Clinical trial NCT00117182: Aridol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in COPD
Official title: A Phase II Study to Investigate Mannitol Challenge as a Tool to Predict Treatment Response to Inhaled Corticosteroids in COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Diseases, Obstructive
Lead sponsor: Syntara
Sponsor class: INDUSTRY
First posted: 2005-07-04
Enrollment: 140
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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.


Eligibility 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.

Primary outcomes:
measure: Forced expiratory volume in one second (FEV1)
Secondary outcomes:
measure: Response dose ratio (RDR)
measure: Dose of provoking stimulus causing a 15%, 12% or 10% fall in FEV1 (PD15, PD12, PD10)
measure: Lung function values
measure: Quality of life assessed by St. George's Respiratory Questionnaire (SGRQ)- total score
measure: COPD clinical control scores (CCQ)
measure: Exacerbation frequency
measure: Days on antibiotics
measure: Days off work or days unable to carry out normal activities
measure: Reversibility of airflow obstruction
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Respiratory Clinic
state: New South Wales
city: Umina
country: Australia
facility: Peninsula Medical Centre
state: New South Wales
city: Auchenflower
country: Australia
facility: Wesley Medical Centre
state: Queensland
city: Brisbane
country: Australia
facility: Brisbane South Clinical Clinical Research Centre
state: Queensland
city: PO BOx 52, Inala
country: Australia
facility: Inala Health Centre
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders University
state: South Australia
city: Toorak Gardens
country: Australia
facility: Respiratory Research Foundation Clinical Trial Centre
state: South Australia
city: Frankston
country: Australia
facility: Peninsula Chest Clinic
state: Victoria
city: Geelong
country: Australia
facility: The rooms of Dr Chris Steinfort
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Rosebud
country: Australia
facility: Rosebud Medical Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Mount Medical Centre
state: Western Australia
Study officials:
affiliation: Bankstown Hospital
name: Alvin Ing, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Rosebud Medical Centre
name: Martin Coffey, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Peninsula Chest Clinic, Frankston
name: David Langton, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: The Rooms of Dr Steinfort, Geelong
name: Chris Steinfort, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred
name: Trevor WIlliams, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Flinders Medical Centre
name: Peter Frith, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Respiratory Research Foundation, Toorak Gardens
name: Michael Chia, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Brisbane South Medical Centre
name: Maureen McKeirnan, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for General Practice for Clinical Trials Unit, Inala
name: Fred de Looze, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Peninsula Medical Centre
name: Michael Crookes, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Sir Charles Gairdner Hospital
name: Alan James, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Medical Centre
name: Phillip Thompson, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1046/j.1440-1843.2002.00357.x.
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. doi: 10.1136/thorax.58.8.654.
citation: 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.
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. doi: 10.1016/j.pupt.2004.10.005. Epub 2004 Dec 21.