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Recruiting NCT04532346

Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes

Early Phase I Interventional Interstitial Lung Disease Surfactant Dysfunction

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Hydroxychloroquine.
Who it may be relevant to
Registry conditions: Interstitial Lung Disease, Surfactant Dysfunction. Basic parameters: 1 months — 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Safety and Efficacy of Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes: a Randomized Controlled Study

Overview

The aim of this proposed study is to evaluate the efficacy and safety of hydroxychloroquine (HCQ) in children's interstitial lung diseases(chILD) with genetic causes. This study is a randomized controlled clinical trial.

Detailed description

Children Interstitial lung disease (chILD) is a heterogeneous group of rare respiratory disorders of known and unknown etiologies that are mostly chronic and associated with high morbidity and mortality. Genetic factors are important contributors to chILD. Genetic variations have been mainly described in genes encoding (or interacting with) the surfactant proteins (SP): SP-C (SFTPC) and the ATP-binding cassette-family A-member 3 (ABCA3) (ABCA3), and less frequently in the genes encoding NKX homeobox 2 (NKX2)-1 (NKX2-1), SP-B (SFTPB), SP-A (SFTPA) and other genes.

Hydroxychloroquine has been reported to be useful in cases or case series of chILD including those with genetic causes alone or in combination with systemic steroids. However, the efficacy is highly variable and no randomized controlled study has been reported. The study is a randomized controlled investigation aiming to evaluate the efficacy and safety of hydroxychloroquine in chILD with genetic causes.

Interventions

  • Drug Hydroxychloroquine
    Hydroxychloroquine Sulfate is an anti-malarial and anti-rheumatic drug. hydroxychloroquine has been reported to improve the clinical status of chILD cases wtih genetic causes. The exact mechanism of action of hydroxychloroquine is unknown. In additon to having anti-inflammatory properties, hydroxychloroquine has been shown to affect intracellular processing of surfactant protein.

Primary outcome measures

  • Oxygenation status [Time frame: at first month, at 3rd month, at 6th month, at 12th month]
Secondary outcome measures (1)
  • Improvement in clinical manifestation [Time frame: at first month, at 3rd month, at 6th month, at 12th month]

Eligibility criteria

Inclusion criteria

  • A clinical diagnosis of chILD with age<18 years
  • Genetically diagnosed (e.g. SFTPC, SFTPB, ABCA3, NKX2-1, CSF2RA, CSF2RB, IARS, MARS, COPA, SLC7A7, LRBA)
  • Patients have to be clinically stable with no major changes in their medication in the last 4 weeks
  • No HCQ treatment in the last 12 weeks
  • Signed and dated informed consent of the subject (if subject has the ability) and the representatives (of underaged children) must be available before start of any specific trial procedures

Exclusion criteria

  • Acute severe infectious exacerbations
  • Known hypersensitivity to HCQ, or other ingredients of the tablets
  • Proven retinopathy or maculopathy
  • Renal insufficiency at screening, defined as glomerular filtration rate (GFR)< 40 mL/min/1.73 m2 in patients aged 3 to 8 weeks< 60 mL/min/1.73 m2 in patients ≥ 8 weeks of age
  • Participation in other clinical trials during the present clinical trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

China · 1 center
  • Children's hospital of Fudan University — Shanghai

Publications

  • Kurland G, Deterding RR, Hagood JS, Young LR, Brody AS, Castile RG, Dell S, Fan LL, Hamvas A, Hilman BC, Langston C, Nogee LM, Redding GJ; American Thoracic Society Committee on Childhood Interstitial Lung Disease (chILD) and the chILD Research Network. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disea PMID 23905526
  • Bush A, Cunningham S, de Blic J, Barbato A, Clement A, Epaud R, Hengst M, Kiper N, Nicholson AG, Wetzke M, Snijders D, Schwerk N, Griese M; chILD-EU Collaboration. European protocols for the diagnosis and initial treatment of interstitial lung disease in children. Thorax. 2015 Nov;70(11):1078-84. doi: 10.1136/thoraxjnl-2015-207349. Epub 2015 Jul 1. PMID 26135832
  • Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean JA, Brody AS, Nogee LM, Trapnell BC, Langston C; Pathology Cooperative Group; Albright EA, Askin FB, Baker P, Chou PM, Cool CM, Coventry SC, Cutz E, Davis MM, Dishop MK, Galambos C, Patterson K, Travis WD, Wert SE, White FV; ChILD Research Co-operative. Diffuse lung disease in young children: application of a novel classification scheme. Am PMID 17885266
  • Litao MK, Hayes D Jr, Chiwane S, Nogee LM, Kurland G, Guglani L. A novel surfactant protein C gene mutation associated with progressive respiratory failure in infancy. Pediatr Pulmonol. 2017 Jan;52(1):57-68. doi: 10.1002/ppul.23493. Epub 2016 Jun 30. PMID 27362365
  • Nattes E, Lejeune S, Carsin A, Borie R, Gibertini I, Balinotti J, Nathan N, Marchand-Adam S, Thumerelle C, Fauroux B, Bosdure E, Houdouin V, Delestrain C, Louha M, Couderc R, De Becdelievre A, Fanen P, Funalot B, Crestani B, Deschildre A, Dubus JC, Epaud R. Heterogeneity of lung disease associated with NK2 homeobox 1 mutations. Respir Med. 2017 Aug;129:16-23. doi: 10.1016/j.rmed.2017.05.014. Epub PMID 28732825
  • Sun Y, Hu G, Luo J, Fang D, Yu Y, Wang X, Chen J, Qiu W. Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia. J Hum Genet. 2017 Jun;62(6):647-651. doi: 10.1038/jhg.2017.10. Epub 2017 Feb 2. PMID 28148924
  • Braun S, Ferner M, Kronfeld K, Griese M. Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases. Pediatr Pulmonol. 2015 Apr;50(4):410-9. doi: 10.1002/ppul.23133. Epub 2014 Dec 9. PMID 25491573
  • Kroner C, Reu S, Teusch V, Schams A, Grimmelt AC, Barker M, Brand J, Gappa M, Kitz R, Kramer BW, Lange L, Lau S, Pfannenstiel C, Proesmans M, Seidenberg J, Sismanlar T, Aslan AT, Werner C, Zielen S, Zarbock R, Brasch F, Lohse P, Griese M. Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients. Eur Respir J. 2015 Jul;46(1):197-206. doi: 10.1183/09031936.00129 PMID 25657025

Identifiers

NCT: NCT04532346 · QLL202008

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