Pulmonary EmphysemaPhase 2NCT04918706
Allogeneic MSC Treatment for Pulmonary Emphysema
A Phase 2 study testing Allogeneic MSC in people with Pulmonary Emphysema and Mesenchymal Stromal Cells, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Read more about this study
- Who is it for?
- Ages 45 to 65 years
- Conditions the study is for
- Pulmonary Emphysema, Mesenchymal Stromal Cells
- What is being tested?
- Allogeneic MSC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 25 Jun 2019to 1 Jun 2022
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial;
- Scheduled for lung volume reduction surgery for emphysema as determined by a referring chest physician;
- Pre-bronchodilator measured FEV1 between 20% and 45% predicted; TLCO between 30% and 45% pred.; RV/TLC ≥ 50%;
- Patients in a stable clinical condition.
Who cannot join
- Significant cardiac failure;
- Active smoking, or < 6 months smoking cessation;
- Failure to complete pulmonary rehab program before randomization
- Women of child bearing potential;
- Any cancer treated in the previous 5 years;
- Women of child-bearing potential not using adequate contraception;
- Any other condition of the patient that the clinical investigator deemed harmful for study participation.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Department of Pulmonology, Leiden University Medical Center
Leiden, 2333 ZA
Jan Stolk, MD, +31715262950 ext. +31715262950, jstolk@lumc.nl
Jan Stolk, MD
About this study
Official title: An Explorative Study for Halting Inflammation in Patients With Emphysema by Administration of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells.
Rationale: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Bone marrow-derived mesenchymal stromal cells have potential to halt the progressive inflammatory response as indicated by the investigator's pilot study (CCMO NL28562.000.09) .
Objective: To determine whether patients with emphysema develop anti-inflammatory and tissue repair responses by treatment with allogeneic bone marrow-derived mesenchymal stromal cells (MSC) from healthy donors.
Read more
Study design: an explorative double-blind, placebo-controlled randomized (2:1) trial in 30 patients with moderate to severe emphysema who are scheduled for two separate sessions for surgical lung volume reduction (LVRS). The study treatment is intravenous allogeneic MSC or placebo treatment in between the first and second surgical session. Randomisation will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to receive placebo) at week 4 and 3 before the second LVRS, and will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to placebo) at week 12 and 11 before the second LVRS.
Main study parameters/endpoints: the study has a co-primary endpoint. First, the difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo. Second, the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2.
Read the detailed description
Rationale: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Since 25 years, patients with moderate to severe emphysema are treated with inhaled or oral corticosteroids. Currently, consensus is developing that this anti-inflammatory treatment is not effective to halt progression of emphysema. Therefore, emphysema may be classified as steroid-resistant and requires new anti-inflammatory treatment approaches, including cellbased therapies. Bone marrow-derived mesenchymal stromal cells have potential to halt the progressive inflammatory response in various diseases, including steroid-resistant transplant rejection, Crohn's disease and possibly emphysema as indicated by our pilot study (CCMO NL28562.000.09) .
Objective: To determine whether patients with emphysema develop anti-inflammatory and tissue repair responses by treatment with allogeneic bone marrow-derived mesenchymal stromal cells (MSC) from healthy donors.
Study design: an explorative double-blind, placebo-controlled randomized (2:1) trial in 30 patients with moderate to severe emphysema who are scheduled for two separate sessions for surgical lung volume reduction (LVRS). The study treatment is intravenous allogeneic MSC or placebo treatment in between the first and second surgical session. Randomisation will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to receive placebo) at week 4 and 3 before the second LVRS, and will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to placebo) at week 12 and 11 before the second LVRS.
Study population: patients between age 45 and 65; a gradient of emphysema severity towards the lung apex as assessed by CT-derived lung densitometry and equally distributed between left and right lung; FEV1 between 20% and 45% pred; Gas diffusion capacity between 30% and 45% pred. Intervention (if applicable): MSC infusions with cryo-preserved MSC in a dose of 2 x 106 /kg body weight in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg ( at a maximum of 200 x106 MSC per study participant) in a covered bag or NaCl 0.9% with 5% DMSO in a covered bag, both produced in the GMP facility of LUMC.
