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出境医 / 临床实验 / Bile Composition in Healthy and Gallstones Patients

Bile Composition in Healthy and Gallstones Patients

Study Description
Brief Summary:
Determine differences between lithogenic and non-lithogenic bile composition.

Condition or disease Intervention/treatment
Cholelithiasis Gall Stone Gall Bladder Disease Diagnostic Test: Bile test Diagnostic Test: Blood test Diagnostic Test: Gall stone study Diagnostic Test: Microbiological bile test

Detailed Description:

Gallstones constitute an entity known from antiquity, which have been found even in Egyptian mummies. In elder Greece, Tralliano discovered that gallstones are formed in the liver. Vesalio and Falopio described gallstones inside de gallbladder after a human body dissection and in 1882 Langenbuch performed the first cholecystectomy with good results, becoming the gold standard technique for cholelithiasis.

Nowadays, this pathology represents a public health problem in developed countries due to its high prevalence, which is getting higher, estimated between a 10 and a 15% of the population.

However, gallstones are asymptomatic in the 80% of the cases. In 5 years, a 10-20% of these patients will become symptomatic. The global risk of generating symptoms is about a 2% per year, meanwhile biliary tract complications in asymptomatic patients represent a 0'3% per year.

There are two main types of gallstones. The most common of them (70%) are cholesterol stones, composed of >50% of cholesterol. The other 30% are black pigment stones, with less than 20% of cholesterol in their composition.

The common ways on gallstone formation are: cholesterol supersaturation (due to a liver oversecretion); defects on gallbladder absorption, secretion and motility mechanisms; and higher percentage of deoxycholic acid in the biliary acids due to a slower intestinal movement. All of that leads to supersaturation and cholesterol nucleation.

Black pigment stones are formed of calcium bilirrubinate. The formation mechanism is not clearly defined, but there is an increment in not conjugated bilirubin levels, which is less soluble in water. These gallstones are more frequent in patients who show higher levels of this bilirubin, such as those with hemolysis, Gilbert syndrome or hereditary spherocytosis. They are also common in patients with Crohn disease (specially in those with ileal resection) and cystic fibrosis, in which exists an enterohepatic circulation alteration, driving to an increase on biliary salts and non-conjugated bilirubin levels.

Our work hypothesis is that bile composition in patients with gallstones on the gallbladder is different from those who doesn't show lithiasis.

Study Design
Layout table for study information
Study Type : Observational [Patient Registry]
Estimated Enrollment : 62 participants
Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: Gallbladder Bile Composition in Patients With Gallstones and Healthy Patients
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : June 2022
Arms and Interventions
Group/Cohort Intervention/treatment
Lithogenic bile in symptomatic patient
Patients who are performed a cholecystectomy as a treatment of their gallbladder disease
Diagnostic Test: Bile test
Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)

Diagnostic Test: Blood test
Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)

Diagnostic Test: Gall stone study
Study of the extracted gall stones, analyzing their composition, type, etc.

Diagnostic Test: Microbiological bile test
Determination of the microbiological composition of the bile

Lithogenic bile in asymptomatic patient
Patients who are performed a cholecystectomy for another reason (cancer, organ donation) and gall stones are found
Diagnostic Test: Bile test
Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)

Diagnostic Test: Blood test
Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)

Diagnostic Test: Gall stone study
Study of the extracted gall stones, analyzing their composition, type, etc.

Diagnostic Test: Microbiological bile test
Determination of the microbiological composition of the bile

Non-lithogenic bile
Patients who are performed a cholecystectomy for another reason (cancer, organ donation) without gall stones
Diagnostic Test: Bile test
Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)

Diagnostic Test: Blood test
Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)

Diagnostic Test: Microbiological bile test
Determination of the microbiological composition of the bile

Outcome Measures
Primary Outcome Measures :
  1. Differences of bile composition between cases and controls [ Time Frame: Intra-operatively ]
    Bilirrubine in mg/dL


Biospecimen Retention:   Samples With DNA
Bile and blood

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   16 Years to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
It includes patients who suffer from gallstones, which are operated for that reason (open or laparoscopic cholecystectomy), and patients who go through the same intervention for other reasons (cancer, organ donation)
Criteria

Inclusion Criteria for the Study Group:

  1. Patients included for an elective cholecystectomy.
  2. Normal hepatic and renal function.
  3. Able to understand the nature of the study.
  4. Wish to participate in the study and sign the informed consent.

