Investigate the Efficacy of Using NMN to Improve Embryo Development Capacity.

NCT ID: NCT06629636

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-20
• Study Completion Date: 2026-12-31

Brief Summary

The objective of this study is to investigate the efficacy of NMN supplementation in enhancing embryo developmental capacity and improving IVF success rates in patients experiencing IVF failures.

Detailed Description

Reproductive aging is an irreversible process characterized by a decline in oocyte quality, posing a significant challenge to fertility and often leading to unsuccessful outcomes in assisted reproductive technologies. Repeated ART failures can result in substantial burdens for patients, both financially and emotionally. Extensive clinical and preclinical data have established a strong correlation between age-related decline in egg quality and mitochondrial deterioration, resulting in decreased energy production within oocytes. Notably, a reduction in nicotinamide adenine dinucleotide (NAD+ / NADH) concentrations, a crucial redox cofactor and enzyme-substrate essential for energy metabolism, DNA repair, and epigenetic homeostasis, has been observed in various tissues with age.

Recent studies on mice have indicated that Nicotinamide mononucleotide supplementation may mitigate the age-related decline in NAD(P)H levels, enhancing the quality of aged oocytes. This improvement is achieved by promoting both nuclear and cytoplasmic maturation, ensuring euploidy and fertilization competence, ultimately leading to an increased ovulation rate and improved fertility. Moreover, NMN has been shown to restore mitochondrial function in aged oocytes, effectively suppressing the accumulation of reactive oxygen species and DNA damage, and subsequently reducing apoptosis.

Clinical studies have further corroborated the safety and tolerability of NMN supplementation, with daily oral doses of up to 900 mg demonstrating an increase in blood NAD concentrations. Furthermore, research suggests that a daily oral dose of 900 mg maximizes clinical efficacy, as evidenced by blood NAD concentration and physical performance.

This study adopts a triple-blind, randomized, placebo-controlled, prospective pilot study design. This prospective study aims to evaluate the effects of dietary supplementation with 900mg of NMN on ART outcomes in individuals experiencing in vitro fertilization failures attributed to compromised oocyte and embryo quality.

Conditions

Repeated IVF Failure; Female Infertility

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

NMN intervention

NMN capsules (total of 900mg/day) for 8 weeks

Group Type: ACTIVE_COMPARATOR

NMN capsule

Intervention Type: DIETARY_SUPPLEMENT

Total of 900mg/day for 8 weeks

Placebo intervention

NMN-free placebo capsules for 8 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

NMN-free placebo capsules for 8 weeks

Interventions

NMN capsule

Total of 900mg/day for 8 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo

NMN-free placebo capsules for 8 weeks

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Agree to participate in the study
• 32-42 years old
• Having at least one previous embryo implantation failure
• History of low Embryo quality at day3 or day5 (according to Veeck's and Gardner's Criteria)
• No major uterine or ovarian abnormalities
• BMI level 18-25kg/m2

Exclusion Criteria

• Ovarian endometriosis with Chocolate cysts (AFS type 3 and 4)
• Patients who have taken different supplements such as coenzyme Q10, vitamin E, carnitine,niacin, nicotinamide, or other vitamin B3-related etc. within the previous month
• Any medical contraindication of oocyte retrieval or subsequent procedures
• Couples where the husband presents with severe sperm abnormalities
• Couples where the husband presents <5 million/mL motile sperm
• Uterine structural anomalies
• Polycystic ovaries
• Premature ovarian failure
• Individuals who need regular medication to treat chronic diseases such as diabetes, hypertension, gout, hyperuricemia, etc.
• Individuals who need drug treatment for any mental illness such as epilepsy and depression.
• Individuals who suffer from infectious diseases such as hepatitis B, active tuberculosis, AIDS, etc.
• Cancer patients or receiving chemo/radiotherapy treatment within the past 3 years.

