Cholestasis, Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis
Conditions
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.
Interventions
OTHERQuestionnaire, semen sample, fasting blood sample
Participants are asked to complete a questionnaire and provide a semen sample and fasting blood sample.
OTHERQuestionnaire
Participants are asked to complete a questionnaire.
OTHERQuestionnaire, fasting blood sample
Participants are asked to complete a questionnaire and provide a fasting blood sample.
Sponsors
King's College Hospital NHS Trust
Guy's and St Thomas' NHS Foundation Trust
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Sperm Epigenome Arm: Cholestatic men Inclusion Criteria: * 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.
Exclusion criteria
* 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 Inclusion Criteria: * Men who have no history of cholestasis, liver disease, diabetes or obesity. * Me who are able and willing to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 01/04/2018 | The prevalence of heart, lung, diabetes, thyroid, kidney or liver disease in children of fathers with cholestasis will be investigated |
Secondary
| Measure | Time frame |
|---|---|
| Impact of male cholestasis on seminal fluid composition. | 01/04/2018 |
Countries
United Kingdom
Contacts
Primary ContactSaraid McIlvride
Backup ContactCatherine Williamson
Outcome results
None listed