Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03870828 |
| Other study ID # |
SilesianMU1 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 18, 2019 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
March 2019 |
| Source |
Medical University of Silesia |
| Contact |
Adam Barczyk, Professor |
| Phone |
+48324796101 |
| Email |
adagne[@]icloud.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Interstitial pneumonia with autoimmune features (IPAF) was defined in 2015 by the Working
Group of the European Respiratory Society (ERS) and the American Thoracic Society (ATS) as
interstitial pneumonia with some clinical and/or serological features suggesting presence of
an underlying autoimmune disorder. However, ofiicial criteria for diagnosis of an autoimmune
disease are not met.
Aims of the study:
1. Determine the incindence of IPAF in comparison with interstitial lung diseases (ILDs)
and classic autoimmune diseases (ADs) in polish pulmonological centers.
2. Clinical, serological, functional and radiological and histopathological characteristics
of IPAF patients.
3. Analysis of diagnostic strategies towards specific IPAF subgroups.
4. Characterictics of potencial diagnostic, predictive and prognostic features of IPAF.
5. Prospective assessment of IPAF patients in the courseof 5 years in order to determine
stability of the diagnosis and potential progression to other diseases, e.g. ADs.
Description:
The following patient groups will be studied:
1. Study group - IPAF.
2. Control groups:
1. Connective tissue disease associated interstitial lung disease (CTD-ILD) patients:
.rheumatoid arthritis - RA, systemic sclerosis - SSc, polymyositis - PM,
dermatomyositis - DM, (anti-synthetase syndrome - AS, Sjoegren's syndrome - SjS,
mixed connective tissue disease - MCTD ,systemic lupus erythematosus - SLE,
diagnosed according to diagnostic criteria issued by European League Against
Rheumatism (EULAR) and/or American College of Rheumatology (ACR)
2. Idiopathic interstitial pneumonia group: idiopathic pulmonary fibrosis - IPF,
nonspecific interstitial pneumonia - NSIP, cryptogenic organizing pneumonia - COP,
acute interstitial pneumonia - AIP; respiratory bronchiolitis associated
interstitial lung disease - RB-ILD, desquamative interstitial pneumonia - DIP,
lymphocytic interstitial pneumonia - LIP).
Methods Patients will be assessed by a pulmonologist and rheumatologist.
Questionnaires regarding clinical symptoms, concomitant diseases and their
treatment, disease activity will be fulfilled.
The majority of diagnostic tests and procedures are routinely performed during
clinical care.
The study will be divided into 2 phases:
1. Phase 1 - visit 1
2. Phase 2 - observation of selected subjects from visit 1 to 5
Phase 1:
30 patients meeting the eligibility criteria, including individuals with a long
medical history and currently undergoing treatment for interstitial lung disease/
autoimmune disorder are going to be recruited to the study in every clinical
center, totaling up to:
- 210 patients in IPAF group
- 210 patients in CTD-ILD group
- 210 patients in IIP group
Phase 2 Only newly diagnosed patients (individuals who have not been previously
diagnosed with interstitial lung disease, and such diagnosis was set during phase 1
of the study) will be recruited to this phase. Due to rare incidence, the
recruitment phase may take up to 36 months.
The total number of patients will be
- 70 in IPAF group
- 70 in CTD-ILD group (RA, SSc, PM, DM)
- 70 in IIP group (35 with IPF and 35 with NSIP, COP and LIP)
Visit 1:
• The following tests and procedures will be performed:
- Detailed anamnesis obtained through 'visit 1 questionnaire' [non-routine
procedure]
- Lung function tests (spirometry with reversibility testing, plethysmography,
diffusion lung capacity for carbon monoxide) [routine procedure]. Absolute
value and % of the reference value will be assessed.
FEV1 - Forced expiratory volume in 1 second FVC - Forced vital capacity VC - Vital
capacity FEV1/VC, ratio TLC - Total lung capacity, DLCO SB - The carbon monoxide
diffusion capacity (single breath method) ITGV - intrathoracic gas volume RV/TLC -
Residual volume/ Total lung capacity ratio
- validated methods of cough assessment [routine procedure]: Chung cough
questionnaire and Visual analogue scale (VAS).
- validated methods of dyspnea assessment [routine procedure]: Likert dyspnea
questionnaire and modified Borg scale.
