Dry Powder Inhalation of Cyclosporine A in Lung Transplant Patients With Bronchiolitis Obliterans Syndrome

Lung Transplantation Clinical Trial

Official title:

Pilot Study of Cyclosporine A Dry Powder Inhalation in Lung Transplant Patients With Bronchiolitis Obliterans Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00378677
• Other study ID #: CSA-DPI
• Status: Recruiting
• Phase: Phase 0
• First received: September 20, 2006
• Last updated: February 6, 2007
• Start date: February 2007

Study information

• Verified date: February 2007
• Source: University Medical Center Groningen
• Contact: Wim Van Der Bij, MD, PhD
• Phone: +31 50 3616161
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate whether dry powder inhalation of Cyclosporine A is beneficial in lung transplant patients with Bronchiolitis Obliterans Syndrome. For patients suffering from this syndrome often no therapeutic options are available. Furthermore, the side effects of the maintenance therapy leaves no room for dose increments. The hypothesis for this trial is that when Cyclosporine A is administered locally (in the lungs) chronic rejection can be treated more effectively without extra systemic side effects.

Description:

Because calcineurin inhibitors are not completely effective in a full prevention of acute rejection and the corresponding chronic disfunction of the transplanted organ (Bronchiolitis Obliterans Syndrome, BOS) a rejection risc remains. To effectively treat BOS high doses of calcineurin inhibitors are necessary. On the other hand these high doses lead te serious side effects. The search for a balance between effectiveness and side effects leads to dose adjustments. Ultimately, chronic rejection is unstoppable.

In order to treat chronic rejection higher doses of calcineurin inhibitors are not a therapeutic option. The only option to reach a high dose in the target organ without extra systemic side effects would be inhalation. Indeed, this has been extensively investigated at the University of Pittsburgh (lead investigator Iacono).

The intervention in the Pittsburgh trials existed of nebulization of Cyclosporine in propylene glycol with pretreatment of nebulization of lidocaine/albuterol in order to make the inhalation tolerable.

The investigational drug in this trial consists of dry powder inhalation of a sugar-glass based solid dispersion containing cyclosporine A. The effectiveness is measured by comparing the Forced Expiratory Volume in 1 second (FEV1) before and after the intervention.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed Informed Consent

• Primary lung transplant

• Tacrolimus as maintenance therapy

• Bronchiolitis Obliterans Syndrome stages 1 - 3: FEV1<80% of baseline

• At least 3 months after last usual BOS intervention

• Declining FEV1 after last usual BOS intervention

Exclusion Criteria:

• Cyclosporine as maintenance therapy

• Bronchiolitis Obliterans Syndrome 0: FEV1>80%

• Renal failure: Glomerular Filtration Rate < 30 ml/min

• Chronic airway infections

• Clinical stability

• Pregnancy

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Lung Transplantation

Intervention

Drug:
• Cyclosporine A dry powder inhalation (Drug)

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Forced Expiratory Volume in 1 second before and after intervention
Primary	Amount of lung deposition of cyclosporine A
Primary	Systemic uptake of Cyclosporine A
Secondary	Kidney function (GFR and serum creat)