Personalized Signature of Chronic Inflammation and Early Aging Predictive of the Comorbidities in Infertile Men

NCT ID: NCT06082362

Last Updated: 2023-10-13

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 350 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-06-21
• Study Completion Date: 2025-06-20

Brief Summary

The aim of the project is identify new biomarkers and/or prognostic factors in order to develop personalized strategies to prevent the onset of tumor and/or non tumor comorbidity in infertile men.

Detailed Description

Infertility is a disease of nearly endemic proportions, affecting up to 15% of couples of reproductive ages. Overall, a pure male factor infertility underlies the problem in at least 30% of cases. General health status in infertile men is gaining increasing clinical attention throughout the last decades. Indeed, infertile men were shown to be at increased risk of nononcologic and oncologic morbidity and mortality compared to age-comparable fertile ones. Despite emerging and solid epidemiological studies, the common ground fostering overall health status and male infertility is still far from being understood. Notwithstanding the numerous hypotheses that have been considered to explain the potential link overall men's health status and male infertility - e.g., including genetic, endocrinological, and metabolic abnormalities - the exact nature of these associations remains unclear. Recent clinical findings showed evidence of onset of age-related comorbidities 10-15 years earlier in infertile compared to fertile men. Single-cell transcriptome profiling of testes of men with idiopathic germ cell aplasia revealed an immature testis with a somatic environment stuck at puberty with immaturity of Leydig cells associated with chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. Compelling evidence indicate that defects in the regulatory arms of the immune system and metabolic status can be associated with the risk of developing numerous oncological and non-oncological diseases. Thus far, limited reliable data on the immunological status of infertile men are available. Preliminary data from the coordinating group of the project revealed increased pro-inflammatory cells and reduced T cells in peripheral blood of infertile men. Moreover, the few T cells observed in infertile men displayed an exhausted phenotype. The investigators proposed an innovative multidisciplinary approach to identify causal links between infertility as a disease and chronic inflammation and comorbidities. Moreover, the investigators aim at identifying novel prognostic biomarkers/tools toward the development of tailored prevention strategies of severe comorbidities in infertile men. They will combine extensive clinical data of a unique and homogenous cohort of infertile men and controls with state-of-the art transcriptomic approaches, a comprehensive monitoring and functional characterization of adaptive and innate immune cells, and the endocrine-metabolomic signature of men with primary infertility. The success of our strategy will be instrumental for defining novel molecular causes of male infertility, along with the pathophysiological mechanism behind the higher burden of comorbid conditions. Results will provide information on cell compartments, and the senescent and endocrine status, mostly in men with primary idiopathic infertility, and new insights into the etiology responsible for the early onset of comorbidities in infertile men. This will represent a breakthrough in the infertility field and a major advancement towards better caring of male patients and healthy ageing in the real-life setting and will set the stage for the development of more tailored clinical approaches to prevent malignant and nonmalignant comorbidities in infertile men. Thereof, the findings of the research project will have a significant rebound in terms of cost-effectiveness on the national health system.

Conditions

Male Infertility

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Infertile men

Men with infertility

Collection of clinical and biological material

Intervention Type: OTHER

Collection of clinical and biological material (e.g., samples of semen, stool, urine, blood, buccal swab)

Fertile men

Fertile men

Collection of clinical and biological material

Intervention Type: OTHER

Collection of clinical and biological material (e.g., samples of semen, stool, urine, blood, buccal swab)

Oncologic patients

Patients with kidney, bladder, chest, or pancreas tumors

Collection of clinical and biological material

Intervention Type: OTHER

Collection of clinical and biological material (e.g., samples of semen, stool, urine, blood, buccal swab)

Interventions

Collection of clinical and biological material

Collection of clinical and biological material (e.g., samples of semen, stool, urine, blood, buccal swab)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age > 18 and < 50 years;
• White race
• Men with OAT o iNOA infertility diagnosis
• ability to sign the consent information

Exclusion Criteria

• inability to sign the consent information
• secondary infertility diagnosis
• history of hematological diseases
• people treated with antibiotics in the six months prior the enrollment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Andrea Salonia

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea Salonia, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale San Raffaele

Locations

IRCCS Ospedale San Raffaele

Milan, Lombardy, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Andrea Salonia, MD

Role: CONTACT

salonia.andrea@hsr.it

02 2643 5661

Alessia d'Arma, MSc

Role: CONTACT

darma.alessia@hsr.it

02 2643 5506

Facility Contacts

Alessia d'Arma, MSc

Role: primary

darma.alessia@hsr.it

02 2643 5506

Other Identifiers

PNRR-MAD-2022-12375994

Identifier Type: -

Identifier Source: org_study_id