Main study parameters/endpoints: the study has a co-primary endpoint. First, the difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo. Second, the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: LVRS is a routine procedure for treatment of emphysema and received a positive recommendation from the Cochrane Institute. The dose of MSC has been infused in over 200 patients in LUMC only causing mild side effects like fever and headache, mostly related to DMSO, which is present as a cryoprotectant in the verum. Placebo may also cause fever and headache (DMSO). For the study, additional physical exams will be performed 6 monthly for a period of 3 years after LVRS2 and additional blood sampling specific for the study protocol will be 50ml in total. A heparinized blood sample of 10 ml per sample will be taken: 1) just before the 1st LVRS while patient is under general anaesthesia, 2) just before the 1st MSC iv, 3) just before the 2nd MSC iv, 4) just before the 2nd LVRS while the patient is under general anaesthesia. Discomfort for the patient caused by the experimental treatment will be minimal while there is no reason to assume that hospital admission for the surgery will be prolonged by the cell therapy or placebo. The risks associated with the investigational treatment are low as the reported adverse events in Toetsing Online from previous MSC studies in LUMC show only mild to moderate severity. The risk-benefit analysis is low.
- Conditions
- Pulmonary Emphysema, Mesenchymal Stromal Cells
- Being tested
- Allogeneic MSC, Placebo
- Keywords
- Allogeneic mesenchymal stromal cells, Pulmonary Emphysema, Long volume reduction surgery, Inflammation
- Medical subject headings
- Pulmonary Emphysema, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic MSCGenetic
These MSCs will originate from bone marrow that will be aspirated from healthy volunteer donors screened by a trained physician of the center for stem cell therapy of LUMC
PlaceboDrug
The placebo will be an equivalent volume NaCl 0,9% and DMSO 5%
| Study group | Role | What they receive |
|---|---|---|
| MSC week 4 and 3 before LVRS2 | Experimental | Allogeneic mesenchymal Stromal cells: 2 x 10^6/kg body weight MSC in a range of 1.5 x 10^6 MSC/ kg to 2.5 x 10^6 MSC/kg (at a maximum of 200 x10^6 MSC per study participant) with 5% DMSO iv Receives: Genetic: Allogeneic MSC |
| Placebo week 4 and 3 before LVRS2 | Placebo comparator | Placebo: consisting of a 5% DMSO-solution in isotonic solution Receives: Drug: Placebo |
| MSC week 12 and 11 before LVRS2 | Experimental | Allogeneic mesenchymal Stromal cells: 2 x 10^6/kg body weight MSC in a range of 1.5 x 10^6 MSC/ kg to 2.5 x 10^6 MSC/kg (at a maximum of 200 x10^6 MSC per study participant) with 5% DMSO iv Receives: Genetic: Allogeneic MSC |
| Placebo week 12 and 11 before LVRS2 | Placebo comparator | Placebo: consisting of a 5% DMSO-solution in isotonic solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in expression of CD31
The difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo
Measured: Within one year after the last study patient had its second lung surgical procedure
The difference between MSC and placebo treatment in change in CO diffusion capacity
The difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2
Measured: 1 year after the last CO diffusion measurement
Secondary outcomes (5)
The differences in expression of Surfactant Protein-C expression by alveolar type II cells in lung tissue obtained from study patients treated with placebo or MSC.
Measured: Within one year after the last study patient had its second lung surgical procedure
The difference in immunostaining of various leukocytes in resected lung tissue, including T lymphocytes, B lymphocytes, macrophages and neutrophils obtained from study patients treated with placebo or MSC.
Measured: Within one year after the last study patient had its second lung surgical procedure
The difference in shear stress responses, expressed as % elongation of 100 cells, of isolated pMVECs ex vivo obtained from study patients treated with placebo or MSC.
Measured: Within one year after the last study patient had its second lung surgical procedure
The difference in endothelial microparticles concentration and concentration of immunological markers in blood samples from study patients treated with placebo or MSC.
Measured: Within one year after the last study patient had its second lung surgical procedure
The correlation between arterial pO2 or gas transfer value TLCO (measured as standard of care) and the outcome of the primary objective of the study for patients treated with MSC or placebo.
