Clinical trial NCT06841861: Spermatogonial Differentiation Via Testicular Organoid
Official title: A Study of Therapeutic Spermatogonial Differentiation for Infertile Men Via Testicular Organoid
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Infertility, Male
Gene Abnormality
Sterility, Male
Lead sponsor: CellARTs Inc.
Sponsor class: INDUSTRY
Collaborators: name: The Turek Clinic, Inc
First posted: 2025-02-24
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All participants will be donating human tissue serum (blood), skin (via biopsy), and testicular tissue (via biopsy). These samples will be used for:

1. Primary cell culture of tissue cells will be established and genetic reprogramming could be applied to induce the long-term propagation of living cells.
2. Characterization and genetic screening of cells will be done to discover and reveal known or novel infertility-related biomarkers or genes.
3. Genetic reprogramming. Certain genes or gene products are inserted into donated cells to study how the cells can be changed, or reprogrammed, into embryonic-like cells or into sperm precursor cells.
4. Culture of cells in testicular organoids. Genetically unmodified or modified cells from donated samples could be placed in a laboratory-based testicular environment to see if sperm can be made.
Primary purpose: OTHER

Brief summary: Purpose:

This clinical trial aims to explore the potential for human sperm production in vitro by sustaining a laboratory-cultured adult testicular environment. It also seeks to identify genetic factors contributing to human sterility and failed spermatogenesis. The study's primary objectives include:

1. Identifying genomic markers associated with sterility and failed spermatogenesis.
2. Developing an ex vivo (outside the body) testis "organ-on-a-chip" ("iTestis") to support stem cell cultivation.
3. Determining whether human spermatogenesis can be re-created in vitro using stem cells nurtured in the iTestis model.

Study Description:

Researchers will analyze the genomic profiles of fertile and sterile male participants to map genetic abnormalities associated with sterility. Using testicular and skin tissue samples from participants, spermatogonial stem cells and pluripotent stem cells will be isolated and utilized to construct the ex vivo iTestis. This system will integrate genomic insights and prior research to foster human spermatogenesis outside the body.

Participant Involvement:

Participants will provide the following samples:

* Blood sample for serum analysis.
* A skin tissue biopsy.
* Testicular tissue, obtained through fine needle aspiration (FNA) or testicular sperm extraction (TESE), as part of a routine procedure.

All procedures will be conducted by the principal investigator and qualified research staff, ensuring participant safety and adherence to ethical guidelines.


Eligibility criteria: Inclusion Criteria: Group 1 (Fertile Control)

* Male sex of reproductive age (between 18 - 60 years old).
* Evidence of fertility or normal spermatogenesis.
* Will undergo study procedures in conjunction with their planned fertility or infertility procedures performed for clinical purposes.

Inclusion Criteria: Group 2 and 3 (Infertile)

* Male sex of reproductive age (between 18 - 60 years old).
* Males with evidence of \>1 year of infertility.
* Posesses diagnosis of azoospermia is on clinical evaluation.
* Will undergo study procedures in conjunction with their planned fertility or infertility procedures performed for clinical purposes.

Exclusion Criteria:

- The lack of diagnosis of fertility or infertility, and lack of testicles.

Primary outcomes:
measure: Successful derivation of patient-specific human spermatogonial stem cells (hSSCs) from testicular tissue samples.
timeFrame: From initial sample collection to 24 months post all subject sample collection completion
Secondary outcomes:
Other outcomes:
measure: Development and functional validation of an ex vivo testis organ-on-a-chip ('iTestis') platform for the cultivation and maintenance of isolated spermatogonial stem cells (hSSCs)
timeFrame: From the date of the first successful derivation of patient-specific hSSCs until an ex vivo testis platform is developed and can functionally cultivate and maintain the isolated spermatogonial stem cells (hSSCs), assessed for up to 24 months.
measure: Promotion of human spermatogenesis in vitro ('iSperm') using hSSCs and hiPSCs within the iTestis platform.
timeFrame: From the date of the initial development of the ex vivo testis platform until the promotion of human spermatogenesis using hSSCs and hiPSCs is achieved within the iTestis platform, assessed for up to 24 months.
measure: Successful derivation of patient-specific induced pluripotent stem cells (hiPSCs) from skin samples.
timeFrame: From initial sample collection to 24 months post all subject sample collection completion.
Locations:
city: San Francisco
country: United States
facility: The Turek Clinic
state: California
Study officials:
affiliation: Chief Medical Officer
name: Paul J Turek, MD
role: PRINCIPAL_INVESTIGATOR
References:
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