Aridol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in COPD

Lung Diseases, Obstructive Clinical Trial

Official title:

A Phase II Study to Investigate Mannitol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00117182
• Other study ID #: DPM-COPD-201
• Status: Completed
• Phase: Phase 2
• First received: June 30, 2005
• Last updated: April 18, 2016
• Start date: July 2005
• Est. completion date: August 2006

Study information

• Verified date: April 2016
• Source: Pharmaxis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether the Aridol (mannitol) challenge test can predict response to treatment with inhaled corticosteroids in COPD subjects. Subjects will undergo an Aridol test and then 3 months of treatment with inhaled corticosteroids. The effect on lung function and quality of life will then be measured and correlated with the Aridol test result.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 80 Years

Eligibility

Inclusion Criteria:

• Diagnosis of COPD (history, spirometry, symptoms including chronic cough and/or shortness of breath that is worse on exertion and/or excess sputum production)

• Aged 45 - 80 years

• Have pre-bronchodilator FEV1 > 1.4 litres and at least 60% of predicted for height, age and gender and a post-bronchodilator FEV1 <80% of predicted for height, age and gender

• Post-bronchodilator FEV1/FVC < 70 %

• = 10 pack years smoking history

• As determined by the investigator, are capable and willing to:

• perform all of the techniques necessary to measure lung function;

• administer the dry powder mannitol.

• Are capable of, and have given informed consent to, participating in this study in accordance with local regulations.

• The subject must be in stable clinical condition at the time of, and for a period of 14 days prior to, their recruitment into the study. Stable clinical condition is defined as lack of:

• change in sputum production (volume, colour, consistency);

• increased cough;

• worsening dyspnoea;

• increased malaise, fatigue or lethargy;

• reduction in exercise tolerance;

• fever;

• antibiotic treatment (for respiratory infection).

Exclusion Criteria:

• Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.

• Subjects receiving treatment with inhaled corticosteroids (including combination therapies, e.g. Seretide®, Symbicort®) or oral corticosteroids within the last 6 weeks.

• Subjects who have had an exacerbation or a chest infection within the 2 weeks prior to the study.

• Subjects receiving antibiotic treatment for respiratory infection.

• Known diagnosis of asthma or allergic rhinitis.

• Myocardial infarction in the six months prior to enrolment.

• Cerebral vascular accident in the six months prior to enrolment.

• Ocular surgery in the three months prior to enrolment.

• Abdominal surgery in the three months prior to enrolment.

• Active tuberculosis (TB).

• Lung cancer or any other malignancies, which are considered by the investigator as a contraindication to participating in the study.

• Lung disease other than COPD (e.g. bronchiectasis).

• Uncontrolled insulin-dependant or non-insulin dependant diabetes, i.e. >10% HbA1c.

• Female subjects of reproductive capability, not using a reliable form of contraception

• Inability to obtain informed consent from the subject or subject's authorised representative.

• Subjects who have participated in another investigative drug study parallel to, or within 4 weeks of, study entry.

• Known intolerance to mannitol.

• Uncontrolled hypertension - systolic blood pressure (BP) > 200 mmHg and or diastolic BP > 100 mmHg.

• Planned pulmonary rehabilitation.

• Have had major abdominal, chest or brain surgery in the three months prior to enrolment.

• Have known cerebral, aortic or abdominal aneurysm.

Study Design

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

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Obstructive

Intervention

Drug:
• Dry powder mannitol

• Budesonide 400mcg administered via turbuhaler

• Ipratropium bromide 80mcg

• Salbutamol 400mcg

Locations

Country	Name	City	State
Australia	Wesley Medical Centre	Auchenflower	Queensland
Australia	Flinders University	Bedford Park	South Australia
Australia	Brisbane South Clinical Clinical Research Centre	Brisbane	Queensland
Australia	Peninsula Chest Clinic	Frankston	Victoria
Australia	The rooms of Dr Chris Steinfort	Geelong	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Mount Medical Centre	Perth	Western Australia
Australia	Inala Health Centre	PO BOx 52, Inala	Queensland
Australia	Rosebud Medical Centre	Rosebud	Victoria
Australia	Respiratory Clinic	Sydney	New South Wales
Australia	Respiratory Research Foundation Clinical Trial Centre	Toorak Gardens	South Australia
Australia	Peninsula Medical Centre	Umina	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Pharmaxis

Country where clinical trial is conducted

Australia, 

References & Publications (5)

Anderson SD, Brannan J, Spring J, Spalding N, Rodwell LT, Chan K, Gonda I, Walsh A, Clark AR. A new method for bronchial-provocation testing in asthmatic subjects using a dry powder of mannitol. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):758-65. — View Citation

Brannan JD, Koskela H, Anderson SD, Chan HK. Budesonide reduces sensitivity and reactivity to inhaled mannitol in asthmatic subjects. Respirology. 2002 Mar;7(1):37-44. — View Citation

Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA. Prednisolone response in patients with chronic obstructive pulmonary disease: results from the ISOLDE study. Thorax. 2003 Aug;58(8):654-8. — View Citation

Koskela HO, Hyvärinen L, Brannan JD, Chan HK, Anderson SD. Sensitivity and validity of three bronchial provocation tests to demonstrate the effect of inhaled corticosteroids in asthma. Chest. 2003 Oct;124(4):1341-9. — View Citation

Leuppi JD, Tandjung R, Anderson SD, Stolz D, Brutsche MH, Bingisser R, Perruchoud AP, Surber C, Knoblauch A, Andersson M, Greiff L, Chan HK, Tamm M. Prediction of treatment-response to inhaled corticosteroids by mannitol-challenge test in COPD. A proof of concept. Pulm Pharmacol Ther. 2005;18(2):83-8. Epub 2004 Dec 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced expiratory volume in one second (FEV1)
Secondary	Response dose ratio (RDR)
Secondary	Dose of provoking stimulus causing a 15%, 12% or 10% fall in FEV1 (PD15, PD12, PD10)
Secondary	Lung function values
Secondary	Quality of life assessed by St. George's Respiratory Questionnaire (SGRQ)- total score
Secondary	COPD clinical control scores (CCQ)
Secondary	Exacerbation frequency
Secondary	Days on antibiotics
Secondary	Days off work or days unable to carry out normal activities
Secondary	Reversibility of airflow obstruction