• Minimum Eligible Age: 32 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Abinopharm, Inc

NETWORK

Sponsor Role: collaborator

Aba Chemicals Co Ltd

UNKNOWN

Sponsor Role: collaborator

Sunkaky Medical Cooperation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yoshiharu M., Yoshiharu Morimoto, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sankaky Medical Corporation

Naoharu M., Naoharu Yoshiharu, MD

Role: STUDY_DIRECTOR

Sankaky Medical Corporation

Locations

IVF Namba Clinic, Sankaky Medical Corporation

Osaka, Osaka, Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Udayanga KGS., Udayanga Gamage, BVSc, PhD

Role: CONTACT

udayanga646@ivfjapan.com

+81 90 9823 8477

Masaya Y., Masaya Yamanaka, BSc

Role: CONTACT

yamanaka086@ivfjapan.com

+81 80 4344 2654

Facility Contacts

Naoharu M., Naoharu Morimoto, MD

Role: primary

morimoto003@ivfjapan.com

+81 6 6534 8824

References

Huang H. A Multicentre, Randomised, Double Blind, Parallel Design, Placebo Controlled Study to Evaluate the Efficacy and Safety of Uthever (NMN Supplement), an Orally Administered Supplementation in Middle Aged and Older Adults. Front Aging. 2022 May 5;3:851698. doi: 10.3389/fragi.2022.851698. eCollection 2022.

Reference Type: BACKGROUND

PMID: 35821806 (View on PubMed)

Yi L, Maier AB, Tao R, Lin Z, Vaidya A, Pendse S, Thasma S, Andhalkar N, Avhad G, Kumbhar V. The efficacy and safety of beta-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023 Feb;45(1):29-43. doi: 10.1007/s11357-022-00705-1. Epub 2022 Dec 8.

Reference Type: BACKGROUND

PMID: 36482258 (View on PubMed)

Miao Y, Cui Z, Gao Q, Rui R, Xiong B. Nicotinamide Mononucleotide Supplementation Reverses the Declining Quality of Maternally Aged Oocytes. Cell Rep. 2020 Aug 4;32(5):107987. doi: 10.1016/j.celrep.2020.107987.

Reference Type: BACKGROUND

PMID: 32755581 (View on PubMed)

Bertoldo MJ, Listijono DR, Ho WJ, Riepsamen AH, Goss DM, Richani D, Jin XL, Mahbub S, Campbell JM, Habibalahi A, Loh WN, Youngson NA, Maniam J, Wong ASA, Selesniemi K, Bustamante S, Li C, Zhao Y, Marinova MB, Kim LJ, Lau L, Wu RM, Mikolaizak AS, Araki T, Le Couteur DG, Turner N, Morris MJ, Walters KA, Goldys E, O'Neill C, Gilchrist RB, Sinclair DA, Homer HA, Wu LE. NAD+ Repletion Rescues Female Fertility during Reproductive Aging. Cell Rep. 2020 Feb 11;30(6):1670-1681.e7. doi: 10.1016/j.celrep.2020.01.058.

Reference Type: BACKGROUND

PMID: 32049001 (View on PubMed)

Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It's Destroyed. Cell Metab. 2016 Jun 14;23(6):965-966. doi: 10.1016/j.cmet.2016.05.022.

Reference Type: BACKGROUND

PMID: 27304496 (View on PubMed)

Bentov Y, Yavorska T, Esfandiari N, Jurisicova A, Casper RF. The contribution of mitochondrial function to reproductive aging. J Assist Reprod Genet. 2011 Sep;28(9):773-83. doi: 10.1007/s10815-011-9588-7. Epub 2011 May 27.

Reference Type: BACKGROUND

PMID: 21617930 (View on PubMed)

Hashimoto S, Morimoto Y. Mitochondrial function of human embryo: Decline in their quality with maternal aging. Reprod Med Biol. 2022 Dec 21;21(1):e12491. doi: 10.1002/rmb2.12491. eCollection 2022 Jan-Dec.

Reference Type: BACKGROUND

PMID: 36570768 (View on PubMed)

Other Identifiers

IVFJapan202402

Identifier Type: -

Identifier Source: org_study_id