An explorative study for halting inflammation in patients with emphysema by administration of allogeneic bone marrow derived mesenchymal stromal cells.

An explorative study for halting inflammation in patients with emphysema by administration of allogeneic bone marrow derived mesenchymal stromal cells. - HEP study

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON48907

Enrollment

Registered

2018-02-06

Start date

2018-06-21

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD stretched lungs

Interventions

Patients undergo routine treatment for two lung-reducing operations (LVRS) with an interval of approximately 5 months. Patient will be randomized (2 : 1

MSC : placebo) for intravenous administration of a dose of 2 x 10> 6 MSC / kg body weight or placebo. These cells are administered prior to the second lung reduction operation, depending on the ran

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: 1.Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial. 2.Males or females between 45 and 65 years of age; 3.Emphysema as reported by a radiologist present in CT images of the lung; gradient of emphysema severity towards the lung apex as assessed by CT-derived lung densitometry by Pulmo CMS software (Medis, NL) and equally distributed between left and right lung. 4. Pre bronchodilator value measured FEV1 between 20% and 45% predicted; TLCO between 30% and 45% pred.; RV/TLC > 0.5. 5. Patients in a stable clinical condition.

Exclusion criteria

Exclusion criteria: 1. Significant cardiac failure; 2. active smoking, or

Design outcomes

Primary

Measure	Time frame
Co-primary outcome parameters are: (1) to detect the difference in expression of PECAM-1 (CD31) on pulmonary microvascular endothelial cells (pMVECs) per micrometer alveolar septum present in lung tissue harvested from patients at LVRS 2 after 4 weeks of treatment with allogeneic MSC or placebo and (2) to measure the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following the second LVRS.	—

Measure

Time frame

Co-primary outcome parameters are: (1) to detect the difference in expression of PECAM-1 (CD31) on pulmonary microvascular endothelial cells (pMVECs) per micrometer alveolar septum present in lung tissue harvested from patients at LVRS 2 after 4 weeks of treatment with allogeneic MSC or placebo and (2) to measure the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following the second LVRS.

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Secondary

Measure	Time frame
1. to demonstrate safety of i.v. administration of MSC to patients with moderate to severe emphysema as determined by WHO safety criteria. 2. the difference in expression of CD31 on pMVECs per micrometer alveolar septum present in lung tissue harvested from patients at lung surgery 2 (LVRS2) treated with placebo and patients treated with allogeneic MSC, recieved at 12 and 11 weeks prior to the surgery. 3. the difference in the number of CD3+ and CD4+ T-cells present in lung tissue harvested from LVRS 2 measured after administration of placebo or MSC at the two different time points as described in the protocol. 4. As in 2 and 3, but then the difference of these markers between LVRS 2 and 1 within patients. 5. the difference in the number of type II alveolar cells present in lung tissue harvested from LVRS 2 from patients after 4 or 12 weeks of treatment with placebo and patients treated with MSC. 6. The difference in shear stress response and level of apoptosis of isolated pMVECs from LVRS 1 and 2 of patients treated with either MSC or placebo 7. The difference in Cytosplore response (explained below) of isolated immune cells from LVRS 1 and 2 of patients treated with either MSC or placebo. 8. To demonstrate a statistical significant correlation between arterial pO2 or carbon monoxide gas exchange capacity at 12, 26 and 52 weeks after discharge of admission for LVRS 2 and the outcome of the primary objective of the study for patients treated with MSC.	—

Measure

Time frame

1. to demonstrate safety of i.v. administration of MSC to patients with moderate to severe emphysema as determined by WHO safety criteria. 2. the difference in expression of CD31 on pMVECs per micrometer alveolar septum present in lung tissue harvested from patients at lung surgery 2 (LVRS2) treated with placebo and patients treated with allogeneic MSC, recieved at 12 and 11 weeks prior to the surgery. 3. the difference in the number of CD3+ and CD4+ T-cells present in lung tissue harvested from LVRS 2 measured after administration of placebo or MSC at the two different time points as described in the protocol. 4. As in 2 and 3, but then the difference of these markers between LVRS 2 and 1 within patients. 5. the difference in the number of type II alveolar cells present in lung tissue harvested from LVRS 2 from patients after 4 or 12 weeks of treatment with placebo and patients treated with MSC. 6. The difference in shear stress response and level of apoptosis of isolated pMVECs from LVRS 1 and 2 of patients treated with either MSC or placebo 7. The difference in Cytosplore response (explained below) of isolated immune cells from LVRS 1 and 2 of patients treated with either MSC or placebo. 8. To demonstrate a statistical significant correlation between arterial pO2 or carbon monoxide gas exchange capacity at 12, 26 and 52 weeks after discharge of admission for LVRS 2 and the outcome of the primary objective of the study for patients treated with MSC.

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)