Sperm PreservationNCT04715828
Impact of Ionizing Treatment on the Nuclear Structure of Human Spermatozoa.
An observational study of Sperm Preservation and Irradiated Semen, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
Differentiated thyroid cancer is the third cause of cancer in young men of childbearing age. Its treatment by irradiation with Radioactive Iodine 131 therapy (RAT) could alter spermatogenesis and result in azoospermia and permanent infertility. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men only
- Conditions the study is for
- Sperm Preservation, Irradiated Semen
- What is being tested?
- Cryopreserved semen, Acute and low irradiation and Long and low irradiation
- How many people
- 200 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2018to 1 Jan 2022
- 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 45 years
- Men only
- No healthy volunteers
- Adult
Study population: All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent
Who may be able to join
- Man less than 45 years
- Man undergoing routine semen analysis at the Center for Reproductive Medicine, accepting the research protocol and signing the associated consent will be included in the protocol without distinction of physical criteria.
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU de Clermont-Ferrand
Clermont-Ferrand, 63000
Lise Laclautre, PharmD, 04 73 75 49 62 ext. 33, promo_interne_drci@chu-clermontferrand.fr
Hanaé PONS-REJRAJI, PhD
About this study
Differentiated thyroid cancer is the third cause of cancer in young men of childbearing age. Its treatment by irradiation with Radioactive Iodine 131 therapy (RAT) could alter spermatogenesis and result in azoospermia and permanent infertility. A preventive gametes cryopreservation was recommended before RAT, but without mentioning a period of teratogenic risk transmissible to the offspring. To date, RAT impact on human sperm nucleus is poorly known or even unknown, notably on telomere length.
Our objective is to define RAT effects on human sperm nucleus by in vitro irradiation exposure of human spermatozoa to mimicking that of the gonads in the context of irradiation with iodine131 used for thyroid cancer. We will analyze standard sperm parameters, major DNA alterations and telomere length using molecular and cellular assays. Nucleus morphology and chromatin organization will also be analyzed using 3D bio-imaging. This study will permit to optimize the indications for the preservation of fertility.
Read the detailed description
Our main objective is to measure the in vitro impact of irradiation treatment on sperm nuclear quality such as DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and notably sperm telomere length (STL).
The secondary objectives are :
- to measure RAT impact on sperm parameters (vitality, motility and morphology)
- to measure the impact of cryopreservation on chromatin organisation and nucleus morphology
- to evaluate RAT impact on human sperm cells in comparison with cryopreservation
- to evaluate the impact of different doses and types of irradiation on human sperm cells
- to establish relations between potential alterations of standards sperm parameters (vitality, motility and morphology) and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL.
Our final goal is to provide a significant improvement of men fertility diagnosis and optimize our fertility preservation practices.
To this end, we will expose ejaculated human spermatozoa (n = 90) at different (low and moderate) doses of gamma or X photons to mimic gonads irradiation. Absorbed doses by the samples were calculated using the GATE Monte Carlo platform (version 8.2). Experiment geometry settings were modelled as three dimension voxelized volumes inside the software by assigning a shape, size, distance and density for all the volumes created. All measurements will be made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples are collected and subdivided into 3 arms to analyse sperm quality after:
- irradiation exposure (3 conditions);
- a freezing- thawing cycle;
- fresh state: negative control without treatment.
Before (fresh state) and after each treatment we will analyse:
- standard semen parameters (vitality, motility and morphology) in accordance with WHO, 2010;
- STL using Flow FISH, q-PCR and q-FISH;
- chromatin condensation (chromomycin A3);
- DNA oxidization (8-OHdG residues);
- DNA fragmentation (TUNEL);
- 3D nucleus structure using 3D bio-imaging.
- Conditions
- Sperm Preservation, Irradiated Semen
- Being tested
- Cryopreserved semen, Acute and low irradiation, Long and low irradiation, Long and medium irradiation
- Keywords
- Fertility Preservation, Ionizing radiation, Human sperm, Thyroid Cancer, Nuclear alterations, Telomere length, DNA Fragmentation and Oxidation, Chromatin decondensation, Conventional sperm parameters
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryopreserved semenOther
sperm will be frozen in Cryosperm® cryoprotectant medium (Origio). The samples will be packaged in previously identified high security straws (Cryobiosystem). Slow freezing of the straws will be carried out using the Nanodigicool® programmable device (Cryobiosystem).
