Alagille Syndrome Clinical Trial
Official title:
The Safety and Efficacy of Atorvastatin on Xanthoma in Alagille Syndrome
To observe the efficacy and safety of atorvastatin on xanthoma in Alagille syndrome through a prospective study.
Status | Recruiting |
Enrollment | 10 |
Est. completion date | March 22, 2025 |
Est. primary completion date | March 22, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Day to 17 Years |
Eligibility | Inclusion Criteria: - Meet the ALGS diagnostic criteria; - Xanthoma of skin; - Before treatment with atorvastatin,non-HDL-C=5.76mmol/L(223 mg/dL); - Informed consent; - Age 0-17 years old, male or female; - Taking bile acid chelator (colenemide) has no obvious effect or intolerance. Exclusion Criteria: - Liver transplantation has been performed; - In the recovery period of cholestasis, xanthoma is obviously subsiding; - Patients with serious systemic diseases and unstable vital signs; - Progressive active liver injury, such as continuous increase of transaminase; - Serious myopathy; - Known to be allergic to any component of atorvastatin; - The weight is less than 5kg. |
Country | Name | City | State |
---|---|---|---|
China | Children's Hospital of Fudan University | Shanghai | Shanghai |
Lead Sponsor | Collaborator |
---|---|
Children's Hospital of Fudan University |
China,
Agrawal D, Manchanda SC, Sawhney JPS, Kandpal B, Jain R, Mehta A, Mohanty A, Passey R, Makhija A, Sharma MK. To study the effect of high dose Atorvastatin 40mg versus 80mg in patients with dyslipidemia. Indian Heart J. 2018 Dec;70 Suppl 3(Suppl 3):S8-S12. doi: 10.1016/j.ihj.2018.01.034. Epub 2018 Jan 31. — View Citation
Araujo MB, Pacce MS. A 10-year experience using combined lipid-lowering pharmacotherapy in children and adolescents. J Pediatr Endocrinol Metab. 2016 Nov 1;29(11):1285-1291. doi: 10.1515/jpem-2016-0117. — View Citation
Ben Ameur S, Chabchoub I, Telmoudi J, Belfitouri Y, Rebah O, Lacaille F, Aloulou H, Mehrzi A, Hachicha M. Management of cholestatic pruritus in children with Alagille syndrome: Case report and literature review. Arch Pediatr. 2016 Dec;23(12):1247-1250. doi: 10.1016/j.arcped.2016.09.004. Epub 2016 Oct 27. — View Citation
Gandelman K, Glue P, Laskey R, Jones J, LaBadie R, Ose L. An eight-week trial investigating the efficacy and tolerability of atorvastatin for children and adolescents with heterozygous familial hypercholesterolemia. Pediatr Cardiol. 2011 Apr;32(4):433-41. doi: 10.1007/s00246-011-9885-z. Epub 2011 Jan 23. — View Citation
Gilbert MA, Bauer RC, Rajagopalan R, Grochowski CM, Chao G, McEldrew D, Nassur JA, Rand EB, Krock BL, Kamath BM, Krantz ID, Piccoli DA, Loomes KM, Spinner NB. Alagille syndrome mutation update: Comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification. Hum Mutat. 2019 Dec;40(12):2197-2220. doi: 10.1002/humu.23879. Epub 2019 Aug 26. — View Citation
Hari P, Khandelwal P, Satpathy A, Hari S, Thergaonkar R, Lakshmy R, Sinha A, Bagga A. Effect of atorvastatin on dyslipidemia and carotid intima-media thickness in children with refractory nephrotic syndrome: a randomized controlled trial. Pediatr Nephrol. 2018 Dec;33(12):2299-2309. doi: 10.1007/s00467-018-4036-x. Epub 2018 Aug 8. — View Citation
Huang J, Li L, Zhang J, Gao C, Quan W, Tian Y, Sun J, Tian Q, Wang D, Dong J, Zhang J, Jiang R. Treatment of Relapsed Chronic Subdural Hematoma in Four Young Children with Atorvastatin and Low-dose Dexamethasone. Pharmacotherapy. 2019 Jul;39(7):783-789. doi: 10.1002/phar.2276. Epub 2019 May 28. — View Citation
Kakaei F, Nikeghbalian S, Kazemi K, Salahi H, Bahador A, Dehghani SM, Dehghani M, Nejatollahi SM, Shamsaeefar A, Khosravi MB, Malek-Hosseini SA. Liver transplantation for homozygous familial hypercholesterolemia: two case reports. Transplant Proc. 2009 Sep;41(7):2939-41. doi: 10.1016/j.transproceed.2009.07.028. — View Citation
Langslet G, Breazna A, Drogari E. A 3-year study of atorvastatin in children and adolescents with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2016 Sep-Oct;10(5):1153-1162.e3. doi: 10.1016/j.jacl.2016.05.010. Epub 2016 Jun 7. — View Citation
Larrosa-Haro A, Saenz-Rivera C, Gonzalez-Ortiz M, Coello-Ramirez P, Vazquez-Camacho G. Lack of cholesterol-lowering effect of graded doses of cholestyramine in children with Alagille syndrome: a pilot study. J Pediatr Gastroenterol Nutr. 2003 Jan;36(1):50-3. doi: 10.1097/00005176-200301000-00011. — View Citation
Lin M, Dai H, Zhao S. Long-term atorvastatin-ezetimibe-probucol triple therapy for homozygous familial hypercholesterolaemia from early childhood. Cardiol Young. 2016 Jan;26(1):197-201. doi: 10.1017/S1047951115000591. Epub 2015 Apr 24. — View Citation
