The Role of Ursodeoxycholic Acid in Treatment of Gallstones in Hemolytic Disorders

NCT02472509 | Terminated Phase 4

• 1 other identifier: Ursolit_Hemolytic disorders
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

It is well established that hemolytic diseases predispose patients to the development of pigment gallstones. Gallstones are noted in at least 5% of children under the age of 10 years, increasing to 40-50% in the second to fifth decades. The co-inheritance of Gilbert's syndrome increases the risk of cholelithiasis four to five-fold. In patients with chronic hemolysis, total bile lipid concentration is decreased and the total bilirubin to total lipid ratio is increased. This suggests that the conjugating capacity of hepatocytes is surpassed by the excessive amount of bilirubin resulting from hemolysis. Increased bilirubin monoconjugate and unconjugated bilirubin can precipitate in bile and form complexes with inorganic ions, mostly calcium, and develop into stones. Patients with hemolytic disorders can also develop biliary sludge, a suspension of precipitated particulate matter in bile dispersed in a viscous, mucin-rich liquid phase . The chemical composition of the precipitates correlates well with the composition of the associated stone and sludge often stands as a harbinger of future stone development. There is strong data suggesting a benefit in treating cholelithiasis with UDCA and also in preventing gallstone development in various high risk scenarios. There are several proposed mechanisms for the positive effect of UDCA in primary prevention of pigment stones. Mucoglycoproteins are present in significant amounts in black pigment stones and contribute to the matrix of gallstones. UDCA suppresses the secretion of protein and decreases the levels of various proteins in bile . It has also been suggested that increased colonic bile salt may solubilize unconjugated bilirubin and may prevent calcium complexing. There is no published data at present on the role of UDCA in prevention and treatment of cholelithiasis in hemolytic diseases. The investigators hypothesise that UDCA can be of benefit to patients with hemolytic disorders in the primary prevention of pigment stones, possible resolution of biliary sludge and existent stones, and reduction of symptomatic episodes of cholelithiasis.

Conditions

Hemolytic Disorders; Gallstones

Keywords

Ursodeoxycholic acid (UDCA); White blood cells (WBC); Alanine Transaminase (ALT); Alkaline Phosphatase (ALP); Aspartate Aminotransferase (AST); Gamma-Glutamyl Transpeptidase (GGT); Lactate dehydrogenase (LDH); Low-Density Lipoprotein (LDL); High-Density Lipoprotein (HDL); Glucose-6-phosphate dehydrogenase (G6PD); Ultrasound (US)

Outcome Measures

Primary Outcomes (1)

• Lack of sonographic, clinical or biochemical evidence of progression of cholelithiasis or biliary sludge.

  12 months

Secondary Outcomes (5)

• Improvement in number and severity of episodes of symptomatic gallstones.

  12 months

• Rate of surgical intervention for gallstones disease.

  12 months

• Sonographic improvement (size and number of gallstones, presence of bile sludge, gallbladder wall thickness).

  12 months

• Evaluate tolerability and adverse effects of UDCA therapy in hemolytic disorders.

  12 months

• Improved biochemical evidence of gallstone disease

  12m

Study Arms (1)

Open Label

EXPERIMENTAL

32 patients with hemolytic disorders meeting the inclusion and exclusion criteria will be commenced on Ursodeoxycholic acid (UDCA).

Drug: Ursodeoxycholic Acid

Interventions

Ursodeoxycholic Acid DRUG

Patients will be commenced on UDCA 15mg/kg/day (maximum dose 900mg/day) in 2-3 divided doses for 12 months. Patients who are unable to tolerate tablet medication will be started on UDCA syrup at the same dose.

Also known as: Ursolit

Open Label

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of a hemolytic disorder including spherocytosis, G6PD deficiency, thalassemia or sickle cell disease.
• Patients with cholelithiasis or bile sludge.
• Age greater than or equal to 4 years.
• Ability to consent to and participate in the study and follow study procedures.

You may not qualify if:

• Previous splenectomy (complete or partial)
• Evidence of hemolytic crisis at the time of research enrollment
• Patients with highly symptomatic gallstones who have planned surgical intervention
• Known allergy or intolerance to UDCA
• Existence of concurrent hepatic disease
• Any other laboratory or clinical condition that the investigator considers clinically significant that could impact the outcome of the study or the safety of the patient.

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead

Study Sites (1)

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

MeSH Terms

Conditions

Gallstones

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Cholelithiasis; Biliary Tract Diseases; Digestive System Diseases; Cholecystolithiasis; Gallbladder Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Oren Ledder, MD

  Shaare Zedek Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2015
• First Posted: June 16, 2015
• Study Start: December 1, 2014
• Primary Completion: September 10, 2017
• Study Completion: September 10, 2017
• Last Updated: October 10, 2017

Record last verified: 2017-10

Locations

IL (1)