Identifying Molecular Determinants of Infertility in Men (MODIFY)

Male Infertility Clinical Trial

Official title:

Identifying Molecular Determinants of Infertility in Men (MODIFY)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06147700
• Other study ID #: 2023-085
• Status: Recruiting
• Start date: October 11, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: Singapore Institute for Clinical Sciences
• Contact: Candida Vaz
• Phone: 8854 6302
• Email: candida_vaz[@]sics.a-star.edu.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to understand the underlying mechanisms of infertility caused by unknown factors. The investigator propose to identify small non-coding RNA (sncRNA) biomarkers of infertility and advance towards developing a more accurate and robust approach for infertility diagnosis.

Description:

The goal of the study is to identify small non-coding RNA signatures of infertility in men through the comparison of sperm sncRNA profiles from around 100 men (21-50 years of age). The participants will be classified into fertile and infertile groups by the conventional method.

Through the project, the investigator intends to understand the underlying mechanisms of idiopathic infertility. By utilizing semen as liquid biopsy, through sperm sncRNA profiling and comparison (infertile vs fertile). The investigator proposes to identify the sncRNA (miRNAs, piRNAs and tRFs) as biomarkers of infertility.

The investigator proposes to generate a validated signature of sncRNAs that will help in selecting high quality sperms for IVF.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Gender: Male
• Age group: 21 Years to 50 Years

Eligibility

Inclusion Criteria

• Male, aged 21 - 50 years old

• Proficient in English language

• Willing to comply to study protocol

• Able to provide written informed consent

Exclusion Criteria

• Current and/or previous diagnosis of Tuberculosis, Acquired immunodeficiency syndrome (AIDs), and other sexually transmitted diseases

• Experiencing severely limited mobility (eg. Wheelchair bound, need walking aid)

• Diagnosed with severe unstable mental conditions (eg. Dementia, or cognitive impairment)

• Alcohol or drug abuse

Related Conditions & MeSH terms

• Infertility
• Infertility, Male
• Male Infertility

Locations

Country	Name	City	State
Singapore	Human Development Research Centre (HDRC)	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Singapore Institute for Clinical Sciences

Country where clinical trial is conducted

Singapore, 

References & Publications (9)

Abu-Halima M, Hammadeh M, Backes C, Fischer U, Leidinger P, Lubbad AM, Keller A, Meese E. Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertil Steril. 2014 Oct;102(4):989-997.e1. doi: 10.1016/j.fertnstert.2014.07.001. Epub 2014 Aug 6. — View Citation

Alves MBR, Celeghini ECC, Belleannee C. From Sperm Motility to Sperm-Borne microRNA Signatures: New Approaches to Predict Male Fertility Potential. Front Cell Dev Biol. 2020 Aug 21;8:791. doi: 10.3389/fcell.2020.00791. eCollection 2020. — View Citation

Cao XW, Lin K, Li CY, Yuan CW. [A review of WHO Laboratory Manual for the Examination and Processing of Human Semen (5th edition)]. Zhonghua Nan Ke Xue. 2011 Dec;17(12):1059-63. Chinese. — View Citation

Cui L, Fang L, Shi B, Qiu S, Ye Y. Spermatozoa micro ribonucleic acid-34c level is correlated with intracytoplasmic sperm injection outcomes. Fertil Steril. 2015 Aug;104(2):312-7.e1. doi: 10.1016/j.fertnstert.2015.05.003. Epub 2015 Jun 6. — View Citation

Donkin I, Barres R. Sperm epigenetics and influence of environmental factors. Mol Metab. 2018 Aug;14:1-11. doi: 10.1016/j.molmet.2018.02.006. Epub 2018 Feb 27. — View Citation

Hua M, Liu W, Chen Y, Zhang F, Xu B, Liu S, Chen G, Shi H, Wu L. Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization. Cell Discov. 2019 Apr 9;5:20. doi: 10.1038/s41421-019-0087-9. eCollection 2019. No abstract available. — View Citation

Soubry A. POHaD: why we should study future fathers. Environ Epigenet. 2018 Apr 26;4(2):dvy007. doi: 10.1093/eep/dvy007. eCollection 2018 Apr. — View Citation

Vashisht A, Gahlay GK. Using miRNAs as diagnostic biomarkers for male infertility: opportunities and challenges. Mol Hum Reprod. 2020 Apr 24;26(4):199-214. doi: 10.1093/molehr/gaaa016. — View Citation

Zhang Y, Shi J, Rassoulzadegan M, Tuorto F, Chen Q. Sperm RNA code programmes the metabolic health of offspring. Nat Rev Endocrinol. 2019 Aug;15(8):489-498. doi: 10.1038/s41574-019-0226-2. Epub 2019 Jun 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Semen/Sperm quantity analysis	sperm count and concentration	1 week
Primary	Semen/Sperm quality analysis	semen pH, semen volume, sperm motility, sperm morphology, sperm vitality	1 week
Primary	Fertility classification	Classification into fertile/infertile groups based on the fertility measures.	1 week
Primary	Sperm RNA extraction and sequencing	Sperm RNA extraction and sequencing	3 months
Secondary	Expression profiling of sncRNA	Counts of miRNA, piRNA, tRF from the sequenced data through Bioinformatics analysis. All three sncRNA will be quantified from the RNA sequencing data using bioinformatics tools, with the same unit of measure.	3-6 months
Secondary	Comparison of the expression profiles	Comparison of the expression profiles between the two groups (infertile vs fertile)	3-6 months