COPDRe-MAPNCT06935825
Respiratory Muscles in End-stage Lung Disease: Pathophysiological Processes & Clinical Consequences
An observational study of COPD, run by University Medical Center Groningen at 4 sites in Netherlands.
Trial summary
Rationale: In patients with chronic lung diseases, the role of respiratory muscle dysfunction has been underestimated. Also, current treatment options, like chronic NIV and lung transplantation (LTx), might also have deleterious effects on the respiratory muscles, and the mechanisms are poorly understood. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- COPD
- How many people
- 60 participants
- Where
- 4 sitesNetherlands
- Study dates
- 1 Sep 2025to 1 Sep 2029
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: COPD patients on the lung transplantation waiting list
In order to be eligible to participate in this study, a participant must meet all of the following criteria:
- Age > 18 years old
- Severe COPD defined as COPD GOLD stage III or IV (FEV1 < 50% of predicted; FEV1/FVC ratio < 70%, no significant reversibility, smoking history of at least 10 pack-years).
- Being on the lung transplant waiting list
- Being able to understand the patient information and provide written informed consent for participation in the study
A potential participant who meets any of the following criteria will be excluded from participation in this study:
- Patients suffering from acute conditions at the time of inclusion or LTx
- Patients using more than 20 mg of morphine, or an equivalent, or more than 20 mg oxazepam, or an equivalent, at the time of inclusion or LTx
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands4 sites, 4 recruiting
- Not yet recruiting
Amsterdam University Medical Center
Amsterdam
Coen Ottenheijm, Prof. Dr., c.ottenheijm@amsterdamumc.nl
- Recruiting
University Medical Center Groningen
Groningen
Marieke Duiverman, m.l.duiverman@umcg.nl
Tji Gan, MD PhD, c.t.gan@umcg.nl
- Not yet recruiting
Radboud University Medical Center
Nijmegen
Jonne Doorduin, jonne.doorduin@radboudumc.nl
- Recruiting
Erasmus Medical Center
Rotterdam
Merel Hellemons, MD PhD, m.hellemons@erasmusmc.nl
About this study
Official title: Respiratory Muscles in End-stage Lung Disease: PAthophysiological Processes & Clinical Consequences
Rationale: In patients with chronic lung diseases, the role of respiratory muscle dysfunction has been underestimated. Also, current treatment options, like chronic NIV and lung transplantation (LTx), might also have deleterious effects on the respiratory muscles, and the mechanisms are poorly understood.
Therefore in this exploratory study the objectives are to:
Read more
- Determine in vivo respiratory muscle function and progression of respiratory muscle dys-function in end-stage COPD patients
- Establish the correlation between changes in the structure and contractility of respiratory myofibers and in vivo respiratory muscle function.
- Establish the effect of chronic NIV on structure and contractility of respiratory muscle fi-bers
- Determine whether the structure and contractility of respiratory muscles cells at the time of LTx predicts clinical recovery post-LTx.
Study design: The study will be an exploratory observational cohort study following patients on the LTx waiting list during the waiting period and afterwards until they showed functional recovery of respiratory muscle function.
Study population: Adult COPD patients on the LTx waiting list will be included. Intervention (if applicable): None
Main study parameters/endpoints:
To assess clinical functioning of the respiratory muscles we will assess respiratory electrical activity as a measure of respiratory effort by surface EMG, and thickening fraction of the diaphragm and intercostal muscles and diaphragm excursions by ultrasound and maximal in- and expiratory pressure to assess muscle output; all before and after LTx. We will relate and correct these data for hyperinflation and degree of lung damage by using data from standard care lung function tests and CT scans, and will relate these measurements to prior treatment (NIV settings) and outcome after LTx, by retrieving these data from the EPD.
To assess contractility of respiratory myofibers and in vivo respiratory muscle function, biopsies will be taken during LTx surgery and the biopsies will be analyzed in the lab of Prof. Ottenheijm (AmsterdamUMC) for individual myofiber functioning (strength, calcium sensitivity, myofiber characteristics) and in the lab of Dr. Pouwels for extracellular matrix characteristics.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Overall, risks are believed to be minimal. The clinical measurements are non-invasive and/or regular performed in clinical practice. Also, we decided to do those measurements during regular control visits, limiting the burden for the patients. Taking biopsies from the respiratory muscles during surgery has been extensively performed without any risk; the biobank of the Ottenheijm group contains > 500 samples and never any complication has been observed. Also, in preparation of the present study we performed a pilot study in 12 COPD patients of whom.. biopsies were taken at the UMCG without side effects or complications. The biopsies will be done with the patients being under full anesthesia, so participants will feel no discomfort.
