BAT117213: Ileal bile acid transporter (IBAT) inhibition as a treatment for pruritus in primary biliary cirrhosis: Study protocol for a randomised controlled trial

BMC Gastroenterology

Volumn 16, Issue 1, 2016, Pages

  Hegade, Vinod S ^a   Kendrick, Stuart F W ^a,b   Dobbins, Robert L ^c   Miller, Sam R ^b   Richards, Duncan ^b   Storey, James ^b   Dukes, George ^c   Gilchrist, Kim ^c   Vallow, Susan ^c   Alexander, Graeme J ^d   Corrigan, Margaret ^e   Hirschfield, Gideon M ^d   Jones, David E J ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

^c GLAXOSMITHKLINE   (United States)

^d CAMBRIDGE UNIVERSITY HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^e University Hospitals Birmingham NHS Foundation Trust   (United Kingdom)

Author keywords

IBAT; Ileal bile acid transporter; PBC; Primary biliary cholangitis; Pruritus

Indexed keywords

BILE ACID; BILE ACID SEQUESTRANT; CARRIER PROTEINS AND BINDING PROTEINS; GSK 2330672; ILEAL BILE ACID TRANSPORTER; PLACEBO; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID; 3-((((3R,5R)-3-BUTYL-3-ETHYL-7-(METHYLOXY)-1,1-DIOXIDO-5-PHENYL-2,3,4,5-TETRAHYDRO-1,4-BENZOTHIAZEPIN-8-YL)METHYL)AMINO)PENTANEDIOIC ACID; BIOLOGICAL MARKER; CHOLAGOGUE; COTRANSPORTER; METHYLAMINE; ORGANIC ANION TRANSPORTER; SODIUM-BILE ACID COTRANSPORTER; THIAZEPINE DERIVATIVE;

ADULT; AGED; ARTICLE; BILE ACID BLOOD LEVEL; BILE ACID SYNTHESIS; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PHASE 2 CLINICAL TRIAL; PRIMARY BILIARY CIRRHOSIS; PRURITUS; RANDOMIZED CONTROLLED TRIAL; REPEATED DRUG DOSE; STEADY STATE; TREATMENT DURATION; TREATMENT OUTCOME; ADOLESCENT; ANTAGONISTS AND INHIBITORS; BILIARY CIRRHOSIS; BLOOD; CLINICAL TRIAL; COMBINATION DRUG THERAPY; COMPLICATION; MIDDLE AGED; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; BILE ACIDS AND SALTS; BIOMARKERS; CHOLAGOGUES AND CHOLERETICS; CROSS-OVER STUDIES; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; LIVER CIRRHOSIS, BILIARY; MALE; METHYLAMINES; MIDDLE AGED; ORGANIC ANION TRANSPORTERS, SODIUM-DEPENDENT; PRURITUS; SYMPORTERS; THIAZEPINES; URSODEOXYCHOLIC ACID; YOUNG ADULT;

EID: 84978719084     PISSN: None     EISSN: 1471230X     Source Type: Journal    
DOI: 10.1186/s12876-016-0481-9     Document Type: Article

References (31)

