We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Autologous Testicular Tissue Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05414045
Recruitment Status : Recruiting
First Posted : June 10, 2022
Last Update Posted : June 10, 2022
Sponsor:
Information provided by (Responsible Party):
Universitair Ziekenhuis Brussel

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs) in case of imminent gonadotoxic treatment during childhood. In case of total azoospermia in adulthood and presence of a childwish, the investigators intend to perform the first in men autologous testicular tissue transplantation to restore fertility.

Condition or disease Intervention/treatment Phase
Cancer Sickle Cell Thalassemia Hematologic Diseases Procedure: Autologous testicular tissue transplantation of prepubertal frozen testicular tissue Not Applicable

Detailed Description:

Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs). In 2002, the University hospital in Brussels (UZB) was the first hospital worldwide to offer testicular tissue cryobanking for fertility preservation in boys and ado-lescents. Since then, several other centers in Europe and USA have implemented similar fertility preservation programs. However, up till now, autologous transplantations of cryopreserved testicular tissue have not been performed yet.

As soon as a patient returns to the Centre for Reproductive Medicine at UZB with the request to transplant the preserved testicular tissue, the investigators will first analyse semen and blood. If spermatozoa are found in their semen, men can immediately enroll in standard care for natural conception, intra-uterine insemination (IUI), in-vitro fertilization (IVF) or intra-cytoplasmic injection (ICSI). However, in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), the investigators intend to propose and eventually perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All eligible patients for the study will have the same treatment: autologous testicular tissue transplantation with testicular tissue containing spermatogonial stemcells frozen at pre-pubertal age. Transplantation will be performed subcutaneously in the scrotum and intra-testicular.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Testicular Tissue Transplantation for Fertility Restoration
Actual Study Start Date : July 29, 2020
Estimated Primary Completion Date : July 29, 2030
Estimated Study Completion Date : October 29, 2030

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Intervention Details:
  • Procedure: Autologous testicular tissue transplantation of prepubertal frozen testicular tissue

    Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs).

    If patient has a childwish on adult age and in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), we will perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Restoration of spermatogenesis and fertility by performing an autologous testicular tissue transplantation. Primary endpoint is the presence of spermatozoa in the graft. [ Time Frame: Graft-removal of intratesticular and intrascrotal grafts is planned 12 months after grafting. ]

    Freezing testicular tissue of prepubertal boys is a method for preserving spermatogonial stem cells (SSCs).

    If patient has a childwish on adult age and in case no spermatozoa are found in the ejaculate or after performing a testicular biopsy (TESE), we will perform autologous testicular tissue transplantation with the primary objective being to restore spermatogenesis and fertility.

    Grafting will be performed intra-testicular and intrascrotal for each patient. Grafts will be removed 12 months after grafting.

    Primary endpoint is the presence of spermatozoa in the grafted tissue.In the IVF laboratory mechanical mincing and enzymatic digestion will be performed on the tissue to find spermatozoa. If spermatozoa are present concentration and motility will be available.



Secondary Outcome Measures :
  1. Histological study to define the optimal transplantation site [ Time Frame: Graft-removal of intratesticular grafts and intrascrotal grafts are planned 12 months after initial grafting. Histological study will be performed 12 months after initial grafting ]
    The presence of sperm-generating stem cells, as well as their possible maturation to sperm cells will be evaluated through available and validated microscopic staining techniques applied to the testicular tissue. The maturity of other, non-sperm-generating testicular cells (Sertoli cells and Leydig cells) will also be evaluated. The results from tissue fragments transplanted to the testicle will be compared to the results from the tissue fragments transplanted to the scrotum. During the removal procedure of the transplanted fragments, a control biopsy (TESE) will be performed on the contra-lateral testicle (the one on which no transplantation was performed).