Measured: at 12 weeks, as well as after 6 and 12 months, after discharge of admission for LVRS2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2021
- Study start25 Jun 2019
- Primary completion1 Sep 2021 (estimated)
- Study completion1 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (39)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmphysemaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomisation (2:1) will allocate 30 patients to two treatment groups. The first group will receive either 2 x 10\^6/kg body weight MSC in a range of 1.5 x 10\^6 MSC/ kg to 2.5 x 10\^6 MSC/kg (at a maximum of 200 x10\^6 MSC per study participant) with 5% DMSO iv or placebo (consisting of a 5% DMSO-solution in isotonic solution) at week 4 and 3 before the second LVRS. The second group will receive either the same dose of 2 x 10\^6/kg body weight MSC iv or placebo at week 12 and 11 before the second LVRS.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Amsterdam UMC, location VUmc
- Responsible party
- Principal investigator, Jan Stolk, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04918706
- Sponsor's protocol ID
- HEP study
- Status last verified
- Jun 2021
- First submitted
- 3 Nov 2020
- Last updated
- 9 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mitzner W. Emphysema--a disease of small airways or lung parenchyma? N Engl J Med. 2011 Oct 27;365(17):1637-9. doi: 10.1056/NEJMe1110635. No abstract available.
PubMed 22029986Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011 Sep 10;378(9795):1015-26. doi: 10.1016/S0140-6736(11)60988-4.
PubMed 21907865Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. doi: 10.1164/rccm.201701-0218PP.
PubMed 28128970You R, Lu W, Shan M, Berlin JM, Samuel EL, Marcano DC, Sun Z, Sikkema WK, Yuan X, Song L, Hendrix AY, Tour JM, Corry DB, Kheradmand F. Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema. Elife. 2015 Oct 5;4:e09623. doi: 10.7554/eLife.09623.
PubMed 26437452Tuder RM, Petrache I. Pathogenesis of chronic obstructive pulmonary disease. J Clin Invest. 2012 Aug;122(8):2749-55. doi: 10.1172/JCI60324. Epub 2012 Aug 1.
PubMed 22850885Green CE, Turner AM. The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD). Respir Res. 2017 Jan 18;18(1):20. doi: 10.1186/s12931-017-0505-1.
PubMed 28100233van Agteren JE, Carson KV, Tiong LU, Smith BJ. Lung volume reduction surgery for diffuse emphysema. Cochrane Database Syst Rev. 2016 Oct 14;10(10):CD001001. doi: 10.1002/14651858.CD001001.pub3.
PubMed 27739074Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008 Oct 9;359(15):1543-54. doi: 10.1056/NEJMoa0805800. Epub 2008 Oct 5.
PubMed 18836213Pauwels RA, Lofdahl CG, Laitinen LA, Schouten JP, Postma DS, Pride NB, Ohlsson SV. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999 Jun 24;340(25):1948-53. doi: 10.1056/NEJM199906243402503.
PubMed 10379018Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE; National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003 May 22;348(21):2059-73. doi: 10.1056/NEJMoa030287. Epub 2003 May 20.
PubMed 12759479Klooster K, ten Hacken NH, Hartman JE, Kerstjens HA, van Rikxoort EM, Slebos DJ. Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation. N Engl J Med. 2015 Dec 10;373(24):2325-35. doi: 10.1056/NEJMoa1507807.
PubMed 26650153Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143.
PubMed 10102814Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, DeBruijn J, Dominici M, Fibbe WE, Gee AP, Gimble JM, Hematti P, Koh MB, LeBlanc K, Martin I, McNiece IK, Mendicino M, Oh S, Ortiz L, Phinney DG, Planat V, Shi Y, Stroncek DF, Viswanathan S, Weiss DJ, Sensebe L. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy. 2016 Feb;18(2):151-9. doi: 10.1016/j.jcyt.2015.11.008. Epub 2015 Dec 23.
PubMed 26724220Bernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013 Oct 3;13(4):392-402. doi: 10.1016/j.stem.2013.09.006.
PubMed 24094322Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008 Sep;8(9):726-36. doi: 10.1038/nri2395.
PubMed 19172693
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Explorative Study for Halting Inflammation in Patients With Emphysema by Administration of Allogeneic Bone Marrow Derived Mesenchymal Stromal Cells.
- ClinicalTrials.gov ID
- NCT04918706
- Acronym / sponsor ID
- HEP study
- Conditions
- Pulmonary Emphysema, Mesenchymal Stromal Cells
- Keywords
- Allogeneic mesenchymal stromal cells, Pulmonary Emphysema, Long volume reduction surgery, Inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Amsterdam UMC, location VUmc
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 1 Jun 2022 (estimated)
- First posted
- 9 Jun 2021 (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: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Bone marrow-derived mesenchymal stromal cells have potential to halt the progressive inflammatory response as indicated by the investigator's pilot study (CCMO NL28562.000.09) .