1. Griffiths L, Dyson JK, Jones DE. The new epidemiology of primary biliary cirrhosis. Semin Liver Dis. 2014;34(3):318-28. doi: 10.1055/s-0034-1383730. published Online First: Epub Date.
2. Beuers U, Boberg KM, Chapman RW, et al. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-67. doi: 10.1016/j.jhep.2009.04.009. published Online First: Epub Date.
3. Hegade VS, Mells GF, Beuers U, et al. Patient Experience and Characteristics of Cholestatic Pruritus in the UK-PBC Research Cohort. Hepatology. 2014;60:339A-69. doi: 10.1002/hep.27496. published Online First: Epub Date.
4. Hegade VS, Mells GF, Lammert C, et al. A Comparative Study of Pruritus in PBC cohorts from UK, USA and Italy. J Hepatol. 2015;62:S785.
5. Mells GF, Pells G, Newton JL, et al. Impact of primary biliary cirrhosis on perceived quality of life: the UK-PBC national study. Hepatology. 2013;58(1):273-83. doi: 10.1002/hep.26365. published Online First: Epub Date.
6. Lindor KD, Gershwin ME, Poupon R, et al. Primary biliary cirrhosis. Hepatology. 2009;50(1):291-308. doi: 10.1002/hep.22906. published Online First: Epub Date.
7. Dyson JK, Webb G, Hirschfield GM, et al. Unmet clinical need in autoimmune liver diseases. J Hepatol. 2015;62(1):208-18. doi: 10.1016/j.jhep.2014.09.010. published Online First: Epub Date.
8. Dawson PA, Haywood J, Craddock AL, et al. Targeted deletion of the ileal bile acid transporter eliminates enterohepatic cycling of bile acids in mice. J Biol Chem. 2003;278(36):33920-7. doi: 10.1074/jbc.M306370200. published Online First: Epub Date.
9. Lanzini A, De Tavonatti MG, Panarotto B, et al. Intestinal absorption of the bile acid analogue 75Se-homocholic acid-taurine is increased in primary biliary cirrhosis, and reverts to normal during ursodeoxycholic acid administration. Gut. 2003;52(9):1371-5.
10. Hegade VS, Krawczyk M, Kremer AE, et al. The safety and efficacy of nasobiliary drainage in the treatment of refractory cholestatic pruritus: a multicentre European study. Aliment Pharmacol Ther. 2016;43(2):294-302. doi: 10.1111/apt.13449. published Online First: Epub Date.
11. Neuberger J, Jones EA. Liver transplantation for intractable pruritus is contraindicated before an adequate trial of opiate antagonist therapy. Eur J Gastroenterol Hepatol. 2001;13(11):1393-4.
12. Wong MH, Oelkers P, Dawson PA. Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. J Biol Chem. 1995;270(45):27228-34.
13. Baghdasaryan A, Fuchs CD, Osterreicher CH, et al. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis. J Hepatol. 2016;64(3):674-81. doi: 10.1016/j.jhep.2015.10.024. published Online First: Epub Date.
14. Graffner H, Gillberg PG, Rikner L, Marschall HU. The ileal bile acid transporter inhibitor A4250 decreases serum bile acids by interrupting the enterohepatic circulation. Aliment Pharmacol Ther. 2016;43(2):303-10. doi: 10.1111/apt.13457. published Online First: Epub Date.
15. Jopson L, Newton JL, Palmer J, et al. RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial. BMJ Open. 2015;5(8):e007985. doi: 10.1136/bmjopen-2015-007985. published Online First: Epub Date.
16. Jacoby A, Rannard A, Buck D, et al. Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis. Gut. 2005;54(11):1622-9. doi: 10.1136/gut.2005.065862. published Online First: Epub Date.
17. Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. 2010;162(3):587-93. doi: 10.1111/j.1365-2133.2009.09586.x. published Online First: Epub Date.
18. Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int. 2006;26(8):943-8. doi: 10.1111/j.1478-3231.2006.01326.x. published Online First: Epub Date.
19. Tandon P, Rowe BH, Vandermeer B, Bain VG. The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol. 2007;102(7):1528-36. doi: 10.1111/j.1572-0241.2007.01200.x. published Online First: Epub Date.
20. Datta DV, Sherlock S. Cholestyramine for long term relief of the pruritus complicating intrahepatic cholestasis. Gastroenterology. 1966;50(3):323-32.
21. Oster ZH, Rachmilewitz EA, Moran E, Stein Y. Relief of pruritus by cholestyramine in chronic liver disease. Isr J Med Sci. 1965;1(4):599-606.
22. Datta DV, Sherlock S. Treatment of pruritus of obstructive jaundice with cholestyramine. Br Med J. 1963;1(5325):216-9.
23. Van Itallie TB, Hashim SA, Crampton RS, Tennent DM. The treatment of pruritus and hypercholesteremia of primary biliary cirrhosis with cholestyramine. N Engl J Med. 1961;265:469-74. doi: 10.1056/NEJM196109072651004. published Online First: Epub Date.
24. Carey Jr JB, Williams G. Relief of the pruritus of jaundice with a bile-acid sequestering resin. JAMA. 1961;176:432-5.
25. Terg R, Coronel E, Sorda J, Munoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study. J Hepatol. 2002;37(6):717-22.
26. Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Van Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology. 1997;113(4):1264-9.
27. Ghent CN, Carruthers SG. Treatment of pruritus in primary biliary cirrhosis with rifampin. Results of a double-blind, crossover, randomized trial. Gastroenterology. 1988;94(2):488-93.
28. Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology. 2007;45(3):666-74. doi: 10.1002/hep.21553. published Online First: Epub Date.
29. Bergasa NV, McGee M, Ginsburg IH, Engler D. Gabapentin in patients with the pruritus of cholestasis: a double-blind, randomized, placebo-controlled trial. Hepatology. 2006;44(5):1317-23. doi: 10.1002/hep.21370. published Online First: Epub Date.
30. Kuiper EM, van Erpecum KJ, Beuers U, et al. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52(4):1334-40. doi: 10.1002/hep.23821. published Online First: Epub Date.
31. Hegade VS, Kendrick SF, Jones DE. Drug treatment of pruritus in liver diseases. Clin Med. 2015;15(4):351-7. doi: 10.7861/clinmedicine.15-4-351. published Online First: Epub Date.