Hydroxychloroquine in Children's Interstitial Lung Diseases With Genetic Causes

Study Overview
=================
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.

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

Conditions
-----------------
Interstitial Lung Disease, Surfactant Dysfunction

Intervention / Treatment
-----------------
* Drug: Hydroxychloroquine


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Hydroxychloroquine in a dose of 10 mg/kg*d, p.o., bid for 12 months. The maximum daily dose is 400mg. | Drug: Hydroxychloroquine<br>* 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.<br>|
| No Intervention: control<br>control group which do not take hydroxychloroquine for treatment. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |