Male InfertilityNCT02756923
Regulation of Stem Spermatogonia in the Mature Testis
An observational study of Male Infertility, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Investigative trial to evaluate the role of a glial cell lined derived neurotrophic factor (GDNF) in regulation of spermatogonial renewal and testicular function. Goal of the trial is to provide greater information on the mechanisms that effect stem spermatogonial maintenance renewal and proliferation in its relation… Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Male Infertility
- How many people
- 142 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to 5 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Healthy males undergoing testicular biopsy by any urologic surgeon at Weill Cornell Medicine.
Who may be able to join
- undergoing testicular biopsy at Weill Cornell Medicine/New York Presbyterian
Who cannot join
- females and any males outside of the age parameter of 18-75 years old
Trial locations and contacts
1 site in 1 country.
About this study
Investigative trial to evaluate the role of a glial cell lined derived neurotrophic factor (GDNF) in regulation of spermatogonial renewal and testicular function. Goal of the trial is to provide greater information on the mechanisms that effect stem spermatogonial maintenance renewal and proliferation in its relation to male infertility.
Read the detailed description
An essential requirement for sustaining male fertility is maintaining an adequate number of stem spermatogonia, the foundation of spermatogenesis. To achieve this, when the stem cells divide, some progeny must remain stem spermatogonia while other progeny differentiate. It is obvious that the correct balance between self-renewing replication and differentiation of stem spermatogonia is crucial to male fertility, and there is a indirect evidence that GDNF plays an important role in maintaining this balance in the normal mature testis. However, almost nothing is known about the in vivo regulation of this balance in the mature organ, of the specific function of GDNF in the adult testis, or if physiological changes in GDNF expression significantly affect the replication or differentiation of the stem cells. To address these critical issues, a unique mouse model that allows GDNF signaling to the stem spermatogonia to be specifically and reversibly inhibited in vivo by an ATP antagonist. With this model, the first direct evidence that GDNF is required for maintaining the stem spermatogonial pool in a normal mature testis. Additionally, the investigators have shown that when inhibition of GDNF signaling is reversed, the stem cells begin to rebuild the stem cell pool. Importantly, our data demonstrate that some stem spermatogonia are lost when GDNF signaling is inhibited for as little as 2 days, while other stem cells survive for up to 11 days. This suggests that factors intrinsic or extrinsic to the stem cells modulate the response to GDNF. Using this new mouse model the mechanisms responsible for the loss of stem spermatogonia proliferation and regeneration will be investigated along with GDNF signaling and inhibition. At the end of all of this these studies will be done on waste tissue obtained from normal men and men with infertility who otherwise have testicular surgery for therapeutic purposes.
- Conditions
- Male Infertility
- Keywords
- Male Infertility, Spermatogonial stem cell
- Medical subject headings
- Infertility, Male
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue obtained from infertile patients
Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue.
Measured: five years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2016 (estimated)
- Study startApr 2012
- Primary completion7 Nov 2019
- Study completion5 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Male InfertilityStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Peter N Schlegel, M.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02756923
- Sponsor's protocol ID
- 1202012193
- Other IDs
- 1P50HD096723-01A1
- Status last verified
- Mar 2023
- First submitted
- 13 Apr 2016
- Last updated
- 24 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Singh D, Paduch DA, Schlegel PN, Orwig KE, Mielnik A, Bolyakov A, Wright WW. The production of glial cell line-derived neurotrophic factor by human sertoli cells is substantially reduced in sertoli cell-only testes. Hum Reprod. 2017 May 1;32(5):1108-1117. doi: 10.1093/humrep/dex061.
PubMed 28369535Paduch DA, Hilz S, Grimson A, Schlegel PN, Jedlicka AE, Wright WW. Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome. PLoS One. 2019 May 9;14(5):e0216586. doi: 10.1371/journal.pone.0216586. eCollection 2019.
PubMed 31071133
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Stem Spermatogonia in the Mature Testis
- ClinicalTrials.gov ID
- NCT02756923
- Acronym / sponsor ID
- 1202012193
- Conditions
- Male Infertility
- Keywords
- Male Infertility, Spermatogonial stem cell
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Apr 2012
- Primary completion
- 7 Nov 2019 (actual)
- Study completion
- 5 Dec 2019 (actual)
- First posted
- 29 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigative trial to evaluate the role of a glial cell lined derived neurotrophic factor (GDNF) in regulation of spermatogonial renewal and testicular function. Goal of the trial is to provide greater information on the mechanisms that effect stem spermatogonial maintenance renewal and proliferation in its relation to male infertility.
Detailed description
An essential requirement for sustaining male fertility is maintaining an adequate number of stem spermatogonia, the foundation of spermatogenesis. To achieve this, when the stem cells divide, some progeny must remain stem spermatogonia while other progeny differentiate. It is obvious that the correct balance between self-renewing replication and differentiation of stem spermatogonia is crucial to male fertility, and there is a indirect evidence that GDNF plays an important role in maintaining this balance in the normal mature testis. However, almost nothing is known about the in vivo regulation of this balance in the mature organ, of the specific function of GDNF in the adult testis, or if physiological changes in GDNF expression significantly affect the replication or differentiation of the stem cells. To address these critical issues, a unique mouse model that allows GDNF signaling to the stem spermatogonia to be specifically and reversibly inhibited in vivo by an ATP antagonist. With this model, the first direct evidence that GDNF is required for maintaining the stem spermatogonial pool in a normal mature testis. Additionally, the investigators have shown that when inhibition of GDNF signaling is reversed, the stem cells begin to rebuild the stem cell pool. Importantly, our data demonstrate that some stem spermatogonia are lost when GDNF signaling is inhibited for as little as 2 days, while other stem cells survive for up to 11 days. This suggests that factors intrinsic or extrinsic to the stem cells modulate the response to GDNF. Using this new mouse model the mechanisms responsible for the loss of stem spermatogonia proliferation and regeneration will be investigated along with GDNF signaling and inhibition. At the end of all of this these studies will be done on waste tissue obtained from normal men and men with infertility who otherwise have testicular surgery for therapeutic purposes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy males undergoing testicular biopsy by any urologic surgeon at Weill Cornell Medicine.
Key inclusion criteria (1 listed)
- undergoing testicular biopsy at Weill Cornell Medicine/New York Presbyterian
Key exclusion criteria (1 listed)
- females and any males outside of the age parameter of 18-75 years old
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue obtained from infertile patients
Time frame: five years
Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
- Results publication: PubMed 28369535Singh D, Paduch DA, Schlegel PN, Orwig KE, Mielnik A, Bolyakov A, Wright WW. The production of glial cell line-derived neurotrophic factor by human sertoli cells is substantially reduced in sertoli cell-only testes. Hum Reprod. 2017 May 1;32(5):1108-1117. doi: 10.1093/humrep/dex061.
- Results publication: PubMed 31071133Paduch DA, Hilz S, Grimson A, Schlegel PN, Jedlicka AE, Wright WW. Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome. PLoS One. 2019 May 9;14(5):e0216586. doi: 10.1371/journal.pone.0216586. eCollection 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter N Schlegel, M.D. principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Male Infertility, run by Weill Medical College of Cornell University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of glial cell line derived neurotrophic factor (GDNF) in normal testis compared to abnormal testicular tissue obtained from infertile patients (time frame: five years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02756923, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.