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

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

Status

UNKNOWN

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00378677

Enrollment

Registered

2006-09-21

Start date

2007-02-28

Completion date

Unknown

Last updated

2007-02-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bronchiolitis Obliterans, Lung Transplantation

Keywords

Powder inhalation, Side effects, Nephrotoxicity, Calcineurin inhibitor, Bronchiolitis obliterans syndrome, Forced Expiratory Volume

Brief 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.

Detailed 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.

Interventions

DRUGCyclosporine A dry powder inhalation (Drug)

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Change in Forced Expiratory Volume in 1 second before and after intervention	—
Amount of lung deposition of cyclosporine A	—
Systemic uptake of Cyclosporine A	—

Secondary

Measure	Time frame
Kidney function (GFR and serum creat)	—

Countries

Netherlands

Contacts

Primary ContactWim Van Der Bij, MD, PhD

+31 50 3616161

Backup ContactHuib Kerstjens, MD, PhD