Blood testing. In total 30 ml blood will be drawn (15 ml blood into a plain
microtube without anticoagulant and 15ml blood into anticoagulation microtube).
Detailed description below:
NT-proBNP, laboratory tests performed during diagnostic process of rheumatologic
diseases and potential IPAF markers [routine procedure]. 15 ml venous blood will be
drawn and divided into 2 microtubes (10 ml and 5 ml) without anticoagulant 10 ml
microtube will be expedited to a local laboratory in order to measure plasma levels
of NT-proBNP and the following autoantibodies' titer:
- rheumatoid factor (RF),
- Anti-Citrullinated Protein Antibodies (ACPA; anti-CCP),
- Antinuclear Antibodies (ANA) (ANA 1 test performed as screening); in case of
ANA presence and further staining pattern identification (e.g. homogenous,
speckled, peripheral, nucleolar, centromere), further tests will be performed
(ANA 2 and ANA 3):
- anti-dsDNA,
- anti-Sm,
- anti-SS-A (Ro),
- anti-SS-B (La),
- anti-Scl-70,
- anti-RNP,
- anti-Jo-1 and anti-PL-7, anti-PL12,
- anti-Mi-2,
- anti-PM-Scl,
- anti-MDA5. From the second 5 ml microtube, after clot has formed, ca
2,5ml serum will be drawn away with a pipette; serum will be later
divided into 5 Eppendorf type microtubes (0,5 ml each). These microtubes
should be labeled according to the following: first letter of the
patient's name- first letter of the patient's surname/ gender F or M/date
of birth DD-MM-YY/date of sample collection DD-MM-YY, e.g.
AL/K/12.05.45/01.02.18. The samples will be stored in -70 °C. The samples
will be collected by a courier and transported to the clinical center
responsible for this part of the study. This sample will be used to test
for potential IPAF markers, e.g. chemokine C-C motif ligand 18 (CXCL18),
Surfactant Protein A- (SP-A), Surfactant Protein D (SP-D), Krebs von den
Lungen-6 protein (KL-6) and chitotrisidase 1 (CHIT1) [non-routine
procedure].
Blood sample collection [procedure not routinely performed during clinical care].
15 ml of whole venous blood will be drawn and then divided into 10 Eppendorf tubes
1, 5 ml each. The tubes will be labeled as described above. The specimens will be
stored in -70 °C. The samples will be transported to the clinical center
responsible for this part of the study.
Optionally, additional tests (testing for proteomic and metabolomic biomarkers)
will be performed in samples of biological material collected beforehand (BALF,
serum, urine [non-routine procedure].
o Bronchofiberoscopy with bronchalveolar lavage (BF + BAL), performing biopsy of
the bronchi mucosa: BF + BAL [routine procedure]: before starting BF, regional
anesthesia and sedation with use of lidocaine and midazolam will be performed,
according to anesthesia protocols applied in respective endoscopy units.
Intravenous cannula will be inserted prior to BF. During endoscopy, the patient
will be monitored according to safety protocols applied in respective endoscopy
units.
Bronchoalveolar lavage will be performed in the bronchus from the middle robe of
right lung or the lingula of left lung (B4, B5). Localization will be chosen based
on HRCT results and will be recorded in patient's medical history. Sterile solution
of 0, 9% NaCl will be instilled. 200 ml fluid will be applied with a syringe in
portions of 25 ml or 50 ml. It is recommended that minimum 60 % of the lavage fluid
is retrieved.
Bronchoalveolar lavage fluid (BALF) testing. Preparation of microscopic slides,
analysis of the cellular components of the specimen (kind of the most abundant
cells retrieved, the cells' durability) will be performed according to a standard
laboratory procedure (guidelines of the Polish Respiratory Society). Total cell
count along with cells' durability will be measured in a sample taken from the
filtrate or material after the first spin. Cytospin (routinely 10 min of 1200-2000
rpm) will be used to prepare the material. May-Grunewald-Giemsa stain will be used
to prepare the microscopic slides.
BALF samples will be secured and stored in order to test for potential IPAF
markers. 15 ml BALF will be divided into Eppendorf 1,5 ml microtubes and then
stored in - 70 C. Samples will be checked for concentration of S1009A protein,
chemokine (C-C motif) ligand 2 and chitotrisidase 1 (CHIT 1).