Inclusion Criteria for the Control Group:

  1. Patients included for an hepatectomy with gallbladder exeresis for surgery reasons, without lithiasis.
  2. Patients included for peritoneal carcinomatosis surgery with gallbladder exeresis for surgery reasons, without lithiasis.
  3. Organ donors.
  4. Normal hepatic and renal function.
  5. Able to understand the nature of the study.
  6. Wish to participate in the study and sign the informed consent.

Exclusion Criteria:

  1. Under 16 years old
  2. Hepatic or renal insufficiency
  3. Impossibility to understand the aim of the study
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Alejandro Gil Catalán 695621497 alejandro.gil@ssib.es
Contact: Francesc Xavier Molina Romero 695621497 xmolina@ssib.es

Locations
Layout table for location information
Spain
Hospital Universitario Son Espases
Palma De Mallorca, Mallorca, Spain, 07010
Contact: Alejandro Gil Catalán    695621497    alejandro.gil@ssib.es   
Sponsors and Collaborators
Hospital Son Espases
Tracking Information
First Submitted Date June 4, 2019
First Posted Date June 10, 2019
Last Update Posted Date June 10, 2019
Estimated Study Start Date October 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 7, 2019)
Differences of bile composition between cases and controls [ Time Frame: Intra-operatively ]
Bilirrubine in mg/dL
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Bile Composition in Healthy and Gallstones Patients
Official Title Gallbladder Bile Composition in Patients With Gallstones and Healthy Patients
Brief Summary Determine differences between lithogenic and non-lithogenic bile composition.
Detailed Description

Gallstones constitute an entity known from antiquity, which have been found even in Egyptian mummies. In elder Greece, Tralliano discovered that gallstones are formed in the liver. Vesalio and Falopio described gallstones inside de gallbladder after a human body dissection and in 1882 Langenbuch performed the first cholecystectomy with good results, becoming the gold standard technique for cholelithiasis.

Nowadays, this pathology represents a public health problem in developed countries due to its high prevalence, which is getting higher, estimated between a 10 and a 15% of the population.

However, gallstones are asymptomatic in the 80% of the cases. In 5 years, a 10-20% of these patients will become symptomatic. The global risk of generating symptoms is about a 2% per year, meanwhile biliary tract complications in asymptomatic patients represent a 0'3% per year.

There are two main types of gallstones. The most common of them (70%) are cholesterol stones, composed of >50% of cholesterol. The other 30% are black pigment stones, with less than 20% of cholesterol in their composition.

The common ways on gallstone formation are: cholesterol supersaturation (due to a liver oversecretion); defects on gallbladder absorption, secretion and motility mechanisms; and higher percentage of deoxycholic acid in the biliary acids due to a slower intestinal movement. All of that leads to supersaturation and cholesterol nucleation.

Black pigment stones are formed of calcium bilirrubinate. The formation mechanism is not clearly defined, but there is an increment in not conjugated bilirubin levels, which is less soluble in water. These gallstones are more frequent in patients who show higher levels of this bilirubin, such as those with hemolysis, Gilbert syndrome or hereditary spherocytosis. They are also common in patients with Crohn disease (specially in those with ileal resection) and cystic fibrosis, in which exists an enterohepatic circulation alteration, driving to an increase on biliary salts and non-conjugated bilirubin levels.

Our work hypothesis is that bile composition in patients with gallstones on the gallbladder is different from those who doesn't show lithiasis.