Read the detailed description
Considering that a) there is a substantial proportion of patients with severe COPD that develop respiratory muscle dysfunction-induced CHRF; b) respiratory pump failure results in significant morbidity and mortality; and c) the response to current treatment options is highly variable, presumably due to detrimental effects on the respiratory muscle pump, there is a high need for research identifying the pathophysiological mechanisms that underlie respiratory muscle dysfunction in end stage COPD. To meet this need, we will combine in vivo respiratory muscle testing with studies on unique respiratory muscle biopsies to test the hypothesis that respiratory muscle dysfunction is caused by atrophy and reduced contractility of single respiratory myofibers, and that this underlies the development of CHRF. Furthermore, we will test the hypothesis that respiratory muscle dysfunction is exacerbated by NIV and contributes to difficulties in post-LTx recovery. The outcomes will identify targets for intervention and prevention of CHRF.
- Conditions
- COPD
- Keywords
- COPD, NIV, Lung transplantation, Respiratory muscles, diaphragm, ultrasound, sEMG, MIP
- 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.
| Study group | Role | What they receive |
|---|---|---|
| NIV+ | Group of patients on nocturnal NIV prior to LTx | |
| NIV-/hypercapnic | Group of patients who are chronic hypercapnic but not on NIV prior to LTx | |
| normocapnic | Group of normocapnic patients prior to LTx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory neural drive
With surface EMg (sEMG) a measure of respiratory neural drive is obtained, which could be used as stand alone parameter to estimate effort and, when combined with output parameters as diaphragm movement or MIP/MEP, might be useful to estimate neuro-ventilatory efficiency.
Measured: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx
Respriatory muscle output - contraction and movement
With ultrasound, we will measure diaphragm and intercostal thickening fraction (DF-TF) thereby investigating the amount of muscle contraction. Diaphragm excursion will be measured from subcostally.
Measured: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx
Respriatory muscle output - strength
Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) will be measured at the lung function department according to ERS guidelines or by using a handheld device when patients are at the ward. Patients are asked to inhale and exhale deeply against a resistance and then measuring airway pressure produced.
Measured: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx
Myofiber mechanics
The maximum force generating capacity, the force response to a range of submaximal [Ca2+], active stiffness (reflecting the number of attached and non-attached myosin heads) is determined of individual myofibers.
Measured: Biopsies are obtained during LTx
Low angle X-ray diffraction
Measure the position of myosin heads in relaxed and in activated myofibers
Measured: Biopsies are obtained during LTx
Mant-ATP chase experiments
To biochemically assess the percentage of myosin heads in the SRX state
Measured: Biopsies are obtained during LTx
Myofiber and extra-cellular matrix structure
We will assess myofiber size by immunohistochemistry using antibodies that label the sarcolemma and myosin heavy chain isoforms
Measured: Biopsies are obtained during LTx
Transcriptomic and proteomic analyses of muscle biopsies
To study the activation of fibrosis pathways we will apply RNAseq and proteomics on the biopsies
Measured: Biopsies are obtained during LTx
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2025
- Study start1 Sep 2025
- Primary completion1 Apr 2029 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COPDStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Amsterdam UMC, location VUmc, Radboud University Medical Center, ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06935825
- Sponsor's protocol ID
- PaNaMaID: 22059
- Acronym
- Re-MAP
- Status last verified
- Jun 2026
- First submitted
- 3 Apr 2025
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: With such a specific group it is too difficult to keep it anonomyzed
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Respiratory Muscles in End-stage Lung Disease: PAthophysiological Processes & Clinical Consequences
- ClinicalTrials.gov ID
- NCT06935825
- Acronym / sponsor ID
- Re-MAP / PaNaMaID: 22059
- Conditions
- COPD
- Keywords
- COPD, NIV, Lung transplantation, Respiratory muscles, diaphragm, ultrasound, sEMG, MIP
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Amsterdam UMC, location VUmc, Radboud University Medical Center, ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 1 Sep 2025 (actual)
- Primary completion
- 1 Apr 2029 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 20 Apr 2025 (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.
Rationale: In patients with chronic lung diseases, the role of respiratory muscle dysfunction has been underestimated. Also, current treatment options, like chronic NIV and lung transplantation (LTx), might also have deleterious effects on the respiratory muscles, and the mechanisms are poorly understood.
Therefore in this exploratory study the objectives are to:
- Determine in vivo respiratory muscle function and progression of respiratory muscle dys-function in end-stage COPD patients
- Establish the correlation between changes in the structure and contractility of respiratory myofibers and in vivo respiratory muscle function.
- Establish the effect of chronic NIV on structure and contractility of respiratory muscle fi-bers
- Determine whether the structure and contractility of respiratory muscles cells at the time of LTx predicts clinical recovery post-LTx.
Study design: The study will be an exploratory observational cohort study following patients on the LTx waiting list during the waiting period and afterwards until they showed functional recovery of respiratory muscle function.