  2. Imaging study [ Time Frame: Each patient in the study will be followed-up after screening during a period of 12 months post-grafting on 3, 6, 9 and 12 months after initial grafting. ]
    The investigators will study the possibility of analyzing the growth of the transplanted fragments and the development of sperm cell production in these fragments by using ultrasound and Doppler techniques in a non-invasive way. Ultrasound will be performed 3, 6, 9 and 12 months after grafting. These findings will be compared to the findings of the semen and blood analysis and the clinical examination.

  3. Endocrinological (hormonal) study [ Time Frame: Each patient in the study will be followed-up after screening during a period of 12 months post-grafting on 3, 6, 9 and 12 months after initial grafting. ]

    The investigators plan a follow-up of the functionality of the transplanted tissue by performing blood analyses with LH (IU/L), FSH (IU/L), testosterone (ng/L), Inhibine B (ng/L) and Insulin-like factor 3 (INSL3, ng/ml).

    Blood analyses will be repeated 3, 6, 9 and 12 months after the transplantation procedure.


  4. Biomarker Study [ Time Frame: Each patient in the study will be followed-up after screening during a period of 12 months post-grafting on 3, 6, 9 and 12 months after initial grafting. ]
    As an exploratory part of this study, the investigators will study the possibility to predict the presence of testicular spermatogenesis in a non-invasive way (by semen and/or urine samples). If different biomarkers could be identified specificaly for the different stages of spermatogenesis, the development of the transplanted biopsies could be monitored this way. For this study, a urine and semen sample will be needed 3, 6, 9 and 12 months after the transplantation procedure.

  5. Complications [ Time Frame: Each patient in the study will be follow-up after screening during a period of 15 months post-grafting. ]
    Each patient in the study will be followed-up during a period of 15 months after initial grafting or 3 months after graft-removal to report any complication(s) of the procedures.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male infertile survivors of childhood cancer or a hematological disease who underwent prepubertal testicular tissue cryopreservation in case of gonadotoxic treatment.
Accepts Healthy Volunteers:   No
Criteria

The eligible patients opted as a prepubertal boy to enroll in the fertility preservation pro-gram and on the moment of cancer diagnosis or hematological disorder, their parents have agreed to cryopreserve testicular tissue for later autologous transplantation.

Inclusion Criteria:

  • At least 18 years old
  • Desire to become a parent at the moment of intake
  • Stable relationship with a female partner and minimal one year cohabiting
  • Age of female partner < 43 year
  • Azoospermia on 2 semen analyses
  • Normal standardised preliminary and preoperative bloodsampling results
  • Complete remission of the oncological or hematological disease
  • Approval of the treating oncologist or other specialist in case of non-oncological disease as reason for the testicular tissue preservation as a child
  • Risk for presence of malignant cells in testicular tissue is negligible (according to multidisciplinary assessment)
  • Presence of SSCs (positive MAGE staining) in one or two of the thawed fragments (If absence of SSCs in two of the thawed fragments, the case will be discussed multidisciplinary)
  • Written informed consent for the transplantation of cryopreserved testicular tissue and follow-up after the procedure and of children born eventually after this procedure

Exclusion criteria:

  • Risk for presence of malignant cells in the testicular tissue
  • Contra-indication for surgery
  • Contra-indication for pregnancy in the female partner
  • BMI > 32
  • Heavy smoking (≥10 cigarettes/day)
  • Instable psychological condition
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05414045


Contacts
Layout table for location contacts
Contact: Veerle Vloeberghs, MD 003224776699 veerle.vloeberghs@uzbrussel.be
Contact: Herman Tournaye, MD PhD 003224776699 herman.tournaye@uzbrussel.be

Locations
Layout table for location information
Belgium
UZ Brussel Centre for Reproductive Medicine Recruiting
Brussels, Belgium, 1090
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Investigators
Layout table for investigator information
Principal Investigator: Veerle Vloeberghs, MD CRG UZ Brussel
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT05414045    
Other Study ID Numbers: 2019/477
First Posted: June 10, 2022    Key Record Dates
Last Update Posted: June 10, 2022
Last Verified: June 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Thalassemia
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
 Anemia
Hemoglobinopathies
Genetic Diseases, Inborn