Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)SHIFTNCT07580053
Hereditary Influences on Pulmonary Fibrosis Trajectories
An observational study of Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder) and Idiopathic Pulmonary Fibrosis (IPF), run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study is a prospective, multicenter, observational cohort study designed to investigate familial pulmonary fibrosis (FPF) within the Italian population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder), Idiopathic Pulmonary Fibrosis (IPF), Telomere Disease
- How many people
- 250 participants
- Where
- 1 siteItaly
- Study dates
- 1 Apr 2026to Dec 2034
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with ILDs discussed in the multidisciplinary discussion to define FPF. Cases discussed will be documented using a standard CRF that detailed complete medical history including genetic test, physical examination, laboratory test results, pulmonary function test (PFT) results and, eventually, lung biopsy results and/or bronchoalveolar lavage (BAL) results. Pre-MDD diagnoses will be based on the referring pulmonologist's diagnosis and current consensus classification for ILDs. Post-MDD diagnosis will be classified according to Ryerson confidence terminology, with "confident diagnosis" reserved for >90% clinical likelihood or a provisional diagnosis which was categorized as "high confidence" (70-89% likelihood) or "low confidence" (51-69% likelihood). Patients with less than 50% diagnostic confidence level post-MDD will be categorized as "unclassifiable ILD".
Who may be able to join
- A HRCT scan consistent with ILD diagnosis
- Age over 18 years old
- A genetic test proved variant or a polymorphism consistent with a diagnosis of FPF
- Ability to give informed consent for the inclusion in the study
Who cannot join
- Patients unable to perform pulmonary function tests
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Observational, Prospective, Multicenter Study on Hereditary Influences on Pulmonary Fibrosis Trajectories
The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study is a prospective, multicenter, observational cohort study designed to investigate familial pulmonary fibrosis (FPF) within the Italian population.
Read the detailed description
Familial pulmonary fibrosis (FPF) is a genetically driven subset of fibrosing interstitial lung diseases (ILDs) characterised by heterogeneous phenotypes, variable clinical trajectories, and limited evidence to guide prognosis and treatment. Although antifibrotic therapies are effective in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), data in FPF, particularly from European populations, remain scarce. The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study aims to prospectively characterize disease progression, treatment response, and outcomes in a national Italian cohort.
SHIFT is a prospective, multicenter, observational cohort study enrolling adults (≥18 years) with ILD on high-resolution computed tomography and genetic findings consistent with FPF. Participants are recruited from specialized ILD referral centers across Italy and followed every 6 months for up to 5 years. Diagnostic attribution is standardized through multidisciplinary discussion using a structured confidence framework. All treatments are prescribed according to routine clinical practice. The primary endpoint is annual relative decline in forced vital capacity (FVC). Secondary endpoints include longitudinal changes in diffusing capacity (DLCO), treatment effectiveness and safety, mortality, transplant-free survival, cancer incidence, and genotype-phenotype and genotype-treatment response associations. Longitudinal data will be analyzed using mixed-effects models, and time-to-event outcomes using survival methods. Multivariable analyses and sensitivity analyses will address confounding.
- Conditions
- Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder), Idiopathic Pulmonary Fibrosis (IPF), Telomere Disease, Progressive Pulmonary Fibrosis, Familial Pulmonary Fibrosis
- Keywords
- PROGRESSIVE PULMONARY FIBROSIS, INTERSTITIAL LUNG DISEASE, TELOMERE DISORDER, FAMILIAL PULMONARY FIBROSIS, IDIOPATHIC PULMONARY FIBROSIS
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Familial pulmonary fibrosis | Eligible participants will be adults (≥18 years) with ILD documented on HRCT and with a positive genetic test, defined as the presence of rare variants or susceptibility polymorphisms consistent with the diagnosis of FPF. |
What is being measured
The primary outcome is the main question the study is designed to answer.
annual relative FVC decline over the observation period
The annual relative decline is defined as the difference between the final and the initial FVC value divided by the initial value, and it will be calculated for each year and for the entire follow-up period.
Measured: Annual for 5 years
Secondary outcomes (4)
relative reduced annual FVC decline when compared to FPF patients treated with immunomodulator agents and FPF patients not treated in a 5-years period of FU.
relative reduced annual FVC decline when compared to FPF patients treated with immunomodulator agents and FPF patients not treated in a 5-years period of FU.
Measured: 5 years
mortality
mortality
Measured: 5 years
Annual relative DLCO decline
Annual relative DLCO decline: The annual relative decline is defined as the difference between the final and the initial DLCO value divided by the initial value, and it will be calculated for each year and for the entire follow-up period.
Measured: 5 years
incidence of lung and non-lung cancer
incidence of lung and non-lung cancer
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2026
- Study start1 Apr 2026
- Primary completionDec 2034 (estimated)
- Study completionDec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)Studies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 250 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Collaborators
- University of Siena, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Ospedale San Paolo
- Responsible party
- Sponsor
- Investigators
- Francesco Amati, MD, Principal investigator, Humanitas Research Hospital IRCCS, Rozzano-Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07580053
- Sponsor's protocol ID
- Prot. Nr.721/25
- Acronym
- SHIFT
- Status last verified
- Apr 2026
- First submitted
- 20 Apr 2026
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zhang D, Newton CA. Familial Pulmonary Fibrosis: Genetic Features and Clinical Implications. Chest. 2021 Nov;160(5):1764-1773. doi: 10.1016/j.chest.2021.06.037. Epub 2021 Jun 26.
