Aridol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease (COPD)

Condition(s) targeted: Lung Diseases, Obstructive

Intervention: Dry powder mannitol (Drug); Budesonide 400mcg administered via turbuhaler (Drug); Ipratropium bromide 80mcg (Drug); Salbutamol 400mcg (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Pharmaxis

Official(s) and/or principal investigator(s):
Alvin Ing, MBBS, Principal Investigator, Affiliation: Bankstown Hospital
Martin Coffey, MBBS, Principal Investigator, Affiliation: Rosebud Medical Centre
David Langton, MBBS, Principal Investigator, Affiliation: Peninsula Chest Clinic, Frankston
Chris Steinfort, MBBS, Principal Investigator, Affiliation: The Rooms of Dr Steinfort, Geelong
Trevor WIlliams, MBBS, Principal Investigator, Affiliation: The Alfred Hospital, Melbourne
Peter Frith, MBBS, Principal Investigator, Affiliation: Flinders Medical Centre
Michael Chia, MBBS, Principal Investigator, Affiliation: Respiratory Research Foundation, Toorak Gardens
Maureen McKeirnan, MBBS, Principal Investigator, Affiliation: Brisbane South Medical Centre
Fred de Looze, MBBS, Principal Investigator, Affiliation: Centre for General Practice for Clinical Trials Unit, Inala
Peter Frith, MBBS, Principal Investigator, Affiliation: Flinders Medical Centre
Michael Crookes, MBBS, Principal Investigator, Affiliation: Peninsula Medical Centre
Alan James, MBBS, Principal Investigator, Affiliation: Sir Charles Gairdner Hospital
Phillip Thompson, MBBS, Principal Investigator, Affiliation: Mount Medical Centre

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.

Official title: A Phase II Study to Investigate Mannitol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease

Study design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Primary outcome: Forced expiratory volume in one second (FEV1)

Secondary outcome:

Response dose ratio (RDR)

Dose of provoking stimulus causing a 15%, 12% or 10% fall in FEV1 (PD15, PD12, PD10)

Lung function values

Quality of life assessed by St. George's Respiratory Questionnaire (SGRQ)- total score

COPD clinical control scores (CCQ)

Exacerbation frequency

Days on antibiotics

Days off work or days unable to carry out normal activities

Reversibility of airflow obstruction

Minimum age: 45 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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.

Respiratory Clinic, Sydney, New South Wales 2200, Australia

Peninsula Medical Centre, Umina, New South Wales 2257, Australia

Brisbane South Clinical Clinical Research Centre, Brisbane, Queensland 4152, Australia

Wesley Medical Centre, Auchenflower, Queensland 4066, Australia

Inala Health Centre, PO BOx 52, Inala, Queensland 4077, Australia

Respiratory Research Foundation Clinical Trial Centre, Toorak Gardens, South Australia 5056, Australia

Flinders University, Bedford Park, South Australia 5042, Australia

Peninsula Chest Clinic, Frankston, Victoria 3199, Australia

The rooms of Dr Chris Steinfort, Geelong, Victoria 3220, Australia

Rosebud Medical Centre, 1239- 1241 Point Nepean Rd, Rosebud, Victoria 3939, Australia

The Alfred Hospital, Melbourne, Victoria 3004, Australia

Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia

Mount Medical Centre, Perth, Western Australia 6005, Australia

Related publications:

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.

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.

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.

Koskela HO, Hyvarinen 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.

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.

Starting date: July 2005
Ending date: August 2006
Last updated: September 17, 2006