31P MRS Ischaemic Exercise Optimisation and COPD

Atrophy, Muscular Clinical Trial

Official title:

31P MRS Ischaemic Exercise Optimisation and COPD Myopathy Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01476072
• Other study ID #: 113784
• Status: Completed
• Phase: Phase 1
• First received: September 29, 2011
• Last updated: June 27, 2013
• Start date: April 2010
• Est. completion date: August 2011

Study information

• Verified date: June 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

An MRI study to develop a reliable methodology for 31P MRS ischaemic exercise in order to obtain a consistent standard of measurement of muscle metabolism while maintaining an acceptable level of subject comfort and use optimised method to measure and compare metabolism in the biceps and quadriceps of patients with COPD-related myopathy and control subjects

Description:

31P Magnetic Resonance Spectroscopy (31P MRS) is a non-invasive method to measure muscle metabolism during exercise. This protocol is intended to provide information for planning future clinical trials applying 31P MRS as an endpoint measure for proof of pharmacology studies with novel therapeutic molecules. Parts A & B of this study will refine imaging and exercise protocols for 31P MRS during brief periods of muscle ischaemia and will assess the test-retest variance. In Part C we will apply 31P MRS with aerobic exercise in a pilot study to estimate differences in skeletal muscle oxidative metabolism between age- and sex-matched control subjects and patients with myopathy associated with Chronic Obstructive Pulmonary Disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Fit to safely tolerate procedures

2. Male or female between 18 and 80 years of age

3. If pre-menopausal female, non-pregnant on dipstick urinalysis

4. Subject and responsible physician agree that the subject will be able to comfortably lie in scanning position in the scanner for up to 90 minutes

5. Capable of giving written informed consent

6. All four limbs are intact and free of disease

The following criteria apply to patients with COPD myopathy only:

1. Established diagnosis of COPD with a disease classification of GOLD Stage II and above with suspected or established diagnosis of myopathy and/or COPD with low BMI (under 20 for men and under 19 for women) and/or MVC under 120% of the BMI.

2. At least a 20 pack year history of smoking

3. Resting oxygen saturation above 85% on room air

4. Ambulant and not oxygen-dependent at rest or during mild exertion

Exclusion Criteria:

1. Ineligible for MRI/MRS scanning in accordance to local MR safety regulations

2. Any medical condition, acute or chronic, that will lead to potential discomfort when lying supine in the magnet for periods up to 90 min

3. Any medical condition that will lead to potential discomfort with repetitive movement of the limb being tested in the scanner

4. Subjects undergoing ischaemic/anaerobic 31P MRS must have no history of clinically significant peripheral vascular disease, abnormal blood clotting, deep vein thrombosis or pulmonary embolism or suspected clinically significant signs of limb vascular disease on screening examination.

5. Subjects undergoing ischaemic/anaerobic 31P MRS must not have taken the oral contraceptive pill, hormone replacement therapy, or undergone anaesthesia within past 1 month, or have a history of recent prolonged immobility greater than 4 hours (e.g. air travel), or considered unfit in the opinion of the study physician

6. Concurrent medical conditions known or suspected that in the opinion of the responsible physician could confound interpretation of results.

7. A medical or psychiatric history that in the opinion of the responsible physician would risk safety of the subject or well-being of the subject.

The following criteria apply to control subjects and COPD patients participating in Part C of the study:

1. Oxygen saturations below 85% on room air at rest, or significant desaturation on mild exertion.

2. Current or recent (<4 weeks) infectious exacerbation of COPD requiring corticosteroid therapy at the time of screening or scanning visit day.

3. Any significant medical illness other than COPD which, in the opinion of the study physician, may preclude participation or which by virtue of being associated with muscle weakness may cause distortion of the results (e.g. neuromuscular disease, severe heart failure &c).

4. Control subjects with any history of regular smoking

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Atrophy, Muscular
• Muscular Atrophy

Intervention

Other:
• MRI scan
MRI scan only, methodology study with no other intervention

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	London

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	level of skeletal muscle metabolism	ADP, ATP, PCr, Pi, and pH will be measured during rest, anaerobic exercise and recovery to determine muscle metabolism.	1 year	No
Secondary	determine Markers of disease in patients with COPD-related myopathy	tests such as spirometry, muscle biopsy, muscle cross-sectional area CSA, muscle strength to indicate level of disease progression	1 year	No