Dry Powder Inhalation of Cyclosporine A in Lung Transplant Patients With Bronchiolitis Obliterans Syndrome - Full Text View

Sponsor:	University Medical Centre Groningen
Information provided by:	University Medical Centre Groningen
ClinicalTrials.gov Identifier:	NCT00378677

Purpose

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.

Condition	Intervention	Phase
Lung Transplantation Bronchiolitis Obliterans	Drug: Cyclosporine A dry powder inhalation (Drug)	Phase 0

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pilot Study of Cyclosporine A Dry Powder Inhalation in Lung Transplant Patients With Bronchiolitis Obliterans Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Lung Transplantation

Drug Information available for: Cyclosporine Cyclosporin

U.S. FDA Resources

Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:

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 Outcome Measures:

Kidney function (GFR and serum creat)

Estimated Enrollment:	7
Study Start Date:	February 2007

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378677

Contacts

Contact: Wim Van Der Bij, MD, PhD	+31 50 3616161
Contact: Huib Kerstjens, MD, PhD	+31 50 3616161

Locations

Netherlands
University Medical Center Groningen	Recruiting
Groningen, Netherlands
Principal Investigator: Wim Van Der Bij, Md, PhD

Sponsors and Collaborators

University Medical Centre Groningen

Investigators

Principal Investigator:

Gerrit Zijlstra, Pharmacist

University Medical Centre Groningen

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00378677 History of Changes
Other Study ID Numbers:	CSA-DPI
Study First Received:	September 20, 2006
Last Updated:	February 6, 2007
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by University Medical Centre Groningen:

Powder inhalation
Side effects
Nephrotoxicity

Calcineurin inhibitor
Bronchiolitis obliterans syndrome
Forced Expiratory Volume

Additional relevant MeSH terms:

Respiratory Aspiration
Bronchiolitis
Bronchiolitis Obliterans
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Bronchitis
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Cyclosporins

Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on February 09, 2012