Acute and low irradiationOther
sperm sample will be placed on the scanner's processing table to be exposed for 1 to 2 seconds. Several dose levels will then be made in order to limit the value of 17 mGy
Long and low irradiationOther
sperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours.
Long and medium irradiationOther
sperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours
| Study group | Role | What they receive |
|---|---|---|
| control arm "fresh" | Fresh semen treated without irradiation before cryopreservation Receives: Other: Cryopreserved semen | |
| control arm "cryopreserved" | cryopreserved semen without irradiation (n=60) Receives: Other: Cryopreserved semen | |
| acute irradiation at low dose | Pelvis scanning : acute irradiation (1 or 2 second) using low dose (n=30), Receives: Other: Acute and low irradiation | |
| long irradiation at low dose | Bone scintigraphy : long irradiation (3h) using low dose (n=30), Receives: Other: Long and low irradiation | |
| long irradiation at medium dose | Radioactive Iodine 131 therapy (RAT) applied for thyroid cancer : long irradiation (3h) using medium dose (n=60), Receives: Other: Long and medium irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure in vitro the impact of an ionizing radiation treatment on sperm nuclear quality and in particular the size of telomeres.
To achieve this goal, we will expose human sperm to an irradiation dose of I131 to mimic the irradiation of gonads and sperm. Reliquat of semen will be cryopreserved (control condition). After thawing, the same sample will be subdivised into 2 groups in order to analyze the sperm quality :
- After an irradiation dose of I131
- After a cryopreservation
Measured: 01/01/2018-01/01/2022
Secondary outcomes (6)
To measure in vitro the impact of an irradiation dose of I131 on sperm nuclear quality, notably on STL.
All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be collected and subdivided into 3 arms to analyse sperm quality after:
- irradiation exposure (3 conditions);
- a freezing- thawing cycle;
- fresh state: negative control without treatment.
Before (fresh state) and after each treatment we will analyse:
- STL using Flow FISH, q-PCR and q-FISH;
- chromatin condensation (chromomycin A3);
- DNA oxidization (8-OHdG residues);
- DNA fragmentation (TUNEL);
- 3D nucleus structure using 3D bio-imaging.
Measured: 01/01/2018-01/01/2022
to measure RAT impact on sperm parameters (vitality, motility and morphology)
All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be collected and subdivided into 3 arms to analyse sperm quality after:
- irradiation exposure (3 conditions);
- a freezing- thawing cycle;
- fresh state: negative control without treatment.
- a freezing- thawing cycle;
- fresh state: negative control without treatment. Before (fresh state) and after each treatment we will analyse standard semen parameters (vitality, motility and morphology) in accordance with WHO, 2010;
Measured: 01/01/2018-01/01/2022
To measure in vitro the impact of cryopreservation on sperm nuclear quality, notably on STL, chromatin organisation and nucleus morphology
All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be collected and subdivided into 3 arms to analyse sperm quality after:
- irradiation exposure (3 conditions);
- a freezing- thawing cycle;
- fresh state: negative control without treatment.
Before (fresh state) and after each treatment we will analyse:
- STL using Flow FISH, q-PCR and q-FISH;
- chromatin condensation (chromomycin A3);
- DNA oxidization (8-OHdG residues);
- DNA fragmentation (TUNEL);
- 3D nucleus structure using 3D bio-imaging.
Measured: 01/01/2018-01/01/2022
to evaluate RAT impact on human sperm cells in comparison with cryopreservation
We will compare effects induced by RAT and cryopreservation on each sperm sample. In order to limit the bias, for each irradiation treatment, a sample of sperm cells (cryopreserved control) will be treated under identical conditions.
Measured: 01/01/2018-01/01/2022
to evaluate the impact of different doses and types of irradiation on human sperm cells
All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples will be collected and subdivided into 3 arms to analyse sperm quality after:
- irradiation exposure (3 conditions);
- a freezing- thawing cycle;
- fresh state: negative control without treatment.
