Lung Transplant Rejection
Conditions
Keywords
lung transplantation, Rejection, mesenchymal stromal cell, immune modulation, clinical trial, treatment
Brief summary
To investigate safety of treatment with allogeneic adipose tissue-derived mesenchymal stromal cells (ASCs) in patients undergoing lung transplantation, to evaluate whether the treatment can reduce host immunological reaction towards the graft, and to reduce the ischemic reperfusion-injury after transplantation.
Detailed description
The emerging field of stem cell therapy holds promise of treating a variety of diseases. Especially the mesenchymal stromal cells from bone marrow (BMSCs) or adipose tissue (ASCs) have proven their potential for regenerative therapy in patients with ischemic heart disease. Both of these cell types have putative immunomodulatory properties, as they have demonstrated to actively suppress the immune system and hereby evade recognition. This knowledge will be transferred into studies in the ischemic reperfusion-injury/primary lung graft dysfunction in lung transplantation, and in suppressing the initial host immunological response towards the transplanted lung where a high degree of immunological and inflammatory activity is involved. We will conduct a clinical trial in which patients receiving lung transplantation will be randomized to either placebo or treatment with allogeneic MSCs from adipose tissue. The aim is to assess the impact of MSCs on primary graft dysfunction. The perspective is that this new information can be of pivotal importance and potentially be a paradigm shift for the clinical problems seen in the first period after lung transplantation and reduce the long-term graft rejection and dysfunction.
Interventions
DRUGadipose derived mesenchymal stromal cells
Intravenous infusion of cells
DRUGSaline
Intravenous infusion of saline
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Double-blind placebo-controlled dose titrating study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female lung recipients 18-70 years of age undergoing primary double (including size reduction) lung transplantation. * Patient willing and capable of giving written informed consent for study participation and anticipated to be able to participate in the study for 3 months.
Exclusion criteria
* Recipients of multi-organ transplant, and or previously transplanted with any solid organ, including previous lung transplantation. * Patients scheduled for single lung transplantation. * Patients in need of acute transplantation e.g. patients on urgent call for transplantation and patients on respirator or on extra corporal membrane oxygenation (ECMO) treatment at time of transplantation. * Patients that based on crossmatch prior to transplantation have need for additional immunosuppressive treatment * Donor lung cold ischemic time \> 12 hours. * Patients with platelet count \< 50,000/mm3 at the evaluation before transplantation. * Patients who are unlikely to comply with the study requirements. * Patient unable to participate in the study for the full study period * Patients with any past (within the past 3-5 years) or present malignancy (other than excised basal cell carcinoma). * Females capable of becoming pregnant must have a negative pregnancy test prior to transplantation. After inclusion, they must use contraceptives for 2 months following the given stem cell treatment. The pill, spiral, depot injection of progesterone, sub-dermal implantation, hormonal vaginal ring and transdermal patch regarded as safe contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pulmonary graft dysfunction (PDG) | 3 days after treatment | Difference in presence or not presence of Primary graft dysfunction (PGD) after transplantation in ASC treated patients compared to controls. Primary graft dysfunction is defined, according to the International Society for Heart and Lung Transplantation (ISHLT), as presence of both pulmonary infiltrates and hypoxemia occurring within the first 72 hours after transplantation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney glomerular Filtration Rate | 12 weeks after treatment | Difference in estimated Glomerular Filtration Rate (eGFR)/1,73 m2. Normal \> 60 ml/min |
| Inflammatory markers | through the 12 weeks | Differences in C-reactive protein. Normal value \< 10mg/ml |
Countries
Denmark
Contacts
Primary ContactJens Kastrup, MD Professor
Backup ContactAbbas A Qayuum, MD
Outcome results
None listed