Effect of NMN (Nicotinamide Mononucleotide) on Diminished Ovarian Reserve (Including Premature Ovarian Insufficiency)

Study Overview
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Brief Summary
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The purpose of the study is to understand the effect of nicotinamide mononucleotide (NMN) on patients with diminished ovarian reserve (including premature ovarian insufficiency).

Detailed Description
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This study aims to evaluate the effects of NMN on reproductive endocrine, immune homeostasis, and reproductive outcomes in women with DOR (including POI), and to explore its underlying mechanisms to provide the intervention strategies for DOR (including POI).

Official Title
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Effect of NMN (Nicotinamide Mononucleotide) Intervention on Patients With Diminished Ovarian Reserve (Including Premature Ovarian Insufficiency)

Conditions
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Diminished Ovarian Reserve, Premature Ovarian Insufficiency

Intervention / Treatment
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* Dietary Supplement: NMN intervention
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who are 20 to 40 years old. The concentrations of anti-Mullerian hormone < 1.1 ng/ml, the values of antral follicle count range from less than 5 to less than 7 and two recordings of serum concentrations of day-3 follicle-stimulating hormone (FSH) ≥10 IU/L. Individuals who can insist on continuous monitoring in the outpatient clinic. Individuals who are not participating in other research projects currently or 3 months before the intervention. Exclusion Criteria: Individuals who are during pregnant, lactation or menopause. Individuals who had non-46-XX karyotype, or attributed to known genetic etiology. Individuals who had pelvic surgery. Cancer patients or receiving chemo/radiotherapy treatment within the past 5 years. Individuals who need regular medication to treat chronic diseases such as diabetes, hypertension, gout, hyperuricemia, etc. Individuals who currently receiving weight-loss drugs or surgery or within the past 2 months. Use of medications or traditional Chinese medicine that affect hormone levels, appetite, carbohydrate absorption, and metabolism within the past 3 months. Individuals who take niacin, nicotinamide, or other vitamin B3-related supplementation, or other supplementation such as coenzyme Q10, vitamin E currently or within the past 3 months. Use of antibiotics, probiotics, or prebiotics that affect the flora within the past 3 months. Individuals with severe liver diseases or kidney disease that are ineligible to participate in the study. A medical history of severe cardiovascular and cerebrovascular diseases. Individuals who currently suffer from severe gastrointestinal diseases or undergo gastrointestinal resection that may affect nutrient absorption. Individuals who drink more than 15g of alcohol per day or have a smoking habit. 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. Unable or unwilling to follow the study protocol.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMN intervention<br>3 months of NMN | Dietary Supplement: NMN intervention<br>* NMN capsules (total of 600mg/day) for 3 months<br>|
| Placebo Comparator: Placebo<br>3 months of NMN-free placebo | Other: Placebo<br>* NMN-free placebo capsules for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The comparison of the gut microbiota composition | Determination the gut microbiota composition change of stool samples between placebo group and intervention group by 16S metagenomic. | before and after 2, 8, 12 weeks of intervention | 
| The alterations of gut metabolites | Determination the alterations of gut metabolites before and after NMN intervention by metabolomics. | before and after 2, 8, 12 weeks of intervention | 
| Blood sugar level | Changes in plasma glucose concentration after the intervention. | before and after 2, 8, 12 weeks of intervention | 
| Fasting insulin | Changes in plasma insulin concentration after the intervention. | before and after 2, 8, 12 weeks of intervention | 
| Endocrine hormones including AMH | Changes in endocrine hormones including AMH levels in serum after the intervention. | before and after 3 months of intervention | 
| Ovarian volume | The size of each ovary will be determined using transvaginal ultrasonography for each participant in early follicular phase. | before and after 3 months of intervention | 
| Follicle number | The number of all antral follicles in each ovary will be determined using transvaginal ultrasonography for each participant. | before and after 3 months of intervention | 
| Blood NAD+ level | Changes in whole blood NAD+ level after the intervention. | before and after 2, 8, 12 weeks of intervention | 
| Changes in NAD-related metabolites in urine | Determination the changes of NAD-related metabolites in urine before and after NMN intervention by metabolomics. | before and after 2, 8, 12 weeks of intervention |