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Paternally Inherited Phenotypes in Cholestasis (PIP-C)

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ClinicalTrials.gov Identifier: NCT03337074
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : August 2, 2019
Sponsor:
Collaborator:
King's College Hospital NHS Trust
Information provided by (Responsible Party):
Guy's and St Thomas' NHS Foundation Trust

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.


Condition or disease Intervention/treatment
Cholestasis Primary Sclerosing Cholangitis Primary Biliary Cirrhosis Other: Questionnaire, semen sample, fasting blood sample Other: Questionnaire Other: Questionnaire, fasting blood sample

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: 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.
Actual Study Start Date : February 8, 2017
Estimated Primary Completion Date : April 30, 2020
Estimated Study Completion Date : April 30, 2020


Group/Cohort Intervention/treatment
Sperm Epigenome arm/healthy men
Men with no significant health problems.
Other: Questionnaire, semen sample, fasting blood sample
Participants are asked to complete a questionnaire and provide a semen sample and fasting blood sample.

Sperm Epigenome arm/cholestatic men
Men with a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis.
Other: Questionnaire, semen sample, fasting blood sample
Participants are asked to complete a questionnaire and provide a semen sample and fasting blood sample.

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.
Other: Questionnaire
Participants are asked to complete a questionnaire.

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.
Other: Questionnaire, fasting blood sample
Participants are asked to complete a questionnaire and provide a fasting blood sample.




Primary Outcome Measures :
  1. Impact of male cholestasis on DNA methylation patterns in sperm [ Time Frame: 01/04/2018 ]
  2. Impact of male cholestasis on small RNA content in sperm [ Time Frame: 01/04/2018 ]
  3. Impact of male cholestasis on sperm histone retention [ Time Frame: 01/04/2018 ]
  4. Impact of paternal cholestasis on the BMI, hip and waist girth of their adolescent / young adult children [ Time Frame: 01/04/2018 ]
  5. Impact of paternal cholestasis on the general health of their adolescent / young adult children [ Time Frame: 01/04/2018 ]
    The prevalence of heart, lung, diabetes, thyroid, kidney or liver disease in children of fathers with cholestasis will be investigated


Secondary Outcome Measures :
  1. Impact of male cholestasis on seminal fluid composition. [ Time Frame: 01/04/2018 ]

Biospecimen Retention:   Samples With DNA

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.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

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.

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.

Exclusion Criteria:

  • 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.
  • Men unable or unwilling to give informed consent

Outcomes Arm:

Fathers

Inclusion Criteria:

  • Fathers with a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis and Primary Biliary Cholangitis.
  • Fathers with cholestatic liver condition whose children are between 16 years - 25 years of age.
  • Fathers with cholestatic liver condition who are able and willing to give informed consent.

Exclusion Criteria:

  • Fathers with a history of diabetes or obesity at the time of conception of their child.
  • Fathers with a history of alcohol excess or drug-abuse at the time of conception of their child.
  • Fathers who smoked at the time of conception of their child.
  • Fathers with blood-borne viruses e.g. HIV and hepatitis at the time of conception of their child.
  • Fathers unable or unwilling to give informed consent.

Children of cholestatic fathers

Inclusion Criteria:

  • Adolescents / young adults (between 16 - 25 years of age) whose fathers have a cholestatic liver condition including but not restricted to Primary Sclerosing Cholangitis or Primary Biliary Cholangitis.
  • Adolescents /young adults born from an uncomplicated singleton pregnancy.
  • Adolescents /young adults who are able and willing to give informed consent.

Exclusion Criteria:

  • Adolescents / young adults who were born as a result of multi-fetal pregnancy.
  • Adolescents / young adults with a history of alcohol excess or drug-abuse.
  • Adolescents / young adults who are under 16 years of age, or over 25 years of age.
  • Adolescents / young adults with blood-borne viruses e.g. HIV and hepatitis.
  • Adolescents / young adults who are unable or unwilling to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03337074


Contacts
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Contact: Saraid McIlvride 02078486202 saraid.a.mcilvride@kcl.ac.uk
Contact: Catherine Williamson catherine.williamson@kcl.ac.uk

Locations
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United Kingdom
Assisted Conception Unit, Guy's Hospital Recruiting
London, United Kingdom, SE1 9RT
Contact: Jean Bvumbe       Jean.Bvumbe@gstt.nhs.uk   
King's College Hospital Recruiting
London, United Kingdom, SE5 9RS
Contact: Bernadette Solis    02032991495    bernadette.solis@nhs.net   
Sponsors and Collaborators
Guy's and St Thomas' NHS Foundation Trust
King's College Hospital NHS Trust

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Responsible Party: Guy's and St Thomas' NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03337074     History of Changes
Other Study ID Numbers: 182833
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangitis
Cholestasis
Cholangitis, Sclerosing
Liver Cirrhosis, Biliary
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Liver Diseases
Liver Cirrhosis