Aerosol Liposomal Cyclosporine for Chronic Rejection in Lung Transplant Recipients

• ClinicalTrials.gov Identifier: NCT01650545
• Recruitment Status: Completed
• First Posted: July 26, 2012
• Results First Posted: October 25, 2017
• Last Update Posted: March 2, 2018
• Sponsor: University of Maryland, College Park
• Information provided by (Responsible Party): Aldo Iacono, University of Maryland, College Park

Study Description

Brief Summary:

This is a single-center pilot study to investigate the efficacy and safety of aerosolized liposomal cyclosporine A in the treatment of chronic rejection in lung transplant recipients with bronchiolitis obliterans syndrome (BOS).

The primary objective is to evaluate the efficacy of liposomal cyclosporine A in the treatment of chronic rejection. Pulmonary function and changes in BOS grade are the primary end points.

Condition or disease	Intervention/treatment	Phase
Disorder Related to Lung Transplantation; Bronchiolitis Obliterans; Decreased Immunologic Activity; Chronic Rejection of Lung Transplant	Drug: Liposomal aerosol cyclosporine; Other: standard immune suppression, oral	Phase 1; Phase 2

Detailed Description:

This is a randomized single-center pilot study to investigate the efficacy and safety of aerosolized liposomal cyclosporine A (L-CsA) in the treatment of chronic rejection in lung transplant recipients with Grade 1 or 2 BOS.

The primary endpoints will include:

• Improvement or stabilization of pulmonary function test (FEV1) from baseline
• Stabilization of histology (no deterioration from baseline)
• Safety of the preparation

The secondary endpoints will include:

• Pharmacokinetics and distribution of CsA in blood -
• Change in cytokine levels from BAL specimens.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open Label
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Demonstrate Efficacy and Safety of Aerosol Liposomal Cyclosporine (L-CsA) in the Treatment of Bronchiolitis Obliterans Syndrome After Lung Transplantation
• Actual Study Start Date: July 2012
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Liposomal Aerosol Cyclosporine; Arm 1) Aerosol liposomal cyclosporine Open label randomized trial using experimental inhalational therapy with liposomal aerosol cyclosporine in addition to standard immune suppression (tacrolimus , mycophenolate mofetil and prednisone) for 6 month duration at inhalational doses (5mg and 10 mg bid), to be defined by transplant type respectively (single, double lung transplant )	Drug: Liposomal aerosol cyclosporine; inhaled form of immune suppression; Other Name: cyclosporine; Other: standard immune suppression, oral; conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin; Other Names: tacrolimus; rapamycin; sirolimus
Active Comparator: Conventional oral immune suppression; Arm 2) Standard immune suppression consisting of typical oral immune suppression for lung transplant recipients typically tacrolimus, mycophenolate mofetil and prednisone. Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone rapamycin described in the subsequent section as well.	Other: standard immune suppression, oral; conventional drug Conventrional oral immune suppression as standard of care thus consists of tacrolimus, mycophenolate mofetil prednisone and rapamycin; Other Names: tacrolimus; rapamycin; sirolimus

Outcome Measures

Primary Outcome Measures :

1. Number Of Participants With Chronic Rejection Who Met Primary Combined End-point [ Time Frame: approximately 1 year ]
   Treatment failure defined as: BOS progression (> 20% decline lung function), re-transplant, or death

Secondary Outcome Measures :

1. Cytokine Analysis From BAL Fluid in Lung [ Time Frame: baseline to approximately 1 year ]
   Multiple cytokines were assessed as markers of lung inflammation that may be used in addition to biopsy data, collected per patient as clinically indicated during the follow-up interval. Values are reported as mean change from baseline in each group, per week
2. Overall Survival at 5 Years Follow-up [ Time Frame: 5 years ]
   Number of participants surviving at 5 year follow-up

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Chronic rejection

1. Bronchiolitis obliterans diagnosed by bronchiolitis obliterans syndrome and > 20% decline from the individual patient's best FEV1 is observed
2. Recipient of a double or single lung transplant
3. Receiving immunosuppressive treatment according to institutional standards

Exclusion criteria:

1. Active invasive bacterial, viral or fungal infection
2. Current mechanical ventilation
3. Pregnant or breast-feeding woman
4. Known hypersensitivity to cyclosporine A
5. Serum creatinine value of more than 265 μmol/L (3 mg/dL) or chronic dialysis
6. Receipt of an investigational drug as part of a clinical trial

Contacts and Locations

Locations

United States, Maryland

University of Maryland Medical Center

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, College Park

Investigators

• Principal Investigator: Aldo T Iacono, MD; University of Maryland, College Park

More Information

Publications:

Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50.

• Responsible Party: Aldo Iacono, Professor of Medicine Medical Director of Lung Transplantation, University of Maryland, College Park
• ClinicalTrials.gov Identifier: NCT01650545
• Other Study ID Numbers: HP-00049596
• First Posted: July 26, 2012
• Results First Posted: October 25, 2017
• Last Update Posted: March 2, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Aldo Iacono, University of Maryland, College Park:

case-control study; aerosolized liposomal cyclosporine A; bronchiolitis obliterans syndrome; Lung Transplantation; Lung function

Additional relevant MeSH terms:

Bronchiolitis; Bronchiolitis Obliterans; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Infections; Cyclosporine; Sirolimus; Tacrolimus; Cyclosporins; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents