Pulmonary Disease, Chronic ObstructiveKOLINNCT02729220
Respiratory and Cardiovascular Effects in COPD
A study testing Bronchoscopy in people with Pulmonary Disease, Chronic Obstructive, run by Dr Annelie F Behndig, MD PhD at 1 site in Sweden.
Trial summary
The purpose of this study is to find out if subjects with chronic obstructive pulmonary disease have signs of accelerated ageing in their airways. Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Bronchoscopy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteSweden
- Study dates
- Jan 2012to Dec 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of COPD, GOLD stage 2-3.
- Smoking history of at least 10 packyears.
Who cannot join
- Severe ischemic heart disease.
- Other severe disease.
- Respiratory infection within four weeks.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Department of Public Health and Clinical Medicine, Division of medicine, Pulmonary medicine
Umeå, Sverige, SE-90185
About this study
Official title: Respiratory and Cardiovascular Effects in COPD - Report From a Bronchoscopy Investigation Based on the Obstructive Lung Disease In the Northern Sweden (OLIN) Studies
The purpose of this study is to find out if subjects with chronic obstructive pulmonary disease have signs of accelerated ageing in their airways.
Read the detailed description
The age-related impairment of innate immunity and antioxidant defenses likely impacts on development and disease progression of chronic obstructive pulmonary disease, COPD. It has been suggested that aging-related declines in function are accelerated in COPD due to recurrent cycles of inflammation, tissue injury and repair, associated with long-term exposure to cigarette smoke or other airway irritants. Here, the investigators aim to follow up on previous observations of impaired antioxidant responses in the lung of COPD patients, to establish the extent to which this reflects an accelerated aging phenotype, to characterize the molecular mechanisms resulting in this functional deficiency. The proposed studies will employ well-characterized patients with COPD of varying severity and smoking habits, as well as carefully age and smoking history-matched controls. Accelerated aging within the COPD lung will be assessed in endobronchial mucosal biopsies and airway macrophages by assessment of established senescence markers using immunohistochemical, biochemical and PCR-based methods. These markers of tissue age will then be related to the functional activation of transcription factors, known to be induced by oxidative stress and related to cytoprotection such as Nrf2 and AP1. The investigators will also examine whether COPD is associated with an enhanced secretion of inflammatory mediators from senescent cells, consistent with the accelerated aging paradigm and establish how this influences cell function. Deficiencies in metal handling, antioxidant defenses and diminished airway innate immune defenses at the air-lung interface will be assessed. The aim is to identify biomarkers for the risk of rapid lung function deterioration in COPD patients.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Bronchoscopy
- Keywords
- Aging, Oxidative stress, Proteases, Bronchoscopy
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BronchoscopyOther
Sampling of airways
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Other | Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness Receives: Other: Bronchoscopy |
| Smokers | Other | Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness Receives: Other: Bronchoscopy |
| COPD rapid decline | Other | Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness Receives: Other: Bronchoscopy |
| COPD slow decline | Other | Bronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness Receives: Other: Bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular senescence marker - Ki67
Endobronchial mucosal biopsies collected by bronchoscopy. Immunohistochemistry for the cellular senescence markers Ki67 will be performed.
Measured: Baseline
Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1
Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.
Measured: Baseline
Levels of oxidized proteins, 4 HNE
The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.
Measured: Baseline
Antioxidant-related transcription factor Nrf2
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor known to be induced by oxidative stress and related to cytoprotection.
Measured: Baseline
Secondary outcomes (3)
Metals in airway lavages
Airway lavages collected by bronchoscopy will be analysed for metals using mass spectrometry
Measured: Baseline
Lymphocyte subsets in bronchoalveolar lavage
Airway lavages collected by bronchoscopy will be analysed for lymphocyte subsets using flow cytometry.
Measured: Baseline
Arterial stiffness
Non-invasive measurement of arterial stiffness
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startJan 2012
- Primary completionDec 2014
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 Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr Annelie F Behndig, MD PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr Annelie F Behndig, MD PhD, University Hospital, Umeå
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02729220
- Sponsor's protocol ID
- 2011-147_31M
- Acronym
- KOLIN
- Status last verified
- Mar 2016
- First submitted
- 24 Feb 2016
- Last updated
- 6 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Airway regulatory T cells are decreased in COPD with a rapid decline in lung function. Respir Res. 2020 Dec 14;21(1):330. doi: 10.1186/s12931-020-01593-9.
PubMed 33317530Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking. Respir Res. 2018 Dec 7;19(1):244. doi: 10.1186/s12931-018-0940-7.