Luirink IK, Hutten BA, Greber-Platzer S, Kolovou GD, Dann EJ, de Ferranti SD, Taylan C, Bruckert E, Saheb S, Oh J, Driemeyer J, Farnier M, Pape L, Schmitt CP, Novoa FJ, Maeser M, Masana L, Shahrani A, Wiegman A, Groothoff JW. Practice of lipoprotein apheresis and short-term efficacy in children with homozygous familial hypercholesterolemia: Data from an international registry. Atherosclerosis. 2020 Apr;299:24-31. doi: 10.1016/j.atherosclerosis.2020.01.031. Epub 2020 Feb 18. — View Citation
Martinsen MH, Klausen IC, Tybjaerg-Hansen A, Hedegaard BS. Autosomal recessive hypercholesterolemia in a kindred of Syrian ancestry. J Clin Lipidol. 2020 Jul-Aug;14(4):419-424. doi: 10.1016/j.jacl.2020.06.002. Epub 2020 Jun 8. — View Citation
Melvin AJ, Montepiedra G, Aaron L, Meyer WA 3rd, Spiegel HM, Borkowsky W, Abzug MJ, Best BM, Crain MJ, Borum PR, Graham B, Anthony P, Shin K, Siberry GK; P1063 Study Team. Safety and Efficacy of Atorvastatin in Human Immunodeficiency Virus-infected Children, Adolescents and Young Adults With Hyperlipidemia. Pediatr Infect Dis J. 2017 Jan;36(1):53-60. doi: 10.1097/INF.0000000000001352. — View Citation
Nakajima H, Tsuma Y, Fukuhara S, Kodo K. A Case of Infantile Alagille Syndrome With Severe Dyslipidemia: New Insight into Lipid Metabolism and Therapeutics. J Endocr Soc. 2022 Jan 18;6(3):bvac005. doi: 10.1210/jendso/bvac005. eCollection 2022 Mar 1. — View Citation
Niedra E, Chahal N, Manlhiot C, Yeung RS, McCrindle BW. Atorvastatin safety in Kawasaki disease patients with coronary artery aneurysms. Pediatr Cardiol. 2014 Jan;35(1):89-92. doi: 10.1007/s00246-013-0746-9. Epub 2013 Jul 18. — View Citation
Quek SC, Aw M, Quak SH, Prabhakaran K, Tan KC. Liver transplantation in a child with severe hypercholesterolaemia in Alagille syndrome. Ann Acad Med Singap. 2001 Jan;30(1):44-7. — View Citation
Sheflin-Findling S, Arnon R, Lee S, Chu J, Henderling F, Kerkar N, Iyer K. Partial internal biliary diversion for Alagille syndrome: case report and review of the literature. J Pediatr Surg. 2012 Jul;47(7):1453-6. doi: 10.1016/j.jpedsurg.2012.04.008. — View Citation
Shurberg JL, Resnick RH, Koff RS, Ros E, Baum RA, Pallotta JA. Serum lipids, insulin, and glucagon after portacaval shunt in cirrhosis. Gastroenterology. 1977 Feb;72(2):301-4. — View Citation
Sreedharan AV, Pek SLT, Tan TH, Tavintharan S, Yap F. Successful pharmacological management of a child with compound heterozygous familial hypercholesterolemia and review of the recent literature. J Clin Lipidol. 2020 Sep-Oct;14(5):639-645. doi: 10.1016/j.jacl.2020.07.006. Epub 2020 Jul 15. — View Citation
Tapia Ceballos L, Picazo Angelin B, Ruiz Garcia C. [Use of statins in children]. An Pediatr (Barc). 2008 Apr;68(4):385-92. doi: 10.1157/13117712. Spanish. — View Citation
Tremoulet AH, Jain S, Jone PN, Best BM, Duxbury EH, Franco A, Printz B, Dominguez SR, Heizer H, Anderson MS, Glode MP, He F, Padilla RL, Shimizu C, Bainto E, Pancheri J, Cohen HJ, Whitin JC, Burns JC. Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm. J Pediatr. 2019 Dec;215:107-117.e12. doi: 10.1016/j.jpeds.2019.07.064. Epub 2019 Sep 24. — View Citation
* Note: There are 22 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Grade change of xanthoma | The grade change of xanthoma would be assessed at the 3th/6th month after enrollment ?Explanation:Xanthomas were graded as 0 = none, 1 = minimal, 2 =moderate, 3 = disfiguring, and 4 = disabling. Minimal xanthomas signified fewer than 20 scattered individual lesions, moderate represented more than 20 lesions that did not interfere with or limit activities, disfiguring represented large numbers of lesions that by their large numbers or size caused distortion of the face or xtremities, and disabling signified that the xanthomas interfered with function (such as hand use or ability to walk) because of excess size or number.? | from enrollment to the 3th/6th month | |
Secondary | non-HDL-C change | The non-HDL-C change would be measured at the 3th/6th month after enrollment ?Explanation: non-HDL-C is defined as the difference between total cholesterol and HDL-C? | from enrollment to the 3th/6th month | |
Secondary | Incidence of adverse events | It is a binary variable. Incidence Rates for adverse event(including:rhabdomyolysis and myopathy,liver enzymes exceeded twice the baseline value,nasopharyngitis, muscle pain,diarrhea,nausea, fever,urinary tract infection, joint swelling,epistaxis,urticaria,etc.)would be calculated. | from enrollment to the 3th/6th month |
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