CClinicalTrials.gg
RecruitingNCT07428226BAPPUpdated Feb 23, 2026

Serum Bile Acid Profiles in Patients With Intrahepatic Cholestasis of Pregnancy

An observational study in Intrahepatic Cholestasis of Pregnancy, sponsored by Jena University Hospital. Recruiting at 1 site in Germany. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-02-23.

Sponsored by Jena University Hospital · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
74
Ages
18 Years to 45 Years
Sex
Female
01

Study 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.
02

Conditions studied

  • Intrahepatic Cholestasis of Pregnancy

Keywords

  • Intrahepatic Cholestasis of pregnancy
  • Bile acid profile
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes
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.

Eligibility criteria

Inclusion Criteria Group I:

  • 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

Inclusion Criteria Group II:

  • 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)

Inclusion Criteria Group III:

  • Minimum age of 18 years
  • Female gender
  • Pregnancy excluded
  • Written informed consent
  • Generally considered healthy in common usage (corresponding to ASA II of the American Society of Anesthesiologists classification)

Exclusion Criteria Group II and III:

  • 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)
04

Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
74 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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

05

What researchers measure

Primary outcomes

  1. bile acid profile

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

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

Secondary outcomes

  1. TGR-5 activity

    TGR5 activation by immunosuppressive bile acids calculated according to published protocols (Leonhardt et al. 2021)

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

  2. bile acid profile in stool

    The bile acid profile in stool is an exploratory outcome measure that examines the composition and concentration of various bile acids in stool samples.

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

  3. materno-fetal bile acid transfer rate (bile acid profile)

    The maternal-fetal bile acid transfer rate describes the extent and efficiency with which bile acids pass from the mother through the placenta into the fetal circulation (placental permeability).