Study Type Observational [Patient Registry]
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration 2 Years
Biospecimen Retention:   Samples With DNA
Description:
Bile and blood
Sampling Method Non-Probability Sample
Study Population It includes patients who suffer from gallstones, which are operated for that reason (open or laparoscopic cholecystectomy), and patients who go through the same intervention for other reasons (cancer, organ donation)
Condition
  • Cholelithiasis
  • Gall Stone
  • Gall Bladder Disease
Intervention
  • Diagnostic Test: Bile test
    Analyze bile components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)
  • Diagnostic Test: Blood test
    Analyze blood components related to gall stones synthesis (cholesterol, bile acids, phospholypids, etc.)
  • Diagnostic Test: Gall stone study
    Study of the extracted gall stones, analyzing their composition, type, etc.
  • Diagnostic Test: Microbiological bile test
    Determination of the microbiological composition of the bile
Study Groups/Cohorts
  • Lithogenic bile in symptomatic patient
    Patients who are performed a cholecystectomy as a treatment of their gallbladder disease
    Interventions:
    • Diagnostic Test: Bile test
    • Diagnostic Test: Blood test
    • Diagnostic Test: Gall stone study
    • Diagnostic Test: Microbiological bile test
  • Lithogenic bile in asymptomatic patient
    Patients who are performed a cholecystectomy for another reason (cancer, organ donation) and gall stones are found
    Interventions:
    • Diagnostic Test: Bile test
    • Diagnostic Test: Blood test
    • Diagnostic Test: Gall stone study
    • Diagnostic Test: Microbiological bile test
  • Non-lithogenic bile
    Patients who are performed a cholecystectomy for another reason (cancer, organ donation) without gall stones
    Interventions:
    • Diagnostic Test: Bile test
    • Diagnostic Test: Blood test
    • Diagnostic Test: Microbiological bile test
Publications *
  • Gibney EJ. Asymptomatic gallstones. Br J Surg. 1990 Apr;77(4):368-72. Review.
  • Heller F, Bouchier IA. Cholesterol and bile salt studies on the bile of patients with cholesterol gallstones. Gut. 1973 Feb;14(2):83-8.
  • Jayanthi V, Sarika S, Varghese J, Vaithiswaran V, Sharma M, Reddy MS, Srinivasan V, Reddy GM, Rela M, Kalkura S. Composition of gallbladder bile in healthy individuals and patients with gallstone disease from north and South India. Indian J Gastroenterol. 2016 Sep;35(5):347-353. Epub 2016 Sep 16.
  • Mackay C, Crook JN, Smith DC, McAllister RA. The composition of hepatic and gallbladder bile in patients with gallstones. Gut. 1972 Oct;13(10):759-62.
  • Reinhold JG, Ferguson LK, Hunsberger A. THE COMPOSITION OF HUMAN GALLBLADDER BILE AND ITS RELATIONSHIP TO CHOLELITHIASIS. J Clin Invest. 1937 May;16(3):367-82.
  • Shaffer EA. Gallstone disease: Epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20(6):981-96. Review.
  • Van Erpecum KJ. Pathogenesis of cholesterol and pigment gallstones: an update. Clin Res Hepatol Gastroenterol. 2011 Apr;35(4):281-7. doi: 10.1016/j.clinre.2011.01.009. Epub 2011 Feb 25. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: June 7, 2019)
62
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 2022
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria for the Study Group:

  1. Patients included for an elective cholecystectomy.
  2. Normal hepatic and renal function.
  3. Able to understand the nature of the study.
  4. Wish to participate in the study and sign the informed consent.

Inclusion Criteria for the Control Group:

  1. Patients included for an hepatectomy with gallbladder exeresis for surgery reasons, without lithiasis.
  2. Patients included for peritoneal carcinomatosis surgery with gallbladder exeresis for surgery reasons, without lithiasis.
  3. Organ donors.
  4. Normal hepatic and renal function.
  5. Able to understand the nature of the study.
  6. Wish to participate in the study and sign the informed consent.

Exclusion Criteria:

  1. Under 16 years old
  2. Hepatic or renal insufficiency
  3. Impossibility to understand the aim of the study
Sex/Gender
Sexes Eligible for Study: All
Ages 16 Years to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Alejandro Gil Catalán 695621497 alejandro.gil@ssib.es
Contact: Francesc Xavier Molina Romero 695621497 xmolina@ssib.es
Listed Location Countries Spain
Removed Location Countries  
 
Administrative Information
NCT Number NCT03981315
Other Study ID Numbers BILISGILMOL
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Hospital Son Espases
Study Sponsor Hospital Son Espases
Collaborators Not Provided
Investigators Not Provided
PRS Account Hospital Son Espases
Verification Date June 2019