Irradiation exposure will be realised under 3 conditions:
- acute and low irradiation : sperm sample will be placed on the scanner's processing table to be exposed for 1 to 2 seconds. Several dose levels will then be made in order to limit the value of 17 mGy.
- long and low irradiation: sperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours.
- long and medium irradiation : sperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours
Measured: 01/01/2018-01/01/2022
to establish relations between potential alterations of standards sperm parameters (vitality, motility and morphology) and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL.
We will correlate the effects induced by on vitality, motility and morphology and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL.
Measured: 01/01/2018-01/01/2022
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2021
- Study start1 Jan 2018
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sperm PreservationStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe 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
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Collaborators
- Agence de La Biomédecine
- Responsible party
- Sponsor
- Investigators
- Hanae PONS-REJRAJI, PhD, Study chair, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04715828
- Sponsor's protocol ID
- 2020 PONS-REJRAJI
- Status last verified
- Jan 2021
- First submitted
- 15 Jan 2021
- Last updated
- 20 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Ionizing Treatment on the Nuclear Structure of Human Spermatozoa.
- ClinicalTrials.gov ID
- NCT04715828
- Acronym / sponsor ID
- 2020 PONS-REJRAJI
- Conditions
- Sperm Preservation, Irradiated Semen
- Keywords
- Fertility Preservation, Ionizing radiation, Human sperm, Thyroid Cancer, Nuclear alterations, Telomere length, DNA Fragmentation and Oxidation, Chromatin decondensation
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Collaborators
- Agence de La Biomédecine
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 20 Jan 2021 (actual)
- 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.
Differentiated thyroid cancer is the third cause of cancer in young men of childbearing age. Its treatment by irradiation with Radioactive Iodine 131 therapy (RAT) could alter spermatogenesis and result in azoospermia and permanent infertility. A preventive gametes cryopreservation was recommended before RAT, but without mentioning a period of teratogenic risk transmissible to the offspring. To date, RAT impact on human sperm nucleus is poorly known or even unknown, notably on telomere length.
Our objective is to define RAT effects on human sperm nucleus by in vitro irradiation exposure of human spermatozoa to mimicking that of the gonads in the context of irradiation with iodine131 used for thyroid cancer. We will analyze standard sperm parameters, major DNA alterations and telomere length using molecular and cellular assays. Nucleus morphology and chromatin organization will also be analyzed using 3D bio-imaging. This study will permit to optimize the indications for the preservation of fertility.
Detailed description
Our main objective is to measure the in vitro impact of irradiation treatment on sperm nuclear quality such as DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and notably sperm telomere length (STL).
The secondary objectives are :
- to measure RAT impact on sperm parameters (vitality, motility and morphology)
- to measure the impact of cryopreservation on chromatin organisation and nucleus morphology
- to evaluate RAT impact on human sperm cells in comparison with cryopreservation
- to evaluate the impact of different doses and types of irradiation on human sperm cells
- to establish relations between potential alterations of standards sperm parameters (vitality, motility and morphology) and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL.
Our final goal is to provide a significant improvement of men fertility diagnosis and optimize our fertility preservation practices.
To this end, we will expose ejaculated human spermatozoa (n = 90) at different (low and moderate) doses of gamma or X photons to mimic gonads irradiation. Absorbed doses by the samples were calculated using the GATE Monte Carlo platform (version 8.2). Experiment geometry settings were modelled as three dimension voxelized volumes inside the software by assigning a shape, size, distance and density for all the volumes created. All measurements will be made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples are collected and subdivided into 3 arms to analyse sperm quality after:
- irradiation exposure (3 conditions);
- a freezing- thawing cycle;
- fresh state: negative control without treatment.
