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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Diseases, Obstructive
• Intervention / Treatment: Drug: Dry powder mannitol; Drug: Budesonide 400mcg administered via turbuhaler; Drug: Ipratropium bromide 80mcg; Drug: Salbutamol 400mcg

• Study Type: Interventional
• Enrollment: 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2200
      • Respiratory Clinic
    • Umina, New South Wales, Australia, 2257
      • Peninsula Medical Centre
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Wesley Medical Centre
    • Brisbane, Queensland, Australia, 4152
      • Brisbane South Clinical Clinical Research Centre
    • PO BOx 52, Inala, Queensland, Australia, 4077
      • Inala Health Centre
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders University
    • Toorak Gardens, South Australia, Australia, 5056
      • Respiratory Research Foundation Clinical Trial Centre
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Chest Clinic
    • Geelong, Victoria, Australia, 3220
      • The rooms of Dr Chris Steinfort
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Rosebud, Victoria, Australia, 3939
      • Rosebud Medical Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
    • Perth, Western Australia, Australia, 6005
      • Mount Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 43 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Forced expiratory volume in one second (FEV1)

Secondary Outcome Measures

Outcome Measure
Days on antibiotics
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 off work or days unable to carry out normal activities
Reversibility of airflow obstruction

Collaborators and Investigators

• Sponsor: Pharmaxis
• Investigators: Principal Investigator: Alvin Ing, MBBS, Bankstown Hospital; Principal Investigator: Martin Coffey, MBBS, Rosebud Medical Centre; Principal Investigator: David Langton, MBBS, Peninsula Chest Clinic, Frankston; Principal Investigator: Chris Steinfort, MBBS, The Rooms of Dr Steinfort, Geelong; Principal Investigator: Trevor WIlliams, MBBS, The Alfred; Principal Investigator: Peter Frith, MBBS, Flinders Medical Centre; Principal Investigator: Michael Chia, MBBS, Respiratory Research Foundation, Toorak Gardens; Principal Investigator: Maureen McKeirnan, MBBS, Brisbane South Medical Centre; Principal Investigator: Fred de Looze, MBBS, Centre for General Practice for Clinical Trials Unit, Inala; Principal Investigator: Michael Crookes, MBBS, Peninsula Medical Centre; Principal Investigator: Alan James, MBBS, Sir Charles Gairdner Hospital; Principal Investigator: Phillip Thompson, MBBS, Mount Medical Centre

Publications and helpful links

General 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. doi: 10.1164/ajrccm.156.3.9701113.
• 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. doi: 10.1378/chest.124.4.1341.
• 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. doi: 10.1046/j.1440-1843.2002.00357.x.
• 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. doi: 10.1136/thorax.58.8.654.
• 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. doi: 10.1016/j.pupt.2004.10.005. Epub 2004 Dec 21.

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Study Completion: August 1, 2006

Study Registration Dates

• First Submitted: June 30, 2005
• First Submitted That Met QC Criteria: July 1, 2005
• First Posted (Estimate): July 4, 2005

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 18, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Mannitol; Budesonide; Albuterol; Bromides; Ipratropium
• Other Study ID Numbers: DPM-COPD-201