Specimens of bronchial mucosa taken during BF [procedure not routinely performed
during clinical care]. 5 mucosa specimens will be taken from the initial segment of
the middle lobe bronchus, placed into Eppendorf microtubes and stored in -80 C.
Specimen will be sent for histopathological assessment.
- 6 minute walking test - (6MWT) performed according to a protocol applied in
respective clinical centers [routine procedure]. The following data should be
recorded:
• Whether the patient completed the test. If 6MWT was interrupted, the reason
should be recorded (e.g. dyspnea, high blood pressure, cardiac arrhythmia,
intermittent claudication, other)
- Distance in meters
- Pulse oximetry measured before and directly after the test
- Dyspnea measurement - Borg scale
- High resolution computed tomography (HRCT) [routine procedure]. Current
tomography, performed according to protocol applied in respective clinical
centers or CT 6 months prior to the study will be eligible. Test results
(saved on CD) and radiological description will be used. CD will be labeled in
a way described above. OsiriX Lite software will be used to assess the scans.
The following densitometric values will be measured: mean lung attenuation
(MLA), kurtosis, skewness, and standard deviation of lung radiodensity (SD
I.R). Data analysis will be performed with Statistica software. Data will be
presented as median and interquartile ranges (IQR). Quantitative data will be
analyzed with Kruskal-Willis' and Dunn's post hoc tests
- Pulse oximetry (SpO2) [routine procedure]. If SpO2 is measured to be < 92% or
if there are indications for oxygen therapy, arterial blood gas will be
performed.
- Transthoracic echocardiography (TTE) [routine procedure] with detailed right
heart assessment:
Pulmonary artery diameter Acceleration time (Act) and pulmonary regurgitation
Tricuspid annulus systolic velocity Tricuspid regurgitation velocity. Tricuspid
annular plate systolic excursion, (TAPSE) Basal right ventricle (RV) diameter, mid
RV diameter and base-apex dimension Right ventricle inflow tract dimension Right
ventricle outflow tract dimension Right ventricle diameter measured at the level of
pulmonary valve Right atrial volume Superior vena cava dimension Inferior vena cava
dimension Right ventricular wall thickness (RVWT)
o Rheumatology consultation of every patient in IPAF and autoimmune disorder groups
[procedure routinely performed during clinical care].
Qualification for visit 2-5 - only patients qualified to phase 2 of the study
Visit 2:
• 6 +/- 3 months from visit 1:
o Visit 1-5 questionnaire [non-routine procedure]
- Lung function tests [routine procedure]
- 6MWT [routine procedure]
- Pulse oximetry [routine procedure]
Visit 3:
• 12 +/- 3 months from visit 1:
- Visit 1-5 questionnaire [non-routine procedure]
- Lung function tests [routine procedure]
- 6MWT [routine procedure]
- HRCT [routine procedure]
- Blood testing (basic laboratory tests [routine procedure], screening for
autoantibodies and cytokine concentration [non-routine procedure]
- BF + BAL [optionally; routine procedure]
- Arterialized capillary blood gas [routine procedure]
- TTE with detailed right heart assessment [routine procedure]
- Rheumatology consultation [routine procedure]
Visit 4:
- 24 +/- 3 months from visit 1:
- Visit 1-5 questionnaire [non-routine procedure]
- Lung function tests [routine procedure]
- 6MWT [routine procedure]
- HRCT [routine procedure]
- Blood testing (basic laboratory tests [routine procedure], screening for
autoantibodies and cytokine concentration [non-routine procedure]
- BF + BAL (optionally; routine procedure]
- Arterialized capillary blood gas [routine procedure]
Visit 5 • 60 +/- 3 months from visit 1 o Visit 1-5 questionnaire [non-routine
procedure]
- Lung function tests [routine procedure]
- 6MWT [routine procedure]
- HRCT [routine procedure]
- Blood testing (basic laboratory tests [routine procedure], screening for
autoantibodies and cytokine concentration [non-routine procedure]
- BF + BAL (optionally; routine procedure)
- Arterialized capillary blood gas testing [routine procedure]
- TTE with detailed right heart assessment [routine procedure]
- Rheumatology consultation [routine procedure]
- Optionally, in case of clinical and/or radiological progression, worsening of
lung function tests' results, criobiopsy. may be repeated after obtaining
informed patient consent.