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

Other outcomes

  1. Correlation between bile acid profiles and TGR5 activation

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

06

Study locations

1 of 1 sites recruiting
07

References and documents

Publications

  • Hagenbeck C, Hamza A, Kehl S, Maul H, Lammert F, Keitel V, Hutten MC, Pecks U. Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders. Geburtshilfe Frauenheilkd. 2021 Aug;81(8):922-939. doi: 10.1055/a-1386-3912. Epub 2021 Aug 9. PubMed 34393256 ↗
  • 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 Dec;24(6):1215-9. Chinese. PubMed 18232463 ↗
  • Vasavan T, Deepak S, Jayawardane IA, Lucchini M, Martin C, Geenes V, Yang J, Lovgren-Sandblom A, Seed PT, Chambers J, Stone S, Kurlak L, Dixon PH, Marschall HU, Gorelik J, Chappell L, Loughna P, Thornton J, Pipkin FB, Hayes-Gill B, Fifer WP, Williamson C. Fetal cardiac dysfunction in intrahepatic cholestasis of pregnancy is associated with elevated serum bile acid concentrations. J Hepatol. 2021 May;74(5):1087-1096. doi: 10.1016/j.jhep.2020.11.038. Epub 2020 Dec 1. PubMed 33276032 ↗
  • Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet. 2006 Apr;93(1):53-4. doi: 10.1016/j.ijgo.2005.12.030. Epub 2006 Mar 9. No abstract available. PubMed 16527280 ↗
  • Katsidzira L, Ocvirk S, Wilson A, Li J, Mahachi CB, Soni D, DeLany J, Nicholson JK, Zoetendal EG, O'Keefe SJD. 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):1313-1324. doi: 10.1080/01635581.2019.1602659. Epub 2019 Apr 22. PubMed 31007075 ↗
  • Li X, Xie H, Chao JJ, Jia YH, Zuo J, An YP, Bao YR, Jiang X, Ying H. Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy. BMC Microbiol. 2023 Oct 3;23(1):282. doi: 10.1186/s12866-023-02983-x. PubMed 37784030 ↗
  • 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 Jan;101(1):47-64. doi: 10.1007/s00253-016-8006-6. Epub 2016 Nov 25. PubMed 27888332 ↗
  • 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. PubMed 27320064 ↗
  • 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 Mar 15;404(Pt B):134643. doi: 10.1016/j.foodchem.2022.134643. Epub 2022 Oct 18. PubMed 36283304 ↗
  • Martinez-Gili L, Pechlivanis A, McDonald JAK, Begum S, Badrock J, Dyson JK, Jones R, Hirschfield G, Ryder SD, Sandford R, Rushbrook S, Thorburn D, Taylor-Robinson SD, Crossey MME, Marchesi JR, Mells G, Holmes E, Jones D. Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis. Gut Microbes. 2023 Jan-Dec;15(1):2208501. doi: 10.1080/19490976.2023.2208501. PubMed 37191344 ↗
  • Zhang X, Han S, Jiang X, Duan S, Gao Y, Ding J, Li X, Sun B, Hu X, Zhang X, Zhang W. Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection. Front Cell Infect Microbiol. 2023 Sep 12;13:1254016. doi: 10.3389/fcimb.2023.1254016. eCollection 2023. PubMed 37868349 ↗
  • Ryan PM, Stanton C, Caplice NM. Bile acids at the cross-roads of gut microbiome-host cardiometabolic interactions. Diabetol Metab Syndr. 2017 Dec 28;9:102. doi: 10.1186/s13098-017-0299-9. eCollection 2017. PubMed 29299069 ↗
  • Ridlon JM, Kang DJ, Hylemon PB, Bajaj JS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014 May;30(3):332-8. doi: 10.1097/MOG.0000000000000057. PubMed 24625896 ↗
  • Klinke P, Kurtz, Silbernagel (Hrsg.). Physiologie. In: Klinke, editor. Physiologie: Thieme; 2010. p. 471, 5.
  • Leonhardt J, Haider RS, Sponholz C, Leonhardt S, Drube J, Spengler K, Mihaylov D, Neugebauer S, Kiehntopf M, Lambert NA, Kortgen A, Bruns T, Tacke F, Hoffmann C, Bauer M, Heller R. Circulating Bile Acids in Liver Failure Activate TGR5 and Induce Monocyte Dysfunction. Cell Mol Gastroenterol Hepatol. 2021;12(1):25-40. doi: 10.1016/j.jcmgh.2021.01.011. Epub 2021 Feb 2. PubMed 33545429 ↗
  • de Vries E, Bolier R, Goet J, Pares A, Verbeek J, de Vree M, Drenth J, van Erpecum K, van Nieuwkerk K, van der Heide F, Mostafavi N, Helder J, Ponsioen C, Oude Elferink R, van Buuren H, Beuers U; Netherlands Association for the Study of the Liver-Cholestasis Working Group. Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial. Gastroenterology. 2021 Feb;160(3):734-743.e6. doi: 10.1053/j.gastro.2020.10.001. Epub 2020 Oct 5. PubMed 33031833 ↗
  • Poupon RE, Chretien Y, Poupon R, Paumgartner G. Serum bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid therapy. Hepatology. 1993 Apr;17(4):599-604. doi: 10.1002/hep.1840170412. PubMed 8477964 ↗
