None listed
Conditions
Brief summary
Low Phospholipid Associated Cholelithiasis (LPAC) is a cause of post-operative pain and recurrent gallstones after gallbladder removal (cholecystectomy). This is a randomised control trial of a medication called ursodeoxycholic acid in patients with LPAC to prevent pain post gallbladder surgery, improve quality of life, reduce hospital presentations and patient use of strong narcotic painkillers. This trial is a crossover trial where participants will be randomised to undergo a 1 year experimental (ursodeoxycholic acid) or control arm (placebo). The experimental or control arm will be prescribed a daily dose of 10mg/kg of ursodeoxycholic acid or placebo. Participants will then undergo a 2 week washout period before crossing over to the opposite arm to complete the study. The dose will be prescribed at 10mg/kg daily and can be titrated to a maximum of 20mg/kg daily at the discretion of the treating clinician. The primary study outcome is number of episodes of biliary pain. Secondary outcomes include quality of life, hospitalisations, liver ultrasound findings.
Interventions
Ursodeoxycholic acid capsules orally starting at 10mg/kg daily with the ability to be increased to a maximum of 20mg/kg daily at the treating clinician's discretion if the participant is continuing to experience biliary pain. In the event of diarrhoea, ursodeoxycholic acid can be down titrated to 5mg/kg and slowly increased as tolerated. Cross-over trial design. Duration is for 1 year (52 weeks) each for ursodeoxycholic acid and placebo. The wash out period is 2 weeks. Adherence is monitored by
Ursodeoxycholic acid capsules orally starting at 10mg/kg daily with the ability to be increased to a maximum of 20mg/kg daily at the treating clinician's discretion if the participant is continuing to experience biliary pain. In the event of diarrhoea, ursodeoxycholic acid can be down titrated to 5mg/kg and slowly increased as tolerated. Cross-over trial design. Duration is for 1 year (52 weeks) each for ursodeoxycholic acid and placebo. The wash out period is 2 weeks. Adherence is monitored by the Clinical Trials Pharmacy Department who will monitor unused capsules.
Sponsors
Melbourne Health
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1) Patients aged greater than 18 years with a previous cholecystectomy with more than 2 episodes of biliary pain in the last 12 months. Characteristics of biliary pain as defined by the Rome IV criteria: • Pain located in the epigastrium and/or right upper quadrant and all of the following: o 1. Builds up to a steady level and lasting 30 minutes or longer. o 2. Occurring at different intervals (not daily). o 3. Severe enough to interrupt daily activities or lead to an emergency department visit. o 4. Not significantly (<20%) related to bowel movements. o 5. Not significantly (<20%) relieved by postural change or acid suppression. Supportive Criteria The pain may be associated with: o 1. Nausea and vomiting. o 2. Radiation to the back and/or right infrasubscapular region. o 3. Waking from sleep. 2) At least 2 additional features of: a) Age less than 40 years at onset of biliary symptoms. b) Imaging features consistent with LPAC: o Intrahepatic echogenic foci in a position consistent with biliary tree, with either comet tail artefact, acoustic shadowing, or twinkle artefact. Echoes that have an appearance consistent with biliary gas will not qualify under this inclusion definition. o Intrahepatic gallstones evidenced by US, CT, including CT-intravenous cholangiography, direct cholangiography, or MRCP. o Intrahepatic strictures and dilatation typical of LPAC c) Familial history of cholecystectomy in first-degree relatives age <40 years d) Evidence of transiently abnormal liver function tests corresponding with episodes of biliary pain
Exclusion criteria
• Stone in the common bile duct on imaging. • Known history of primary sclerosing cholangitis, primary biliary cholangitis, colitis, Crohn’s disease, cystic fibrosis, chronic liver disease. • Presence of significant psychiatric disorders: o Lifetime psychotic disorders, bipolar disorder; o Substance use disorders within 6 months; o Eating disorders within 2 years; o Moderate & severe depression defined BDI cutoff scores >22 (unless receiving stable psychiatric therapy for six weeks); and/or, o Suicidal risk - a score of greater than 0 on question 9 of the BDI. • Pregnancy: Women who are pregnant or are planning a pregnancy within 2 years at the time of screening will be excluded from the study. • Upper endoscopy examination with significant findings to explain the pain. • Any functional bowel disorders. • Cholecystectomy less than 90 days before enrollment. • Any use of regular narcotics. • Inability to comply with study procedures and agents. • Any significant medical illness that would interfere with study participation. • Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation.
Outcome results
None listed