Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes

Interstitial Lung Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04532346
• Other study ID #: QLL202008
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: March 2024
• Est. completion date: October 2026

Study information

• Verified date: November 2023
• Source: Children's Hospital of Fudan University
• Contact: Liling Qian, Doctor
• Phone: 021-64931913
• Email: llqian[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: October 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Interstitial Lung Disease
• Lung Diseases
• Lung Diseases, Interstitial
• Surfactant Dysfunction

Intervention

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.

Locations

Country	Name	City	State
China	Children's hospital of Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Fudan University

Country where clinical trial is conducted

China, 

References & Publications (8)

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. — View Citation

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 — View Citation

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, Tr — View Citation

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 d — View Citation

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. A — View Citation

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. — View Citation

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 — View Citation

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.2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxygenation status	It is a repeated measurement variable. It is a binary variable (1/0). In a patient without supplemental O2, increase=5% in O2 saturation or decrease in respiratory rate=20% means significant change or responder to hydroxychloroquine and the varibale would be setted into "1". In a patient with supplemental O2, increase=5% in O2 saturation or decrease in respiratory rate=20% or withdrawal of O2 means significant change or responder to hydroxychloroquine and the varibale would be setted into "1". If no supplemental O2 is necessary, the O2 saturation and respiratory rate are measured in an awake patient after 5 min at rest. If the patient needs supplement O2 , the supplementation is withdrawn after 5 min at rest and the O2 saturation and respiratory rate are measured.	at first month, at 3rd month, at 6th month, at 12th month
Secondary	Improvement in clinical manifestation	It is a repeated measurement variable. It is a binary variable (1/0). If coughing resolved, intercostal retraction disappeared and weight for height back to normal is observed in a patient or improvement in chest radiography and pulmonary function tests is present, it means improvement in clinical manifestation and the variable would be setted into "1".	at first month, at 3rd month, at 6th month, at 12th month