NCT04715828

Brief 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. 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
200

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jan 2018

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2018

Completed
3 years until next milestone

First Submitted

Initial submission to the registry

January 15, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 20, 2021

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2022

Completed
Last Updated

January 20, 2021

Status Verified

January 1, 2021

Enrollment Period

4 years

First QC Date

January 15, 2021

Last Update Submit

January 15, 2021

Conditions

Keywords

Fertility PreservationIonizing radiationHuman spermThyroid CancerNuclear alterationsTelomere lengthDNA Fragmentation and OxidationChromatin decondensationConventional sperm parameters

Outcome Measures

Primary Outcomes (1)

  • 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

    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.

    01/01/2018-01/01/2022

  • to measure RAT impact on sperm parameters (vitality, motility and morphology)

    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

    01/01/2018-01/01/2022

  • to evaluate RAT impact on human sperm cells in comparison with cryopreservation

    01/01/2018-01/01/2022

  • to evaluate the impact of different doses and types of irradiation on human sperm cells

    01/01/2018-01/01/2022

  • +1 more secondary outcomes

Study Arms (5)

control arm "fresh"

Fresh semen treated without irradiation before cryopreservation

Other: Cryopreserved semen

control arm "cryopreserved"

cryopreserved semen without irradiation (n=60)

Other: Cryopreserved semen

acute irradiation at low dose

Pelvis scanning : acute irradiation (1 or 2 second) using low dose (n=30),

Other: Acute and low irradiation

long irradiation at low dose

Bone scintigraphy : long irradiation (3h) using low dose (n=30),

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),

Other: Long and medium irradiation

Interventions

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).

control arm "cryopreserved"control arm "fresh"

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

acute irradiation at low dose

sperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours.

long irradiation at low dose

sperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours

long irradiation at medium dose

Eligibility Criteria

Age18 Years - 45 Years
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
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

You may qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU de Clermont-Ferrand

Clermont-Ferrand, 63000, France

RECRUITING

MeSH Terms

Conditions

Thyroid Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsEndocrine System DiseasesThyroid Diseases

Study Officials

  • Hanae PONS-REJRAJI, PhD

    CHU de Clermont-Ferrand

    STUDY CHAIR

Central Study Contacts

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 15, 2021

First Posted

January 20, 2021

Study Start

January 1, 2018

Primary Completion

January 1, 2022

Study Completion

January 1, 2022

Last Updated

January 20, 2021

Record last verified: 2021-01

Locations