Multicenter Analysis of Efficacy and Outcomes of Extracorporeal Photopheresis as Treatment of Chronic Lung Allograft Dysfunction

NCT04792294 | Unknown FDA Device

• 1 other identifier: 1541/2020
• Study Type: observational
• Target: 800
• Locations: 0 countries
• Sites: N/A

Brief Summary

Lung transplantation is an established therapy for end-stage lung disease such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and pulmonary hypertension. However, Chronic Lung Allograft Dysfunction (CLAD) is a major cause of morbidity and mortality in long-term survivors. The 5-year survival rate is reported to be 50%, which is considerably inferior compared to other solid organ transplantation. In addition, the financial burden of CLAD (around 80.000 euro/year for a patient with CLAD) is considerable. No curative therapy is available yet. To date, the two most effective treatment are azithromycin and extracorporeal photopheresis. Azithromycin is used as first-line treatment and it is effective in stopping FEV1 decline, however its effects are only limited to a set of patients. ECP can be used as second-line treatment in patients unresponsive to azithromycin. ECP has been firstly developed for treatment of cutaneous T cell lymphomas and later used in a variety of other indications including solid organ transplantation. The process starts with leukapheresis, followed by incubation of the isolated cells with 8-methoxypsoralen (8-MOP) and subsequent activation of 8-MOP with ultraviolet A radiation. At the end, the cells are reinfused into the patient. 8-MOP is a biologically inert substance, but in the presence of UVA light it cross-links DNA by forming covalent bonds with pyrimidine bases and causes apoptosis. ECP is effective in the palliative treatment of cutaneous T-cell lymphoma but its effectiveness was also shown in several other T-cell-mediated diseases, particularly in the treatment and prevention of acute and chronic graft-versus-host disease. In depth knowledge on the mechanisms whereby ECP manipulates the immune system are still unclear. Most of the experimental studies have been performed in murine models of GvHD. Apoptotic cells isolated during ECP treatment have the potential to induce IL-10 secretion, reduce dendritic cells activation and increase percentage of Tregs. In addition, ECP reduces the production of IL-6 and TNF-α and increases TGF-β production. In lung transplantation, ECP treatment is used as second-line treatment of CLAD and it has the potential to stabilize lung function decline and to improve long-term graft. According to the published literature, however, approximately 30 to 40% of treated recipients did not profit from ECP. Greer and colleagues found that RAS patients as well as rapid lung function decliners showed lower rate of response and worse long-term outcomes. On the contrary in a more recent analysis only BOS diagnosis was associated with better outcomes. A single prospective interventional study was published by our group and it confirmed results from other previous retrospective analysis. Up to now, no clear predictors for response have been identified yet.

Conditions

Lung Transplant Rejection

Outcome Measures

Primary Outcomes (1)

• Change in forced expiratory value in 1 second at 3 months after start of extracorporeal photopheresis

  Percentage change in FEV1 within 3 months after start of extracorporeal photopheresis

  3 months

Secondary Outcomes (6)

• change in maximal expiratory flow (50%) at 3 months after start of extracorporeal photopheresis

  3 months

• Change in forced expiratory value in 1 second/dorced vital capacity ratio at 3 months after start of extracorporeal photopheresis

  3 months

• Change in total lung capacity at 3 months after start of extracorporeal photopheresis

  3 months

• Patients' survival

  Within 5 years from start of extracorporeal photopheresis

• Graft survival

  Within 5 years from start of extracorporeal photopheresis

Study Arms (1)

Lung transplant recipients with chronic lung allograft dysfunction

Lung transplant recipients with chronic lung allograft dysfunction, who underwent extracorporeal photopheresis

Device: Extracorporeal photopheresis

Interventions

Extracorporeal photopheresis DEVICE

ECP can be used as second-line treatment in patients unresponsive to azithromycin. ECP has been firstly developed for treatment of cutaneous T cell lymphomas and later used in a variety of other indications including solid organ transplantation. The process starts with leukapheresis, followed by incubation of the isolated cells with 8-methoxypsoralen (8-MOP) and subsequent activation of 8-MOP with ultraviolet A radiation. At the end, the cells are reinfused into the patient. 8-MOP is a biologically inert substance, but in the presence of UVA light it cross-links DNA by forming covalent bonds with pyrimidine bases and causes apoptosis.

Lung transplant recipients with chronic lung allograft dysfunction

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Lung transplant recipients with chronic lung allograft dysfunction who received extracorporeal photopheresis as treatment

You may qualify if:

• Diagnosis of CLAD Adult transplant recipients (\>18 years)

You may not qualify if:

• ECP for other diagnosis Recipients of multi-organ transplantation Recipients of single lung transplantation

Sponsors & Collaborators

• Medical University of Vienna: lead

MeSH Terms

Interventions

Photopheresis

Intervention Hierarchy (Ancestors)

PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 10, 2021
• Study Start: January 1, 2005
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 10, 2021

Record last verified: 2021-03