Paternally Inherited Phenotypes in Cholestasis
PIP-C
Investigation of the Effect of Raised Serum Bile Acids on the Epigenome of Sperm and the Association With the Metabolic Health of the Children of Men With Cholestasis: a Case-control Study.
1 other identifier
observational
200
1 country
2
Brief Summary
For some years investigators have known that the health of fathers at the time their baby is conceived has an influence on the health of their child in the future. Many studies looking at this effect have investigated fathers with obesity and other metabolic disorders. These disorders can alter the risk of obesity and diabetes in the children of these men. More recently, studies have been undertaken to establish the mechanism by which this risk is inherited by the children. Studies of sperm have identified that changes in the structure and function of the sperm play a role. Primary Sclerosing Cholangitis (PSC) and Primary Biliary Cholangitis (PBC) are included in a group of cholestatic liver disorders that are associated with elevated levels of bile acids in the blood (cholestasis). A previous study has established that children born to women who have cholestasis during pregnancy are at an increased risk of obesity later in life. Our study will investigate whether there is a similar effect on the health of children if their father has cholestasis. The study has 2 arms, the Sperm Epigenome arm and the Outcomes arm. In the Sperm Epigenome arm of the study, the structure and function of sperm from men with PSC, PBC and other cholestatic liver disorders will be investigated and compared to the structure and function of sperm from healthy men. In the Outcomes arm of the study, basic health parameters of fathers who had PSC, PBC or another cholestatic liver disease either before or after their child was conceived will be studied. Basic health parameters will also be studied in their child when the child is between 16 and 25 years of age.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Feb 2017
Typical duration for all trials
2 active sites
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
February 8, 2017
CompletedFirst Submitted
Initial submission to the registry
November 1, 2017
CompletedFirst Posted
Study publicly available on registry
November 8, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2020
CompletedAugust 2, 2019
July 1, 2019
3.2 years
November 1, 2017
August 1, 2019
Conditions
Outcome Measures
Primary Outcomes (5)
Impact of male cholestasis on DNA methylation patterns in sperm
01/04/2018
Impact of male cholestasis on small RNA content in sperm
01/04/2018
Impact of male cholestasis on sperm histone retention
01/04/2018
Impact of paternal cholestasis on the BMI, hip and waist girth of their adolescent / young adult children
01/04/2018
Impact of paternal cholestasis on the general health of their adolescent / young adult children
The prevalence of heart, lung, diabetes, thyroid, kidney or liver disease in children of fathers with cholestasis will be investigated
01/04/2018
Secondary Outcomes (1)
Impact of male cholestasis on seminal fluid composition.
01/04/2018
Study Arms (4)
Sperm Epigenome arm/healthy men
Men with no significant health problems.
Sperm Epigenome arm/cholestatic men
Men with a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis.
Outcomes arm/Cholestatic fathers
Fathers who were diagnosed with a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis either before or after the conception of their child who is now aged 16 - 25 years of age.
Outcomes arm/Children of cholestatic fathers
16 - 25 years-old children of fathers who were diagnosed with a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis either before or after their conception.
Interventions
Participants are asked to complete a questionnaire and provide a semen sample and fasting blood sample.
Participants are asked to complete a questionnaire.
Participants are asked to complete a questionnaire and provide a fasting blood sample.
Eligibility Criteria
Men with cholestatic liver conditions including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis. Fathers with cholestatic liver conditions including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis and their children aged 16 - 25 yeas of age.
You may qualify if:
- Men who have a diagnosis of a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis.
- Me who are able and willing to give informed consent.
You may not qualify if:
- Men who have a history of diabetes or obesity.
- Men who have gallstones, cancer or other acute cholestatic pathology.
- Men who have a history of alcohol excess or drug abuse.
- Men who smoke.
- Men who have blood-borne viruses e.g. HIV or hepatitis.
- Men unable or unwilling to give informed consent
- Healthy men
- Men who have no history of cholestasis, liver disease, diabetes or obesity.
- Me who are able and willing to give informed consent.
- Men who have a history of cholestasis or liver disease.
- Men who have a history of diabetes or obesity.
- Men who have a history of alcohol excess or drug abuse.
- Men who smoke.
- Men who have blood-borne viruses e.g. HIV or hepatitis.
- Men undergoing fertility treatment due to male factor.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Assisted Conception Unit, Guy's Hospital
London, SE1 9RT, United Kingdom
King's College Hospital
London, SE5 9RS, United Kingdom
Biospecimen
Sperm Epigenome arm: A semen sample and blood sample will be retained for study purposes. Outcomes arm: A blood sample will be retained for study purposes.
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 1, 2017
First Posted
November 8, 2017
Study Start
February 8, 2017
Primary Completion
April 30, 2020
Study Completion
April 30, 2020
Last Updated
August 2, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will not share