Last updated: 11/03/2018 11:27:38
Helium-3 MRI Imaging Study in COPD
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A randomized, methodology study to investigate the use of 3He-MRI lung ventilation and proton MRI perfusion imaging to detect changes in ventilation perfusion relationships in Chronic Obstructive Pulmonary Disease (COPD) patients; a proof of concept study.
Trial description: This protocol describes the investigation of the use of hyperpolarised helium magnetic resonance imaging (MRI) in reflecting the regional differences in lung function of moderate to severe Chronic Obstructive Pulmonary Disease (COPD) patients. Since finalisation of the original protocol, new medications for COPD have received Market Authorisation Approvals. Protocol Amendment 02 has been prepared to include these medications in the protocol eligibility criteria and restrictions for the study.
Primary purpose:
Diagnostic
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Changes in Oxygen Saturation
Timeframe: Baseline measurement at screening visit (up to 30 days prior to first dose). Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post dose), for both treatment periods.
Changes in distribution of regional ventilation/perfusion assessed by spatially registered Helium-3 Magnetic Resonance Imaging (MRI) and proton perfusion MRI.
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.
Secondary outcomes:
Changes in lung volumes.
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.
Changes in standard lung function parameters.
Timeframe: Baseline measurement at screening visit (up to 30 days prior to first dose). Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post dose), for both treatment periods.
Number of adverse events
Timeframe: From screening (up to 30 days prior to Day 1) to follow-up (7-14 days after last dose).
Reproducibility of Helium-3 MRI
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) for both treatment periods.
Symptomatic effects of bronchodilators.
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.
Regional lung oxygen uptake (pO2)
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.
Change in breathlessness
Timeframe: From screening (up to 30 days prior to Day 1) to follow-up (7-14 days after last dose).
Helium-3 apparent diffusion coefficient measurements
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.
Distribution of flow velocities in major airways
Timeframe: Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.
Changes in dyspnoea
Timeframe: From screening (up to 30 days prior to first dose) to follow-up (7-14 days after last dose).
Interventions:
Enrollment:
11
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
ipratropium bromide, salbutamol
Collaborators
Not applicable
Study date(s)
August 2010 to July 2011
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
50+ years
Accepts healthy volunteers
No
- Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) diagnosis: an established clinical history of chronic pulmonary disorder in accordance with the following description by the American Thoracic Society / European Respiratory Society [ATS / ETS, 2004]
- Chronic obstructive pulmonary disease is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
- Unstable cardiac disease or history of clinically significant arrhythmia (including established atrial fibrillation).
- Patients with a primary diagnosis of α-1 antitrypsin deficiency.
Inclusion and exclusion criteria
Inclusion criteria:
- Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) diagnosis: an established clinical history of chronic pulmonary disorder in accordance with the following description by the American Thoracic Society / European Respiratory Society [ATS / ETS, 2004] Chronic obstructive pulmonary disease is a preventable and treatable disease characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
- The patient is clinically stable with no change in symptoms or medication, no admissions to hospital, and with neither antibiotic therapy nor systemic steroid use for at least 6 weeks prior to screening. (Screening may be rescheduled after an appropriate period of stability)
- Male and female patients aged ≥50 years
- A female patient is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) ≥40 M1U/mL and estradiol ≤ 40 pg/mL (≤140 pmol/L) is confirmatory).
- Subjects have refrained from short-acting bronchodilators for 8 hours, long-acting β2-agonists (including any long-acting β2 agonist containing inhaler) and theophyllines for 24 hours and Tiotropium, phosphodiesterase-4 (PDE4) inhibitors (e.g. Roflumilast) and ultra long-acting beta-adrenoceptor agonists (e.g. Indacaterol) for 48 hours prior to admission to the unit on study days.
- Subjects with a post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) < 0.7
- Subjects with a post-bronchodilator FEV1 ≥ 30% and ≤ 80% of predicted normal for height, age and sex at screening.
- Subjects with a cigarette smoking history of ≥10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or the equivalent). Both current and former smokers are eligible to be enrolled.
- Resting SpO2 of >90% on room air
- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block (based on a single ECG value).
- The patient is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions, and to give informed consent.
Exclusion criteria:
- Unstable cardiac disease or history of clinically significant arrhythmia (including established atrial fibrillation).
- Patients with a primary diagnosis of α-1 antitrypsin deficiency.
- Patients with other significant respiratory disorders.
- Patients with any acute infection, exacerbation of COPD or other unstable medical condition.
- Patients in whom inhaled beta-2 agonists or anticholinergics are contraindicated.
- Patients who have undergone thoracic surgery including lung volume reduction surgery or have conditions that prevent them from performing spirometry and other physiological testing.
- Patients who are non Magnetic Resonance Imaging (MRI) compatible (ferro-magnetic metallic implants, pacemakers) as per the MRI questionnaire.
- Patients with renal complaints relating to potential adverse reactions to Gd-DTPA intravascular MRI contrast agent.
- Patients who suffer from claustrophobia.
- The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first study day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) of that study.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Subjects must abstain from taking prescription (not related to their COPD) or nonprescription drugs (including vitamins and dietary or herbal supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first study day until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
- Unwillingness or inability to follow the procedures outlined in the protocol.
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2011-04-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 111175 can be found on the GSK Clinical Study Register.
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