Serum Bile Acid Profiles in Patients With Intrahepatic Cholestasis of Pregnancy

NCT07428226 | Recruiting DMC

• 1 other identifier: Reg.-Nr.: 2023-2917-Material
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn if analyzing bile acid patterns can help predict dangerous complications in pregnant women with intrahepatic cholestasis of pregnancy (ICP), a liver condition that can affect the baby. The main questions it aims to answer are:

• Can measuring specific types of bile acids (particularly taurine-conjugated versus glycine-conjugated bile acids) in the mother's and baby's blood help predict the risk of stillbirth and other complications?
• Do these bile acid patterns activate specific receptors (TGR5) that might contribute to immune problems or heart rhythm abnormalities in the baby?
• How do bile acid patterns in the mother's stool relate to her gut bacteria and the severity of ICP?
• Can heart rate monitoring (CTG) combined with bile acid measurements better identify high-risk pregnancies? ICP is a pregnancy-related liver condition that causes bile acids to build up in the mother's bloodstream. This can lead to serious risks for the baby, including an increased chance of stillbirth, premature birth, and heart rhythm problems. Current monitoring methods (such as heart rate monitoring and ultrasound) often don't show warning signs before complications occur. Participants will:
• Provide blood samples at each routine bile acid check during pregnancy and at delivery
• Provide stool samples for analyzing gut bacteria and bile acids
• Have their baby's umbilical cord blood collected at birth for bile acid analysis
• Undergo standard heart rate monitoring (CTG) of the baby
• Have ultrasound examination of the baby's heart (echocardiography) The study will compare three groups: pregnant women with ICP, healthy pregnant women, and healthy non-pregnant women. The researchers hope this information will help doctors better predict which pregnancies need more intensive monitoring and potentially prevent stillbirths and other complications in women with ICP.

Conditions

Intrahepatic Cholestasis of Pregnancy

Keywords

Intrahepatic Cholestasis of pregnancy; Bile acid profile

Outcome Measures

Primary Outcomes (1)

• bile acid profile

  Qualitative and quantitative bile acid profile in serum of mother and infant (umbilical cord blood)

  Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

Secondary Outcomes (3)

• TGR-5 activity

  Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

• bile acid profile in stool

  Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

• materno-fetal bile acid transfer rate (bile acid profile)

  Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

Other Outcomes (1)

• Correlation between bile acid profiles and TGR5 activation

  Pregnant women: from inclusion to delivery; Non-pregnant female volunteers: at inclusion

Study Arms (3)

Pregnant ICP patients

Diagnosis or suspicion of an ICP according to Hagenbeck et al. 2021

Healthy pregnant controls

Healthy patients with a confirmed pregnancy

Healthy non-pregnant controls

Healthy woman which are not pregnant

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Group 1: Participants in this group are pregnant women diagnosed with or suspected of having ICP who are being treated at the Clinic for Obstetrics, University Hospital Jena, as part of routine clinical care. Group 2: Participants in this group are healthy pregnant women without ICP who are receiving routine prenatal care at the Clinic for Obstetrics, University Hospital Jena. Group 3: Participants in this group are healthy, non-pregnant female volunteers participating in the study independently of the clinical care setting.

You may qualify if:

• Minimum age of 18 years
• Written informed consent
• Pregnant patients with suspected ICP
• Pregnant patients with confirmed ICP
• Pregnant patients with elevated total bile acids (\>14 µmol/ml)
• Pregnant patients with elevated liver enzymes
• Pregnant patients that suffer from itching with elevated transaminases
• Minimum age of 18 years
• Confirmed pregnancy
• Written informed consent
• Generally considered healthy in common usage (corresponding to ASA II of the American Society of Anesthesiologists classification)
• Minimum age of 18 years
• Female gender
• Pregnancy excluded
• Written informed consent

You may not qualify if:

• Age \<18 years
• Inability to provide informed consent
• Signs of an acute illness (for control groups II and III)
• Known liver, biliary, or pancreatic diseases (for control groups II and III)
• ICP in personal or family medical history (for control groups II and III)

Sponsors & Collaborators

• Jena University Hospital: lead

Study Sites (1)

Klinik für Geburtsmedizin, Universitätsklinikum Jena

Jena, Thuringia, 07747, Germany

RECRUITING

Related Publications (30)

• Hagenbeck C, Hamza A, Kehl S, Maul H, Lammert F, Keitel V, et al. Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders. Geburtshilfe Frauenheilkd. 2021;81(8):922-39.

  BACKGROUND

• Shao Y, Yao Z, Lu J, Li H, Wu W, Ding M. [Change of heart rate power spectrum and its association with sudden death in the fetuses of rats with intrahepatic cholestasis of pregnancy]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2007;24(6):1215-9.

  BACKGROUND

• Vasavan T, Deepak S, Jayawardane IA, Lucchini M, Martin C, Geenes V, et al. Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations. J Hepatol. 2021;74(5):1087-96.

  BACKGROUND

• Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet. 2006;93(1):53-4.

  BACKGROUND

• Katsidzira L, Ocvirk S, Wilson A, Li J, Mahachi CB, Soni D, et al. Differences in Fecal Gut Microbiota, Short-Chain Fatty Acids and Bile Acids Link Colorectal Cancer Risk to Dietary Changes Associated with Urbanization Among Zimbabweans. Nutr Cancer. 2019;71(8):1313-24.

