Adipose Derived Mesenchymal Cell Treatment in Lungtransplantation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Transplant Rejection
• Intervention / Treatment: Drug: adipose derived mesenchymal stromal cells; Drug: Saline

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jens Kastrup, MD Professor; Phone Number: +4535452819; Email: jens.kastrup@regionh.dk
• Study Contact Backup: Name: Abbas A Qayuum, MD; Phone Number: +4535452819; Email: Abbas.Ali.Qayyum@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • 2014 Department of Cardiology, The Heart Centre, University Hospital Rigshospitalet
    • Contact: Jens Kastrup, MD DMSc; Phone Number: +4535452817; Email: jens.kastrup@regionh.dk
    • Principal Investigator: Jens Kastrup, MD DMSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Study Director: Jens Kastrup, MD Professor, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): November 30, 2023
• Study Completion (Anticipated): November 30, 2024

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): July 16, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: treatment; Rejection; clinical trial; lung transplantation; immune modulation; mesenchymal stromal cell
• Other Study ID Numbers: ASC Lungtransplantation

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are open for collaboration with external research groups, but have no presently plans
• IPD Sharing Time Frame: When the study is finalized and published
• IPD Sharing Access Criteria: Relevant documented use of data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No