NCT06584994

Brief Summary

Gametogenesis is the production of sperm and eggs; it takes place through the process of meiosis. Gametogenesis is subject to the acquisition of mutations as with other processes in the body. Many of these mutations are somatic, meaning that they occur during life as part of the process of cell division rather than being passed down from parents. When somatic mutations take place during gametogenesis, there is the potential for hereditary genetic consequences. However, the processes that cause the mutations during gametogenesis and the implications they have for heritability and disease predisposition are poorly understood. The goal of this research is to provide a detailed description of the genetic changes in gonadal tissues, and to understand how mutations acquired during the production of germ cells (sperm and eggs) contribute to the predisposition to a wide range of rare diseases and cancer predisposition in future offspring.

Trial Health

75
On Track

Trial Health Score

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

Enrollment
1,000

participants targeted

Target at P75+ for all trials

Timeline
8mo left

Started Jun 2021

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
enrolling by invitation

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress88%
Jun 2021Mar 2027

Study Start

First participant enrolled

June 20, 2021

Completed
3 years until next milestone

First Submitted

Initial submission to the registry

July 4, 2024

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 5, 2024

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

September 5, 2024

Status Verified

July 1, 2024

Enrollment Period

5.7 years

First QC Date

July 4, 2024

Last Update Submit

September 2, 2024

Conditions

Predisposition, GeneticCancerMutationFertility Disorders

Outcome Measures

Primary Outcomes (1)

  • How often mutations accumulate in healthy reproductive tissues

    Establish how often mutations (changes in DNA) accumulate in healthy reproductive tissues (testes and ovaries).

    7 years

Secondary Outcomes (3)

  • Identification and Characterisation of Mutations

    7 years

  • Comparative Analysis of Mutation Rates

    7 years

  • Inheritance and Transmission Risk

    7 years

Study Arms (3)

Individuals and Families affected by disease predisposition syndromes

We will work with collaborators to identify cohorts of families in which one or more members suffer with a cancer predisposition syndromes such as LFS. The affected individual/s act as an index participant and their unaffected family members act as controls. This may include immediate family (father, mother and affected/non-affected siblings) and extended family members (grandparents, maternal/paternal uncles and aunts) where practical. We wish to collect blood samples, buccal swabs, skin swabs, saliva and/ or urine samples. Adult males (affected and unaffected) may (cohort dependant) also be asked to collect a semen sample for use in the study. We will ask affected individuals if we can access any leftover tumour biopsies and/or material from medical procedures for use in the study.Material will only be accessed once it is not required for diagnostic purposes.

Other: sample collection

Individuals attending fertility clinics with or without fertility problems

For males who are attending fertility clinics we will require blood or saliva samples along with a semen sample as a minimum to take part in this arm of the study.

Other: sample collection

Individuals receiving treatment for cancers in the reproductive system

These participants will have to agree to donate a blood sample (and a semen sample for adult male participants) both before and after their treatment. If any participants do not wish to give a blood sample, we may be able to collect a saliva sample or buccal swab instead.

Other: sample collection

Interventions

sample collectionOTHER

Collection of blood, skin, semen, urine and/or saliva samples. Access to previously collected tissue samples (if applicable).

Individuals and Families affected by disease predisposition syndromesIndividuals attending fertility clinics with or without fertility problemsIndividuals receiving treatment for cancers in the reproductive system

Eligibility Criteria

Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Children diagnosed with disease predisposition syndromes and/or cancer and their family members (mother, father, siblings) We may also include the wider family (maternal/paternal aunts, uncles and grandparents) Recruitment and the sequencing of both prospectively collected samples and those retrospectively collected from tissue banks will run for the first four years of the study.

You may qualify if:

  • Minimum of child affected with cancer pre-disposition syndromes and their father
  • Additional family members of consented father and child duos (Mother, same parent siblings, Maternal/Paternal Aunts, uncles and grandparents of affected child)
  • Reproductive tissue samples from both men and women affected by cancer collected with consent for use in research.
  • Reproductive tissue samples from both men and women unaffected by cancer collected with consent for use in research.

You may not qualify if:

  • Fathers who do not wish to donate a semen sample or are unable to will be excluded from the study, as will their families
  • Fathers who have had a vasectomy will be excluded from the study as will their families
  • Adults who do not have the capacity to consent for themselves will be excluded from the study.
  • Families in which both parents do not have capacity to consent will also be excluded as they will be unable to give parental consent for their children's participation.
  • In order to be eligible siblings must share the same two parents as the affected child, all other siblings will be excluded from the study.
  • Male relatives in the extended family (Maternal/Paternal Aunts, uncles and grandparents of affected child) unwilling or unable to donate both a blood or saliva sample and a semen sample will be excluded from the study.
  • Participants who do not have a good understanding of the English language will be excluded from the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Wellcome Sanger Institute

Cambridge, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Extracted DNA, tumour, blood, saliva, buccal samples, skin, semen and human tissue will be stored at Sanger for the duration of the study.

MeSH Terms

Conditions

Genetic Predisposition to DiseaseNeoplasms

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Disease SusceptibilityDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative Techniques

Study Officials

  • Raheleh Rahbari

    Wellcome Sanger Institute

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

July 4, 2024

First Posted

September 5, 2024

Study Start

June 20, 2021

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Last Updated

September 5, 2024

Record last verified: 2024-07

Locations

GB(1)