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Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes

Primary Purpose

Interstitial Lung Disease, Surfactant Dysfunction

Status

Not yet recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Hydroxychloroquine

About this trial

This is an interventional treatment trial for Interstitial Lung Disease

Eligibility Criteria

1 Month - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Children's hospital of Fudan University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Hydroxychloroquine

control

Arm Description

Hydroxychloroquine in a dose of 10 mg/kg*d, p.o., bid for 12 months. The maximum daily dose is 400mg.

control group which do not take hydroxychloroquine for treatment.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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".

Full Information

NCT ID

NCT04532346

First Posted

August 26, 2020

Last Updated

August 30, 2023

Sponsor

Children's Hospital of Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT04532346

Brief Title

Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

September 2023 (Anticipated)

Primary Completion Date

October 2025 (Anticipated)

Study Completion Date

April 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Children's Hospital of Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Interstitial Lung Disease, Surfactant Dysfunction

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hydroxychloroquine

Arm Type

Experimental

Arm Description

Hydroxychloroquine in a dose of 10 mg/kg*d, p.o., bid for 12 months. The maximum daily dose is 400mg.

Arm Title

control

Arm Type

No Intervention

Arm Description

control group which do not take hydroxychloroquine for treatment.

Intervention Type

Drug

Intervention Name(s)

Hydroxychloroquine

Intervention Description

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 Measure Information:

Title

Oxygenation status

Description

Time Frame

at first month, at 3rd month, at 6th month, at 12th month

Secondary Outcome Measure Information:

Title

Improvement in clinical manifestation

Description

Time Frame

at first month, at 3rd month, at 6th month, at 12th month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Month

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Liling Qian, Doctor

Phone

021-64931913

llqian@126.com

Facility Information:

Facility Name

Children's hospital of Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

201102

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

23905526

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. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy. Am J Respir Crit Care Med. 2013 Aug 1;188(3):376-94. doi: 10.1164/rccm.201305-0923ST.

Results Reference

result

PubMed Identifier

26135832

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 children. Thorax. 2015 Nov;70(11):1078-84. doi: 10.1136/thoraxjnl-2015-207349. Epub 2015 Jul 1.

Results Reference

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PubMed Identifier

17885266

Citation

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Results Reference

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PubMed Identifier

27362365

Citation

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Results Reference

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PubMed Identifier

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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 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 2017 May 26.

Results Reference

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PubMed Identifier

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Citation

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Results Reference

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Citation

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Results Reference

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Citation

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Results Reference

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Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes

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