Objective: To determine whether patients with emphysema develop anti-inflammatory and tissue repair responses by treatment with allogeneic bone marrow-derived mesenchymal stromal cells (MSC) from healthy donors.
Study design: an explorative double-blind, placebo-controlled randomized (2:1) trial in 30 patients with moderate to severe emphysema who are scheduled for two separate sessions for surgical lung volume reduction (LVRS). The study treatment is intravenous allogeneic MSC or placebo treatment in between the first and second surgical session. Randomisation will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to receive placebo) at week 4 and 3 before the second LVRS, and will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to placebo) at week 12 and 11 before the second LVRS.
Main study parameters/endpoints: the study has a co-primary endpoint. First, the difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo. Second, the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2.
Detailed description
Rationale: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Since 25 years, patients with moderate to severe emphysema are treated with inhaled or oral corticosteroids. Currently, consensus is developing that this anti-inflammatory treatment is not effective to halt progression of emphysema. Therefore, emphysema may be classified as steroid-resistant and requires new anti-inflammatory treatment approaches, including cellbased therapies. Bone marrow-derived mesenchymal stromal cells have potential to halt the progressive inflammatory response in various diseases, including steroid-resistant transplant rejection, Crohn's disease and possibly emphysema as indicated by our pilot study (CCMO NL28562.000.09) .
Objective: To determine whether patients with emphysema develop anti-inflammatory and tissue repair responses by treatment with allogeneic bone marrow-derived mesenchymal stromal cells (MSC) from healthy donors.
Study design: an explorative double-blind, placebo-controlled randomized (2:1) trial in 30 patients with moderate to severe emphysema who are scheduled for two separate sessions for surgical lung volume reduction (LVRS). The study treatment is intravenous allogeneic MSC or placebo treatment in between the first and second surgical session. Randomisation will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to receive placebo) at week 4 and 3 before the second LVRS, and will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to placebo) at week 12 and 11 before the second LVRS.
Study population: patients between age 45 and 65; a gradient of emphysema severity towards the lung apex as assessed by CT-derived lung densitometry and equally distributed between left and right lung; FEV1 between 20% and 45% pred; Gas diffusion capacity between 30% and 45% pred. Intervention (if applicable): MSC infusions with cryo-preserved MSC in a dose of 2 x 106 /kg body weight in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg ( at a maximum of 200 x106 MSC per study participant) in a covered bag or NaCl 0.9% with 5% DMSO in a covered bag, both produced in the GMP facility of LUMC.
Main study parameters/endpoints: the study has a co-primary endpoint. First, the difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo. Second, the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: LVRS is a routine procedure for treatment of emphysema and received a positive recommendation from the Cochrane Institute. The dose of MSC has been infused in over 200 patients in LUMC only causing mild side effects like fever and headache, mostly related to DMSO, which is present as a cryoprotectant in the verum. Placebo may also cause fever and headache (DMSO). For the study, additional physical exams will be performed 6 monthly for a period of 3 years after LVRS2 and additional blood sampling specific for the study protocol will be 50ml in total. A heparinized blood sample of 10 ml per sample will be taken: 1) just before the 1st LVRS while patient is under general anaesthesia, 2) just before the 1st MSC iv, 3) just before the 2nd MSC iv, 4) just before the 2nd LVRS while the patient is under general anaesthesia. Discomfort for the patient caused by the experimental treatment will be minimal while there is no reason to assume that hospital admission for the surgery will be prolonged by the cell therapy or placebo. The risks associated with the investigational treatment are low as the reported adverse events in Toetsing Online from previous MSC studies in LUMC show only mild to moderate severity. The risk-benefit analysis is low.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomisation (2:1) will allocate 30 patients to two treatment groups. The first group will receive either 2 x 10^6/kg body weight MSC in a range of 1.5 x 10^6 MSC/ kg to 2.5 x 10^6 MSC/kg (at a maximum of 200 x10^6 MSC per study participant) with 5% DMSO iv or placebo (consisting of a 5% DMSO-solution in isotonic solution) at week 4 and 3 before the second LVRS. The second group will receive either the same dose of 2 x 10^6/kg body weight MSC iv or placebo at week 12 and 11 before the second LVRS.
