Development of mesenchymal stromal cell therapy to halt the progression of emphysema.
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
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.
Background summary
For patients with pulmonary emphysema there are no effective medications that
can stop disease progression, even if they quit smoking. In recent years,
success has been achieved with lungvolume reduction for pulmonary emphysema. By
placing valves in airways, the patient becomes less short of breath. About 10%
of all emphysema patients are eligible for treatment with valves. The
alternative to another 10-20% of all emphysema patients is a surgical reduction
of bullous parts in the lung, usually located in the top of the upper lung
lobes of both lungs. If no more than 30% of all emphysema patients can be
treated, this suggests that improvement of current emphysema treatment is
highly needed.
Study objective
Development of mesenchymal stromal cell therapy to halt the progression of
emphysema.
Study design
Double blind, placebo-controlled, randomized explorative study with allogeneic
mesenchymal stromal cells cultured from bone marrow healthy donors.
Intervention
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 randomization result: 4 and 3 weeks
before or 12 and 11 weeks prior to the second operation. Three months after
discharge from the second LVRS, patients will be seen at the Outpatient Clinic
of the Pulmonary Department of LUMC and at 6 monthly intervals for a total of 3
years. During each visit CO diffusion capacity will be measured. In addition,
symptoms wil be recorded and phisical exam will be performed.
Study burden and risks
MSC is currently being investigated as cell therapy for a variaty of
inflammatory diseases and agreement amongst clinical scientists is developing
that MSC treatment is therapeutic because MSC have the ability to migrate to
inflammatory sites to inhibit the local inflammatory response. It is remarkable
that MSC appears safe for almost all diseases tested. As with all new medical
treatments, it is important to accurately designed studies to find the right
dose to identify an effect on relevant outcome measures. We have the strong
opinion that MSC effects should first be analyzed in lung tissue of emphysema
patients. Only after insight has been obtained in the anti-inflammatory effect
by MSC in the lung tissue of emphysema patients, it will become clear to select
the proper outcome parameters for future larger clinical trials. To date, it is
not yet clear which outcome measures are most appropriate.
By using routine lungvolume-reducing surgery for treating emphysema, the burden
of MSC treatment can be confined to a rather limited number of patients to
investigate whether MSC cause anti-inflammatory effects in pulmonary emphysema.
Albinusdreef 2
Leiden 2300 ZA
NL
Albinusdreef 2
Leiden 2300 ZA
NL
Listed location countries
Age
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
1. Significant cardiac failure;
2. active smoking, or < 6 months smoking cessation;
3. or failure to complete pulmonary rehab program before randomization;
4. women of child bearing potential;
5. any cancer treated in the previous 5 years;
6. women of child-bearing potential not using adequate contraception;
7. any other condition of the patient that the clinical investigator deemed
harmful for study participation.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001853-15-NL |
| CCMO | NL63261.000.17 |