Clinical Characteristics of Interstitial Pneumonia With Autoimmune Features (IPAF) - a Multicenter Prospective Study

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

- written informed consent to participate in the study - diagnosis of one of interstitial lung diseases/autoimmune diseases as described below

Exclusion Criteria:

- age < 18 years - withdrawal od consent - pregnancy - lactation - infectious disease 4 weeks prior

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03870828
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Medical University of Silesia
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Szymon Skoczynski, MD, PhD
Principal Investigator Affiliation Slaski Uniwersytet Medyczny
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Not yet recruiting
Countries Italy, Poland
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Interstitial Lung Disease, Interstitial Pneumonia, Interstitial Fibrosis, Autoimmune Diseases
Additional Details

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Poznań, Wielkopolskie, Poland

Status

Not yet recruiting

Address

Katedra i Klinika Pulmonologii, Alergologii i Onkologii Pulmonologicznej Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu

Poznań, Wielkopolskie, 60-514

Site Contact

Halina Batura-Gabryel, Professor

halinagabryel@wp.pl

48618417061

Zabrze, Slask, Poland

Status

Not yet recruiting

Address

Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof. St. Szyszko Sląskiego Uniwersytetu Medycznego w Katowicach

Zabrze, Slask, 41-800

Site Contact

Dariusz Ziora, Professor

zioradar@wp.pl

48323732235

Katowice, Slaskie, Poland

Status

Not yet recruiting

Address

Katedra i Klinika Pneumonologii Slaskiego Uniwersytetu Medycznego w Katowicach

Katowice, Slaskie,

Site Contact

Adam Barczyk, Professor

adagne@icloud.com

48324796101

Gdańsk, Pomorskie, Poland

Status

Not yet recruiting

Address

Klinika Alergologii Gdanskiego Uniwersytetu Medycznego

Gdańsk, Pomorskie, 80-211

Site Contact

Ewa Jassem, Professor

ejassem@gumed.edu.pl

48583492625

Kraków, Malopolskie, Poland

Status

Not yet recruiting

Address

II Katedra Chorob Wewnetrznych Uniwersytetu Jagiellonskiego Collegium Medicum im. prof. A. Szczeklika Szpitala Uniwersyteckiego

Kraków, Malopolskie, 31-066

Site Contact

Krzysztof Sladek, Professor

krzysztof.sladek@uj.edu.pl

48124305147

Lublin, Lubelskie, Poland

Status

Not yet recruiting

Address

Katedra i Klinika Pneumonologii, Onkologii i Alergologii Uniwersytetu Medycznego w Lublinie

Lublin, Lubelskie, 20-400

Site Contact

Janusz Milanowski, Professor

janusz.milanowski@umlub.pl

48817244431

Universita' degli Studi di Messina, Messina, Province Of Messina, Italy

Status

Not yet recruiting

Address

Universita' degli Studi di Messina

Messina, Province Of Messina, 98122

Site Contact

Gaetano Caramori, Professor

pneumologia@polime.it

390906761

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