| Arm | Type | Receives |
|---|---|---|
| MSC week 4 and 3 before LVRS2 | Experimental | Genetic: Allogeneic MSCAllogeneic mesenchymal Stromal cells: 2 x 10^6/kg body weight MSC in a range of 1.5 x 10^6 MSC/ kg to 2.5 x 10^6 MSC/kg (at a maximum of 200 x10^6 MSC per study participant) with 5% DMSO iv |
| Placebo week 4 and 3 before LVRS2 | Placebo comparator | Drug: PlaceboPlacebo: consisting of a 5% DMSO-solution in isotonic solution |
| MSC week 12 and 11 before LVRS2 | Experimental | Genetic: Allogeneic MSCAllogeneic mesenchymal Stromal cells: 2 x 10^6/kg body weight MSC in a range of 1.5 x 10^6 MSC/ kg to 2.5 x 10^6 MSC/kg (at a maximum of 200 x10^6 MSC per study participant) with 5% DMSO iv |
| Placebo week 12 and 11 before LVRS2 | Placebo comparator | Drug: PlaceboPlacebo: consisting of a 5% DMSO-solution in isotonic solution |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial;
- Scheduled for lung volume reduction surgery for emphysema as determined by a referring chest physician;
- Pre-bronchodilator measured FEV1 between 20% and 45% predicted; TLCO between 30% and 45% pred.; RV/TLC ≥ 50%;
- Patients in a stable clinical condition.
Key exclusion criteria (7 listed)
- Significant cardiac failure;
- Active smoking, or < 6 months smoking cessation;
- Failure to complete pulmonary rehab program before randomization
- Women of child bearing potential;
- Any cancer treated in the previous 5 years;
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 |
|---|---|---|
| Allogeneic MSCThese MSCs will originate from bone marrow that will be aspirated from healthy volunteer donors screened by a trained physician of the center for stem cell therapy of LUMC | Genetic | MSC week 12 and 11 before LVRS2, MSC week 4 and 3 before LVRS2 |
| PlaceboThe placebo will be an equivalent volume NaCl 0,9% and DMSO 5% | Drug | Placebo week 12 and 11 before LVRS2, Placebo week 4 and 3 before LVRS2 |
Primary outcome
Difference in expression of CD31
Time frame: Within one year after the last study patient had its second lung surgical procedure
The difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo
The difference between MSC and placebo treatment in change in CO diffusion capacity
Time frame: 1 year after the last CO diffusion measurement
The difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2
5 secondary outcomes
The differences in expression of Surfactant Protein-C expression by alveolar type II cells in lung tissue obtained from study patients treated with placebo or MSC.
Time frame: Within one year after the last study patient had its second lung surgical procedure
The difference in immunostaining of various leukocytes in resected lung tissue, including T lymphocytes, B lymphocytes, macrophages and neutrophils obtained from study patients treated with placebo or MSC.
Time frame: Within one year after the last study patient had its second lung surgical procedure
The difference in shear stress responses, expressed as % elongation of 100 cells, of isolated pMVECs ex vivo obtained from study patients treated with placebo or MSC.
Time frame: Within one year after the last study patient had its second lung surgical procedure
The difference in endothelial microparticles concentration and concentration of immunological markers in blood samples from study patients treated with placebo or MSC.
Time frame: Within one year after the last study patient had its second lung surgical procedure
The correlation between arterial pO2 or gas transfer value TLCO (measured as standard of care) and the outcome of the primary objective of the study for patients treated with MSC or placebo.
Time frame: at 12 weeks, as well as after 6 and 12 months, after discharge of admission for LVRS2
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2021.
- Background: PubMed 22029986Mitzner W. Emphysema--a disease of small airways or lung parenchyma? N Engl J Med. 2011 Oct 27;365(17):1637-9. doi: 10.1056/NEJMe1110635. No abstract available.
- Background: PubMed 21907865Brusselle GG, Joos GF, Bracke KR. New insights into the immunology of chronic obstructive pulmonary disease. Lancet. 2011 Sep 10;378(9795):1015-26. doi: 10.1016/S0140-6736(11)60988-4.
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- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic MSC in people with Pulmonary Emphysema and Mesenchymal Stromal Cells, run by Leiden University Medical Center at 1 site in Netherlands.
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 7 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: status not confirmed, as of the sponsor's last update on 9 Jun 2021. 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 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jan Stolk, MD (+31715262950, jstolk@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in expression of CD31 (time frame: Within one year after the last study patient had its second lung surgical procedure). The study lists 2 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 NCT04918706, which also lists 39 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 9 Jun 2021; AzTrials last refreshed its copy on 31 Oct 2026.