  BACKGROUND

• Li X, Xie H, Chao JJ, Jia YH, Zuo J, An YP, et al. Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy. BMC Microbiol. 2023;23(1):282.

  BACKGROUND

• Staley C, Weingarden AR, Khoruts A, Sadowsky MJ. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl Microbiol Biotechnol. 2017;101(1):47-64.

  BACKGROUND

• Wahlstrom A, Sayin SI, Marschall HU, Backhed F. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. Cell Metab. 2016 Jul 12;24(1):41-50. doi: 10.1016/j.cmet.2016.05.005. Epub 2016 Jun 16.

  PMID: 27320064 BACKGROUND

• Lin Z, Wu J, Wang J, Levesque CL, Ma X. Dietary Lactobacillus reuteri prevent from inflammation mediated apoptosis of liver via improving intestinal microbiota and bile acid metabolism. Food Chem. 2023;404(Pt B):134643.

  BACKGROUND

• Martinez-Gili L, Pechlivanis A, McDonald JAK, Begum S, Badrock J, Dyson JK, et al. Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis. Gut Microbes. 2023;15(1):2208501.

  BACKGROUND

• Zhang X, Han S, Jiang X, Duan S, Gao Y, Ding J, et al. Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection. Front Cell Infect Microbiol. 2023;13:1254016.

  BACKGROUND

• Ryan PM, Stanton C, Caplice NM. Bile acids at the cross-roads of gut microbiome-host cardiometabolic interactions. Diabetol Metab Syndr. 2017;9:102.

  BACKGROUND

• Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014;30(3):332-8.

  BACKGROUND

• Klinke P, Kurtz, Silbernagel (Hrsg.). Physiologie. In: Klinke, editor. Physiologie: Thieme; 2010. p. 471, 5.

  BACKGROUND

• Leonhardt J, Haider RS, Sponholz C, Leonhardt S, Drube J, Spengler K, et al. Circulating Bile Acids in Liver Failure Activate TGR5 and Induce Monocyte Dysfunction. Cell Mol Gastroenterol Hepatol. 2021;12(1):25-40.

  BACKGROUND

• de Vries E, Bolier R, Goet J, Pares A, Verbeek J, de Vree M, et al. Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial. Gastroenterology. 2021;160(3):734-43 e6.

  BACKGROUND

• Poupon RE, Chretien Y, Poupon R, Paumgartner G. Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. Hepatology. 1993;17(4):599-604.

  BACKGROUND

• Trottier J, Bialek A, Caron P, Straka RJ, Heathcote J, Milkiewicz P, et al. Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study. Dig Liver Dis. 2012;44(4):303-10.

  BACKGROUND

• Horvatits T, Drolz A, Roedl K, Rutter K, Ferlitsch A, Fauler G, et al. Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis. Liver Int. 2017;37(2):224-31.

  BACKGROUND

• Manna LB, Ovadia C, Lovgren-Sandblom A, Chambers J, Begum S, Seed P, et al. Enzymatic quantification of total serum bile acids as a monitoring strategy for women with intrahepatic cholestasis of pregnancy receiving ursodeoxycholic acid treatment: a cohort study. BJOG. 2019;126(13):1633-40.

  BACKGROUND

• Sepúlveda WH, González C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol. 1991;42(3):211-5.

  BACKGROUND

• Williamson C, Miragoli M, Sheikh Abdul Kadir S, Abu-Hayyeh S, Papacleovoulou G, Geenes V, et al. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis. 2011;29(1):58-61.

  BACKGROUND

• Gorelik J, Shevchuk A, de Swiet M, Lab M, Korchev Y, Williamson C. Comparison of the arrhythmogenic effects of tauro- and glycoconjugates of cholic acid in an in vitro study of rat cardiomyocytes. BJOG: An International Journal of Obstetrics & Gynaecology. 2004;111(8):867-70.

  BACKGROUND

• Geenes V, Lövgren-Sandblom A, Benthin L, Lawrance D, Chambers J, Gurung V, et al. The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid. PLoS One. 2014;9(1):e83828.

  BACKGROUND

• Joutsiniemi T, Ekblad U, Rosén KG, Timonen S. Waveform analysis of the fetal ECG in labor in patients with intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Res. 2019;45(2):306-12.

  BACKGROUND

• Toprak V, Kafadar MT. Intrahepatic cholestasis of pregnancy: Is fetoplacental doppler ultrasound useful in the diagnosis and follow-up? 2021;12:87-91.

  BACKGROUND

• Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology. 2004;40(2):467-74.

  BACKGROUND

• Blencowe H, Cousens S, Jassir FB, Say L, Chou D, Mathers C, et al. National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health. 2016;4(2):e98-e108.

  BACKGROUND

• Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019;393(10174):899-909.

  BACKGROUND

• Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009;15(17):2049-66.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, stool, placenta

MeSH Terms

Conditions

Intrahepatic Cholestasis of Pregnancy

Study Officials

• Tanja Groten, Prof. Dr. med.

  University Hospital Jena

  STUDY CHAIR

Central Study Contacts

Silke Große, Dr. rer. nat.

CONTACT

+493641 9-329293; silke.grosse@med.uni-jena.de

Janine Zöllkau, Dr. med.

CONTACT

janine.zoellkau@med.uni-jena.de

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: February 23, 2026
• Study Start: July 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

DE (1)