PubMed 34186035Borie R, Kannengiesser C, Antoniou K, Bonella F, Crestani B, Fabre A, Froidure A, Galvin L, Griese M, Grutters JC, Molina-Molina M, Poletti V, Prasse A, Renzoni E, van der Smagt J, van Moorsel CHM. European Respiratory Society statement on familial pulmonary fibrosis. Eur Respir J. 2023 Mar 16;61(3):2201383. doi: 10.1183/13993003.01383-2022. Print 2023 Mar.
PubMed 36549714
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational, Prospective, Multicenter Study on Hereditary Influences on Pulmonary Fibrosis Trajectories
- ClinicalTrials.gov ID
- NCT07580053
- Acronym / sponsor ID
- SHIFT / Prot. Nr.721/25
- Conditions
- Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder), Idiopathic Pulmonary Fibrosis (IPF), Telomere Disease, Progressive Pulmonary Fibrosis, Familial Pulmonary Fibrosis
- Keywords
- PROGRESSIVE PULMONARY FIBROSIS, INTERSTITIAL LUNG DISEASE, TELOMERE DISORDER, FAMILIAL PULMONARY FIBROSIS, IDIOPATHIC PULMONARY FIBROSIS
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Collaborators
- University of Siena, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Ospedale San Paolo
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- Dec 2034 (estimated)
- Study completion
- Dec 2034 (estimated)
- First posted
- 12 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study is a prospective, multicenter, observational cohort study designed to investigate familial pulmonary fibrosis (FPF) within the Italian population.
Detailed description
Familial pulmonary fibrosis (FPF) is a genetically driven subset of fibrosing interstitial lung diseases (ILDs) characterised by heterogeneous phenotypes, variable clinical trajectories, and limited evidence to guide prognosis and treatment. Although antifibrotic therapies are effective in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), data in FPF, particularly from European populations, remain scarce. The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study aims to prospectively characterize disease progression, treatment response, and outcomes in a national Italian cohort.
SHIFT is a prospective, multicenter, observational cohort study enrolling adults (≥18 years) with ILD on high-resolution computed tomography and genetic findings consistent with FPF. Participants are recruited from specialized ILD referral centers across Italy and followed every 6 months for up to 5 years. Diagnostic attribution is standardized through multidisciplinary discussion using a structured confidence framework. All treatments are prescribed according to routine clinical practice. The primary endpoint is annual relative decline in forced vital capacity (FVC). Secondary endpoints include longitudinal changes in diffusing capacity (DLCO), treatment effectiveness and safety, mortality, transplant-free survival, cancer incidence, and genotype-phenotype and genotype-treatment response associations. Longitudinal data will be analyzed using mixed-effects models, and time-to-event outcomes using survival methods. Multivariable analyses and sensitivity analyses will address confounding.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Familial pulmonary fibrosis | – | –Eligible participants will be adults (≥18 years) with ILD documented on HRCT and with a positive genetic test, defined as the presence of rare variants or susceptibility polymorphisms consistent with the diagnosis of FPF. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with ILDs discussed in the multidisciplinary discussion to define FPF. Cases discussed will be documented using a standard CRF that detailed complete medical history including genetic test, physical examination, laboratory test results, pulmonary function test (PFT) results and, eventually, lung biopsy results and/or bronchoalveolar lavage (BAL) results. Pre-MDD diagnoses will be based on the referring pulmonologist's diagnosis and current consensus classification for ILDs. Post-MDD diagnosis will be classified according to Ryerson confidence terminology, with "confident diagnosis" reserved for >90% clinical likelihood or a provisional diagnosis which was categorized as "high confidence" (70-89% likelihood) or "low confidence" (51-69% likelihood). Patients with less than 50% diagnostic confidence level post-MDD will be categorized as "unclassifiable ILD".
Key inclusion criteria (4 listed)
- A HRCT scan consistent with ILD diagnosis
- Age over 18 years old
- A genetic test proved variant or a polymorphism consistent with a diagnosis of FPF
- Ability to give informed consent for the inclusion in the study
Key exclusion criteria (1 listed)
- Patients unable to perform pulmonary function tests
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
annual relative FVC decline over the observation period
Time frame: Annual for 5 years
The annual relative decline is defined as the difference between the final and the initial FVC value divided by the initial value, and it will be calculated for each year and for the entire follow-up period.
4 secondary outcomes
relative reduced annual FVC decline when compared to FPF patients treated with immunomodulator agents and FPF patients not treated in a 5-years period of FU.
Time frame: 5 years
mortality
Time frame: 5 years
Annual relative DLCO decline
Time frame: 5 years
incidence of lung and non-lung cancer
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Background: PubMed 34186035Zhang D, Newton CA. Familial Pulmonary Fibrosis: Genetic Features and Clinical Implications. Chest. 2021 Nov;160(5):1764-1773. doi: 10.1016/j.chest.2021.06.037. Epub 2021 Jun 26.
- Background: PubMed 36549714Borie R, Kannengiesser C, Antoniou K, Bonella F, Crestani B, Fabre A, Froidure A, Galvin L, Griese M, Grutters JC, Molina-Molina M, Poletti V, Prasse A, Renzoni E, van der Smagt J, van Moorsel CHM. European Respiratory Society statement on familial pulmonary fibrosis. Eur Respir J. 2023 Mar 16;61(3):2201383. doi: 10.1183/13993003.01383-2022. Print 2023 Mar.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Amati, MD principal investigator
Humanitas Research Hospital IRCCS, Rozzano-Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder) and Idiopathic Pulmonary Fibrosis (IPF), run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
annual relative FVC decline over the observation period (time frame: Annual for 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07580053, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.