PubMed 30526599
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Respiratory and Cardiovascular Effects in COPD - Report From a Bronchoscopy Investigation Based on the Obstructive Lung Disease In the Northern Sweden (OLIN) Studies
- ClinicalTrials.gov ID
- NCT02729220
- Acronym / sponsor ID
- KOLIN / 2011-147_31M
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Aging, Oxidative stress, Proteases, Bronchoscopy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Dr Annelie F Behndig, MD PhDUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Dec 2014 (actual)
- First posted
- 6 Apr 2016 (estimated)
- 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 purpose of this study is to find out if subjects with chronic obstructive pulmonary disease have signs of accelerated ageing in their airways.
Detailed description
The age-related impairment of innate immunity and antioxidant defenses likely impacts on development and disease progression of chronic obstructive pulmonary disease, COPD. It has been suggested that aging-related declines in function are accelerated in COPD due to recurrent cycles of inflammation, tissue injury and repair, associated with long-term exposure to cigarette smoke or other airway irritants. Here, the investigators aim to follow up on previous observations of impaired antioxidant responses in the lung of COPD patients, to establish the extent to which this reflects an accelerated aging phenotype, to characterize the molecular mechanisms resulting in this functional deficiency. The proposed studies will employ well-characterized patients with COPD of varying severity and smoking habits, as well as carefully age and smoking history-matched controls. Accelerated aging within the COPD lung will be assessed in endobronchial mucosal biopsies and airway macrophages by assessment of established senescence markers using immunohistochemical, biochemical and PCR-based methods. These markers of tissue age will then be related to the functional activation of transcription factors, known to be induced by oxidative stress and related to cytoprotection such as Nrf2 and AP1. The investigators will also examine whether COPD is associated with an enhanced secretion of inflammatory mediators from senescent cells, consistent with the accelerated aging paradigm and establish how this influences cell function. Deficiencies in metal handling, antioxidant defenses and diminished airway innate immune defenses at the air-lung interface will be assessed. The aim is to identify biomarkers for the risk of rapid lung function deterioration in COPD patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | Other | Other: BronchoscopyBronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness |
| Smokers | Other | Other: BronchoscopyBronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness |
| COPD rapid decline | Other | Other: BronchoscopyBronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness |
| COPD slow decline | Other | Other: BronchoscopyBronchoscopy with collection of bronchial biopsies and lavages Arterial stiffness |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of COPD, GOLD stage 2-3.
- Smoking history of at least 10 packyears.
Key exclusion criteria (3 listed)
- Severe ischemic heart disease.
- Other severe disease.
- Respiratory infection within four weeks.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BronchoscopySampling of airways | Other | COPD rapid decline, COPD slow decline, Healthy controls, Smokers |
Primary outcome
Cellular senescence marker - Ki67
Time frame: Baseline
Endobronchial mucosal biopsies collected by bronchoscopy. Immunohistochemistry for the cellular senescence markers Ki67 will be performed.
Matrix metalloproteinase 12 (MMP12) and the inhibitor TIMP1
Time frame: Baseline
Airway lavages collected by bronchoscopy and serum will be analysed for MMP and TIMP using ELISAs.
Levels of oxidized proteins, 4 HNE
Time frame: Baseline
The accumulation of oxidized proteins, 4-Hydroxynonenal, will be assessed in bronchial biopsies.
Antioxidant-related transcription factor Nrf2
Time frame: Baseline
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor known to be induced by oxidative stress and related to cytoprotection.
3 secondary outcomes
Metals in airway lavages
Time frame: Baseline
Lymphocyte subsets in bronchoalveolar lavage
Time frame: Baseline
Arterial stiffness
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2016.
- Derived from this study: PubMed 33317530Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Airway regulatory T cells are decreased in COPD with a rapid decline in lung function. Respir Res. 2020 Dec 14;21(1):330. doi: 10.1186/s12931-020-01593-9.
- Derived from this study: PubMed 30526599Eriksson Strom J, Pourazar J, Linder R, Blomberg A, Lindberg A, Bucht A, Behndig AF. Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking. Respir Res. 2018 Dec 7;19(1):244. doi: 10.1186/s12931-018-0940-7.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bronchoscopy in people with Pulmonary Disease, Chronic Obstructive, run by Dr Annelie F Behndig, MD PhD at 1 site in Sweden.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 6 Apr 2016. 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 Sweden. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cellular senescence marker - Ki67 (time frame: Baseline). The study lists 4 primary outcomes in all. 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 NCT02729220, 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 6 Apr 2016.