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Atorvastatin Therapy on Xanthoma in Alagille Syndrome

Sponsor
Children's Hospital of Fudan University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05488067
Collaborator
(none)
10
Enrollment
1
Location
1
Arm
36
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To observe the efficacy and safety of atorvastatin on xanthoma in Alagille syndrome through a prospective study.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Alagille syndrome (ALGS, OMIM 118450) is an important cause of chronic cholestasis in children, and the incidence rate is about 1:30000~1:50000. Most patients with ALGS have hypercholesterolemia. In severe cases, multiple xanthomas can be seen, and some patients are accompanied by severe itching and pain. Disfigured xanthomas affect the normal social interaction of patients, thereby causing physical and mental damage to children. At present, xanthoma caused by hypercholesterolemia can be cured by treating the primary disease, taking lipid-lowering drugs (such as bile acid chelators, ezetimibe, statins, etc.), or lipoprotein apheresis. If it affects the beauty or function, local treatment such as 33% trichloroacetic acid dot coating, carbon dioxide laser, liquid nitrogen freezing or surgical resection is feasible, and even surgical operation( such as portal vena cava anastomosis, liver transplantation). Compared with expensive lipoprotein apheresis and other invasive therapies, taking lipid-lowering drug has the advantages of higher acceptance, lower cost and higher safety. However, at present, there are no guidelines for application of oral lipid-lowering drugs in children under 6 years old with hypercholesterolemia. Therefore, the purpose of this study is to clarify the safety and efficacy of atorvastatin on xanthoma in ALGS , so as to provide reference for the treatment of ALGS patients' xanthomas.

Risk prevention and treatment: The patients began to take atorvastatin from a small dose, followed up closely in the early stage (2-4 weeks) to see if the patients had obvious discomfort such as myalgia, and monitored the changes of Biochemistry (CK, ALT, AST, etc.). If moderate or more serious adverse reactions occurred during the trial or the following laboratory abnormalities occurred (CK exceeded 10 times the upper limit of normal; ALT or AST had been continued to rise, exceeding 2 times the baseline value), atorvastatin was temporarily stopped, and patients should be rechecked within 2 weeks. It is necessary to reevaluate and decide whether to restart atorvastatin treatment.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Safety and Efficacy of Atorvastatin on Xanthoma in Alagille Syndrome
Actual Study Start Date :
Mar 22, 2022
Anticipated Primary Completion Date :
Mar 22, 2025
Anticipated Study Completion Date :
Mar 22, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Atorvastatin+ALGS-Xanthoma

Drug: atorvastatin Dosage form: tablet Route of administration: oral Duration: about 3 months~1year Administration method: Initial dose: ① < 1 year old: 0.25mg/kg/d, qd; ② 1-5 years old: 2.5mg/d, qd; ③ 6-9 years old: 5mg/d, qd; ④ ≥ 10 years old: 10mg/d, qd. The maximum dose is 40mg/d or 1mg/kg/d. During the follow-up, the medication was adjusted according to the laboratory results until LDL-C ≤ 3.5 mmol/l (135 mg/dl), xanthoma disappear, or the patient had moderate or more serious adverse reactions.

Drug: atorvastatin
Oral atorvastatin treatment for ALGS children with xanthoma
Other Names:
  • Lipitor

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Grade change of xanthoma [from enrollment to the 3th/6th month]

      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.】

    Secondary Outcome Measures

    1. LDL-C change [from enrollment to the 3th/6th month]

      The LDL-C change would be measured at the 3th/6th month after enrollment

    2. Incidence of adverse events [from enrollment to the 3th/6th month]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Day to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Meet the ALGS diagnostic criteria;

    • Xanthoma of skin; ③ Before treatment with atorvastatin, LDL-C≥4.9mmol/L（190 mg/dL）； ④ Informed consent; ⑤ 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;

    ④ Progressive active liver injury, such as continuous increase of transaminase;

    • Serious myopathy;

    ⑥ Known to be allergic to any component of atorvastatin.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital of Fudan University Shanghai Shanghai China 201102

    Sponsors and Collaborators

    • Children's Hospital of Fudan University

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Children's Hospital of Fudan University
    ClinicalTrials.gov Identifier:
    NCT05488067
    Other Study ID Numbers:
    • ATO-ALGS-XAN
    First Posted:
    Aug 4, 2022
    Last Update Posted:
    Aug 4, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Alagille Syndrome
    Xanthomatosis
    Syndrome
    Atorvastatin

    Study Results

    No Results Posted as of Aug 4, 2022