Before (fresh state) and after each treatment we will analyse:
- standard semen parameters (vitality, motility and morphology) in accordance with WHO, 2010;
- STL using Flow FISH, q-PCR and q-FISH;
- chromatin condensation (chromomycin A3);
- DNA oxidization (8-OHdG residues);
- DNA fragmentation (TUNEL);
- 3D nucleus structure using 3D bio-imaging.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| control arm "fresh" | – | Other: Cryopreserved semenFresh semen treated without irradiation before cryopreservation |
| control arm "cryopreserved" | – | Other: Cryopreserved semencryopreserved semen without irradiation (n=60) |
| acute irradiation at low dose | – | Other: Acute and low irradiationPelvis scanning : acute irradiation (1 or 2 second) using low dose (n=30), |
| long irradiation at low dose | – | Other: Long and low irradiationBone scintigraphy : long irradiation (3h) using low dose (n=30), |
| long irradiation at medium dose | – | Other: Long and medium irradiationRadioactive Iodine 131 therapy (RAT) applied for thyroid cancer : long irradiation (3h) using medium dose (n=60), |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- All measurements are made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent
Key inclusion criteria (2 listed)
- Man less than 45 years
- Man undergoing routine semen analysis at the Center for Reproductive Medicine, accepting the research protocol and signing the associated consent will be included in the protocol without distinction of physical criteria.
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cryopreserved semensperm will be frozen in Cryosperm® cryoprotectant medium (Origio). The samples will be packaged in previously identified high security straws (Cryobiosystem). Slow freezing of the straws will be carried out using the Nanodigicool® programmable device (Cryobiosystem). | Other | control arm "cryopreserved", control arm "fresh" |
| Acute and low irradiationsperm sample will be placed on the scanner's processing table to be exposed for 1 to 2 seconds. Several dose levels will then be made in order to limit the value of 17 mGy | Other | acute irradiation at low dose |
| Long and low irradiationsperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours. | Other | long irradiation at low dose |
| Long and medium irradiationsperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours | Other | long irradiation at medium dose |
Primary outcome
To measure in vitro the impact of an ionizing radiation treatment on sperm nuclear quality and in particular the size of telomeres.
Time frame: 01/01/2018-01/01/2022
To achieve this goal, we will expose human sperm to an irradiation dose of I131 to mimic the irradiation of gonads and sperm. Reliquat of semen will be cryopreserved (control condition). After thawing, the same sample will be subdivised into 2 groups in order to analyze the sperm quality : * After an irradiation dose of I131 * After a cryopreservation
6 secondary outcomes
To measure in vitro the impact of an irradiation dose of I131 on sperm nuclear quality, notably on STL.
Time frame: 01/01/2018-01/01/2022
to measure RAT impact on sperm parameters (vitality, motility and morphology)
Time frame: 01/01/2018-01/01/2022
To measure in vitro the impact of cryopreservation on sperm nuclear quality, notably on STL, chromatin organisation and nucleus morphology
Time frame: 01/01/2018-01/01/2022
to evaluate RAT impact on human sperm cells in comparison with cryopreservation
Time frame: 01/01/2018-01/01/2022
to evaluate the impact of different doses and types of irradiation on human sperm cells
Time frame: 01/01/2018-01/01/2022
to establish relations between potential alterations of standards sperm parameters (vitality, motility and morphology) and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL.
Time frame: 01/01/2018-01/01/2022
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- Individual participant dataSharing planned: Undecided
Related trials for Sperm Preservation
Not yet recruitingObservational study
Outcomes for Patients Who Preserved Their Fertility as Part of Cancer Treatment at the Center for the Study and Preservation of Eggs and Sperm: MaPreservFerti
Fertility, Male Cancer
Not yet recruitingPhase 2
Can Fat-Burning Shots Boost Fertility? Comparing Weight-Loss Injections vs. Healthy Habits for Obese Men With Low Sperm Health
Obesity-related Male Infertility
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.
Hanae PONS-REJRAJI, PhD study chair
University Hospital, Clermont-Ferrand
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 Sperm Preservation and Irradiated Semen, run by University Hospital, Clermont-Ferrand at 1 site in France.
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 2 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: status not confirmed, as of the sponsor's last update on 20 Jan 2021. 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 France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lise Laclautre, PharmD (04 73 75 49 63 ext. 34, promo_interne_drci@chu-clermontferrand.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure in vitro the impact of an ionizing radiation treatment on sperm nuclear quality and in particular the size of telomeres. (time frame: 01/01/2018-01/01/2022). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Jan 2021.