT

617-999-9195; nklatham@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 18, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)