Helium-3 MRI Imaging Study in COPD

NCT02207452 | Completed Phase 1

• 1 other identifier: 111175
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Hyperpolarised helium-3; Lung Imaging; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (2)

• Changes in Oxygen Saturation

  To correlate changes in oxygen saturation pre- and post- bronchodilator (as a reflection of ventilation/perfusion matching) with changes in distribution of regional ventilation/perfusion (V/Q) demonstrated by hyperpolarized helium ventilation MRI/spatially registered proton perfusion.

  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.

  To correlate changes in oxygen saturation pre- and post- bronchodilator (as a reflection of ventilation/perfusion matching) with changes in distribution of regional ventilation/perfusion (V/Q) demonstrated by hyperpolarized helium ventilation MRI/spatially registered proton perfusion.

  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 (10)

• Changes in lung volumes.

  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.

  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

  From screening (up to 30 days prior to Day 1) to follow-up (7-14 days after last dose).

• Reproducibility of Helium-3 MRI

  Pre-treatment Day 1 (0.5-2 hours pre-dose) for both treatment periods.

• Symptomatic effects of bronchodilators.

  Pre-treatment Day 1 (0.5-2 hours pre-dose) and post-dose Day 1 (1 hour post-dose), for both treatment periods.

Study Arms (2)

Salbutamol + Ipratropium

OTHER

Treatment period 1: Salbutamol 5mg nebulised, single Dose. Treatment period 2: Ipratropium 500mcg nebulised, single dose.

Device: He-3 MRI; Drug: Salbutamol; Drug: Ipratropium; Device: MRI

Ipratropium + Salbutamol

OTHER

Treatment period 1: Ipratropium 500mcg nebulised, single dose. Treatment period 2: Salbutamol 5mg nebulised, single Dose.

Device: He-3 MRI; Drug: Salbutamol; Drug: Ipratropium; Device: MRI

Interventions

He-3 MRI DEVICE

Hyperpolarised helium-3 Magnetic Resonance Imaging (MRI) scan pre-bronchodilator and 1 hour post-bronchodilator (after 1 hour post-bronchodilator assessments/procedures completed).

Also known as: Hyperpolarised Helium-3 MRI, He-3 Magnetic Resonance Imaging

Ipratropium + Salbutamol; Salbutamol + Ipratropium

Salbutamol DRUG

Salbutamol 5mg nebulised single dose

Ipratropium + Salbutamol; Salbutamol + Ipratropium

Ipratropium DRUG

Ipratropium 500mcg nebulised single dose

Ipratropium + Salbutamol; Salbutamol + Ipratropium

MRI DEVICE

Proton Magnetic Resonance Imaging (MRI) scan pre-bronchodilator and 1 hour post-bronchodilator (after 1 hour post-bronchodilator assessments/procedures completed).

Also known as: 1H MRI

Ipratropium + Salbutamol; Salbutamol + Ipratropium

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Sheffield, S10 2JF, United Kingdom

Location

Related Links

• Results for study 111175 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Albuterol; Ipratropium

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2012
• First Posted: August 4, 2014
• Study Start: August 5, 2010
• Primary Completion: July 4, 2011
• Study Completion: July 4, 2011
• Last Updated: June 27, 2017

Record last verified: 2017-06

Locations

GB (1)