Study population: Adult COPD patients on the LTx waiting list will be included. Intervention (if applicable): None
Main study parameters/endpoints:
To assess clinical functioning of the respiratory muscles we will assess respiratory electrical activity as a measure of respiratory effort by surface EMG, and thickening fraction of the diaphragm and intercostal muscles and diaphragm excursions by ultrasound and maximal in- and expiratory pressure to assess muscle output; all before and after LTx. We will relate and correct these data for hyperinflation and degree of lung damage by using data from standard care lung function tests and CT scans, and will relate these measurements to prior treatment (NIV settings) and outcome after LTx, by retrieving these data from the EPD.
To assess contractility of respiratory myofibers and in vivo respiratory muscle function, biopsies will be taken during LTx surgery and the biopsies will be analyzed in the lab of Prof. Ottenheijm (AmsterdamUMC) for individual myofiber functioning (strength, calcium sensitivity, myofiber characteristics) and in the lab of Dr. Pouwels for extracellular matrix characteristics.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Overall, risks are believed to be minimal. The clinical measurements are non-invasive and/or regular performed in clinical practice. Also, we decided to do those measurements during regular control visits, limiting the burden for the patients. Taking biopsies from the respiratory muscles during surgery has been extensively performed without any risk; the biobank of the Ottenheijm group contains > 500 samples and never any complication has been observed. Also, in preparation of the present study we performed a pilot study in 12 COPD patients of whom.. biopsies were taken at the UMCG without side effects or complications. The biopsies will be done with the patients being under full anesthesia, so participants will feel no discomfort.
Detailed description
Considering that a) there is a substantial proportion of patients with severe COPD that develop respiratory muscle dysfunction-induced CHRF; b) respiratory pump failure results in significant morbidity and mortality; and c) the response to current treatment options is highly variable, presumably due to detrimental effects on the respiratory muscle pump, there is a high need for research identifying the pathophysiological mechanisms that underlie respiratory muscle dysfunction in end stage COPD. To meet this need, we will combine in vivo respiratory muscle testing with studies on unique respiratory muscle biopsies to test the hypothesis that respiratory muscle dysfunction is caused by atrophy and reduced contractility of single respiratory myofibers, and that this underlies the development of CHRF. Furthermore, we will test the hypothesis that respiratory muscle dysfunction is exacerbated by NIV and contributes to difficulties in post-LTx recovery. The outcomes will identify targets for intervention and prevention of CHRF.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NIV+ | – | –Group of patients on nocturnal NIV prior to LTx |
| NIV-/hypercapnic | – | –Group of patients who are chronic hypercapnic but not on NIV prior to LTx |
| normocapnic | – | –Group of normocapnic patients prior to LTx |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- COPD patients on the lung transplantation waiting list
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
Respiratory neural drive
Time frame: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx
With surface EMg (sEMG) a measure of respiratory neural drive is obtained, which could be used as stand alone parameter to estimate effort and, when combined with output parameters as diaphragm movement or MIP/MEP, might be useful to estimate neuro-ventilatory efficiency.
Respriatory muscle output - contraction and movement
Time frame: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx
With ultrasound, we will measure diaphragm and intercostal thickening fraction (DF-TF) thereby investigating the amount of muscle contraction. Diaphragm excursion will be measured from subcostally.
Respriatory muscle output - strength
Time frame: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx
Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) will be measured at the lung function department according to ERS guidelines or by using a handheld device when patients are at the ward. Patients are asked to inhale and exhale deeply against a resistance and then measuring airway pressure produced.
Myofiber mechanics
Time frame: Biopsies are obtained during LTx
The maximum force generating capacity, the force response to a range of submaximal [Ca2+], active stiffness (reflecting the number of attached and non-attached myosin heads) is determined of individual myofibers.
Low angle X-ray diffraction
Time frame: Biopsies are obtained during LTx
Measure the position of myosin heads in relaxed and in activated myofibers
Mant-ATP chase experiments
Time frame: Biopsies are obtained during LTx
To biochemically assess the percentage of myosin heads in the SRX state
Myofiber and extra-cellular matrix structure
Time frame: Biopsies are obtained during LTx
We will assess myofiber size by immunohistochemistry using antibodies that label the sarcolemma and myosin heavy chain isoforms
Transcriptomic and proteomic analyses of muscle biopsies
Time frame: Biopsies are obtained during LTx
To study the activation of fibrosis pathways we will apply RNAseq and proteomics on the biopsies
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 22 Jul 2026.
- Individual participant dataSharing planned: No. With such a specific group it is too difficult to keep it anonomyzed
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COPD, run by University Medical Center Groningen at 4 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands. 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?
Contact Marieke L Duiverman, MD PhD (+31503616161, m.l.duiverman@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory neural drive (time frame: 3-6 monthly before LTx, directly before and after LTx, 3-6 monthly after LTx). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jul 2026.