Adipose Derived Mesenchymal Cell Treatment in Lungtransplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Danish, Single Centre, Double-blind, Randomized Study Evaluating Allogeneic Adipose Tissue Derived Mesenchymal Stromal Cell Therapy to Reduce Primary Graft Dysfunction After Lung Transplantation

Conditions
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Lung Transplant Rejection

Intervention / Treatment
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* Drug: adipose derived mesenchymal stromal cells
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind placebo-controlled dose titrating study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Infusion of 100 million ASC<br>Infusion of 100 million adipose derived mesenchymal stromal cells from healthy donors | Drug: adipose derived mesenchymal stromal cells<br>* Intravenous infusion of cells<br>* Other names: CSCC_ASC;|
| Active Comparator: Infusion of 200 million ASC<br>Infusion of 200 million adipose derived mesenchymal stromal cells from healthy donors | Drug: adipose derived mesenchymal stromal cells<br>* Intravenous infusion of cells<br>* Other names: CSCC_ASC;|
| Placebo Comparator: Infusion of placebo<br>Infusion of saline | Drug: Saline<br>* Intravenous infusion of saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary graft dysfunction (PDG) | 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 | 3 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kidney glomerular Filtration Rate | Difference in estimated Glomerular Filtration Rate (eGFR)/1,73 m2. Normal > 60 ml/min | 12 weeks after treatment | 
| Inflammatory markers | Differences in C-reactive protein. Normal value < 10mg/ml | through the 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lung transplantation, Rejection, mesenchymal stromal cell, immune modulation, clinical trial, treatment