  • Trottier J, Bialek A, Caron P, Straka RJ, Heathcote J, Milkiewicz P, Barbier O. 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 Apr;44(4):303-10. doi: 10.1016/j.dld.2011.10.025. Epub 2011 Dec 9. PubMed 22169272 ↗
  • Horvatits T, Drolz A, Roedl K, Rutter K, Ferlitsch A, Fauler G, Trauner M, Fuhrmann V. Serum bile acids as marker for acute decompensation and acute-on-chronic liver failure in patients with non-cholestatic cirrhosis. Liver Int. 2017 Feb;37(2):224-231. doi: 10.1111/liv.13201. Epub 2016 Aug 4. PubMed 27416294 ↗
  • Manna LB, Ovadia C, Lovgren-Sandblom A, Chambers J, Begum S, Seed P, Walker I, Chappell LC, Marschall HU, Williamson C. 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 Dec;126(13):1633-1640. doi: 10.1111/1471-0528.15926. Epub 2019 Sep 26. PubMed 31483939 ↗
  • Sepulveda WH, Gonzalez C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol. 1991 Dec 13;42(3):211-5. doi: 10.1016/0028-2243(91)90222-7. PubMed 1773876 ↗
  • Williamson C, Miragoli M, Sheikh Abdul Kadir S, Abu-Hayyeh S, Papacleovoulou G, Geenes V, Gorelik J. Bile acid signaling in fetal tissues: implications for intrahepatic cholestasis of pregnancy. Dig Dis. 2011;29(1):58-61. doi: 10.1159/000324130. Epub 2011 Jun 17. PubMed 21691106 ↗
  • 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. 2004 Aug;111(8):867-70. doi: 10.1111/j.1471-0528.2004.00166.x. PubMed 15270939 ↗
  • Geenes V, Lovgren-Sandblom A, Benthin L, Lawrance D, Chambers J, Gurung V, Thornton J, Chappell L, Khan E, Dixon P, Marschall HU, Williamson C. The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid. PLoS One. 2014 Jan 8;9(1):e83828. doi: 10.1371/journal.pone.0083828. eCollection 2014. PubMed 24421907 ↗
  • Joutsiniemi T, Ekblad U, Rosen KG, Timonen S. Waveform analysis of the fetal ECG in labor in patients with intrahepatic cholestasis of pregnancy. J Obstet Gynaecol Res. 2019 Feb;45(2):306-312. doi: 10.1111/jog.13812. Epub 2018 Sep 11. PubMed 30203501 ↗
  • Toprak V, Kafadar MT. Intrahepatic cholestasis of pregnancy: Is fetoplacental doppler ultrasound useful in the diagnosis and follow-up? 2021;12:87-91.
  • Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology. 2004 Aug;40(2):467-74. doi: 10.1002/hep.20336. PubMed 15368452 ↗
  • Blencowe H, Cousens S, Jassir FB, Say L, Chou D, Mathers C, Hogan D, Shiekh S, Qureshi ZU, You D, Lawn JE; Lancet Stillbirth Epidemiology Investigator Group. National, regional, and worldwide estimates of stillbirth rates in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health. 2016 Feb;4(2):e98-e108. doi: 10.1016/S2214-109X(15)00275-2. Epub 2016 Jan 19. PubMed 26795602 ↗
  • Ovadia C, Seed PT, Sklavounos A, Geenes V, Di Ilio C, Chambers J, Kohari K, Bacq Y, Bozkurt N, Brun-Furrer R, Bull L, Estiu MC, Grymowicz M, Gunaydin B, Hague WM, Haslinger C, Hu Y, Kawakita T, Kebapcilar AG, Kebapcilar L, Kondrackiene J, Koster MPH, Kowalska-Kanka A, Kupcinskas L, Lee RH, Locatelli A, Macias RIR, Marschall HU, Oudijk MA, Raz Y, Rimon E, Shan D, Shao Y, Tribe R, Tripodi V, Yayla Abide C, Yenidede I, Thornton JG, Chappell LC, Williamson C. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019 Mar 2;393(10174):899-909. doi: 10.1016/S0140-6736(18)31877-4. Epub 2019 Feb 14. PubMed 30773280 ↗
  • Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009 May 7;15(17):2049-66. doi: 10.3748/wjg.15.2049. PubMed 19418576 ↗

Individual participant data

Plan to share: Undecided — * The data concerns a vulnerable population (pregnant individuals and their newborns), which is why personal information is treated with particular sensitivity. * The local data protection policy must be observed. * In scientific cooperation, a release is conceivable after careful review and in accordance with legal, ethical, and organizational requirements.

08

Registry details

Key details

Study ID
NCT07428226
Lead sponsor
Jena University Hospital
Responsible party
Sponsor
First posted
Feb 23, 2026
Start date
Jul 1, 2024
Primary completion
Dec 31, 2026 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Feb 23, 2026

Study contacts

Silke Große, Dr. rer. nat.
Contact
silke.grosse@med.uni-jena.de
+493641 9-329293
Janine Zöllkau, Dr. med.
Contact
janine.zoellkau@med.uni-jena.de
Tanja Groten, Prof. Dr. med.
study chair · University Hospital Jena

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion