UDCA for Symptomatic Gallstone Disease

Brief Title

UDCA for Symptomatic Gallstone Disease

Official Title

Studie Naar De Effectiviteit Van Ursodeoxycholzuur Ter Preventie Van Galsteen-Gerelateerde Klachten Bij patiënten in Afwachting Van Een Cholecystectomie

Brief Summary

      We conduct a randomized, double-blind, placebo-controlled trial on effects of UDCA on biliary
      pain and complications in highly symptomatic gallstone patients scheduled for
      cholecystectomy. We also evaluate potential beneficial effects of impaired gallbladder
      motility

Detailed Description

Gallstone disease is very common with an estimated prevalence of 10-15% in the adult Western
population. Approximately 90% of gallstone carriers are asymptomatic. The annual risk of
biliary colic in asymptomatic gallstone carriers has been suggested to be approximately 1%.
Also, asymptomatic gallstone carriers are at risk for acute pancreatitis, choledocholithiasis
and acute cholecystitis. Although accurate prospective data are lacking, annual incidences of
these potentially lethal complications are estimated to be approximately 0.2%, 0.2% and 0.3%,
respectively.

One can easily imagine that migration of gallbladder stones into the common bile duct may
lead to biliary pain. How gallbladder stones remaining in the gallbladder lead to biliary
symptoms is not entirely clear. Strong gallbladder contraction, with temporary impaction of
the stone in the orifice of the cystic duct might cause biliary pain. Although impaired
gallbladder motility could therefore theoretically protect against colics, symptomatic
gallbladder stone patients often have complaints despite coexistent impaired gallbladder
emptying.

Ursodeoxycholic acid (UDCA) has been claimed to reduce the risk of biliary pain, regardless
of gallstone dissolution. In a large study by Tomida et al., risks of biliary pain or
gallstone complications (acute cholecystitis) were reduced in both symptomatic and
asymptomatic gallstone carriers, although gallstones were generally not dissolved. Also,
biliary pancreatitis might be prevented by long-term UDCA treatment. Increased fasting and
residual postprandial gallbladder volumes during UDCA treatment, less cholesterol crystals or
decreased mucin contents in bile could be the underlying mechanisms for these beneficial
effects. However, prospective studies on effects of UDCA on symptoms or complications in
highly symptomatic patients are lacking.

In the Netherlands symptomatic gallstone patients are admitted to a waiting list for elective
cholecystectomy by general surgeons. The waiting period may last several months because of
logistic reasons. During this waiting period gallstone patients are at risk for biliary pain
and complications. Therefore, we conducted a randomized, double-blind, placebo-controlled
trial on effects of UDCA on biliary pain and complications in highly symptomatic gallstone
patients scheduled for cholecystectomy. We also evaluated potential beneficial effects of
impaired gallbladder motility

Study Phase

Phase 4

Study Type

Interventional

Primary Outcome

incidence severe right upper quadrant or midline epigastric pain (> 30 min)and colic-free intervals

Secondary Outcome

 nr gallstone complications (acute cholecystitis, choledocholithiasis or acute pancreatitis) and non-severe right upper quadrant or midline epigastric pain and nr aalgesics taken

Condition

Cholecystolithiasis

Intervention

ursodeoxycholic acid

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

November 2001

Completion Date

November 2004

Eligibility Criteria

        Inclusion Criteria:

          -  Patients between 18 and 75 years of age study are upon admission to the waiting list
             for elective cholecystectomy for symptomatic cholecystolithiasis defined as:

               -  presence of gallbladder stones or sludge, without bile duct stones or bile duct
                  dilatation at ultrasonography;\

               -  at least one episode of severe right upper quadrant or midline epigastric pain of
                  at least 30 min. duration, with radiation and/or movement urge, or at least three
                  episodes of severe right upper quadrant or midline epigastric pain of at least 30
                  min. duration without such radiation or movement urge, in the previous 12 months

        Exclusion Criteria:

          -  Contra-indication for general anaesthesia or surgery

          -  Current or previous acute cholecystitis, obstructive jaundice or pancreatitis

          -  Previous papillotomy, because of preferential flow of UDCA-enriched bile to the
             intestine rather than to the gallbladder

          -  Pregnancy or lactation

          -  Current or previous use of UDCA

          -  Participation in another study

          -  Inability to speak Dutch or English or mental disability

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Niels G Venneman, MD, ,

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations

NCT ID

NCT00161083

Organization ID

MLDS WS 00-08

Secondary IDs

MLDS WS 00-08

Study Sponsor

UMC Utrecht

Collaborators

 Dr. Falk Pharma GmbH

Study Sponsor

Niels G Venneman, MD, Principal Investigator, UMC Utrecht

Verification Date

September 2005