Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial

Study Overview
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Brief Summary
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This phase II single centre, double blind, placebo-controlled, randomised trial aims to test the hypothesis that intravenous iron improves exercise performance in Chronic Obstructive Pulmonary Disease (COPD) as measured by constant rate cycle ergometry.

Detailed Description
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Iron deficiency (ID) is one of the most common nutritional deficiencies affecting humans. Chronic diseases, including COPD, are commonly complicated by iron deficiency anaemia (IDA). It has been well documented that there is an association between both ID and anaemia and reduced exercise capacity. It has been postulated that addressing this ID may be a novel approach to improve exercise capacity and quality of life. The ECLIPSE cohort found that the prevalence of anaemia in patients with COPD is 19% and is associated with functional limitation and poor outcomes; similarly Nickol et al (2015) found ID to be prevalent in 17.7% of patients with COPD. Barberan-Garcia et al (2015) evaluated the relationship between Non-anaemic iron deficiency (NAID) and aerobic capacity in seventy COPD patients before and after an 8 week high intensity endurance exercise training programme. Endurance time was assessed as endurance time during constant work rate exercise testing at 80% of oxygen consumption (VO2) peak. At baseline it was noted that the NAID group in comparison to the normal iron status group had a lower exercise tolerance of approximately 90 seconds, which is close to normally reported minimal clinical important difference (MCID's) for this test, P=0.007. After adjusting for confounding variables with a multiple regression analysis it was shown that training induced increase in aerobic exercise capacity was only found in the normal iron status group, with the effect of training on exercise tolerance being lower in the NAID (P=0.041). Exercise capacity in COPD is strongly linked to outcome measures and mortality. The benefit of correcting NAID in COPD subjects would be to achieve an increase in exercise endurance and thus an improvement in Quality of Life (QoL). Currently there is no standard treatment for NAID in COPD, so this pilot, randomised, double-blind, placebo-controlled trial will attempt to answer this question.

Official Title
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Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Ferric Carboxymaltose
* Drug: Sodium Chloride 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically stable patients (>18 years old), Global Initiative for Chronic Obstructive Lung Disease (GOLD) II-IV COPD Forced Expiratory Volume in 1 second (FEV1):Forced Vital capacity (FVC) < 0.70 Non-anaemic: males haemoglobin (Hb) ≥ 130g/L, and females ≥ 120g/L Iron deficiency, defined as: Serum Ferritin < 100 µg/ml Serum Ferritin 100-299 µg/ml with Transferrin saturation (TSAT) < 16% Soluble transferring receptor > 28.1nmol/L No history of lower respiratory tract infection or exacerbation of COPD in the last 6 weeks No participation in Pulmonary Rehabilitation (PR) for at least 3 months prior to initial assessment. Exclusion Criteria: Polycythemia defined as Hb > 170g/L and haematocrit > 0.6 in males and Hb > 150g/L and haematocrit > 0.56 in females. Significant co-morbidity contributing to reduced exercise tolerance Congestive cardiac failure defined as Left Ventricular Ejection Fraction (LVEF) < 45% or plasma B-type natriuretic peptide (BNP) > 100pg/ml. Oral iron therapy at doses > 100mg/day in the previous week prior to randomisation. Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of normal range. Anaemia (WHO [31]) defined as Hb < 130g/L in males > 15 yrs old and Hb < 120g/L in non-pregnant females. Current malignancy or haematological disorders. Currently receiving systemic chemotherapy and/or radiotherapy. Renal dialysis (previous, current or planned). Unstable angina. Subject is of child-bearing potential or is pregnant or breast feeding. Contraindication to Ferrous Carboxymaltose (Ferinject): Hypersensitivity to active substance Known serious hypersensitivity to other parental iron substance Anaemia not attributed to iron deficiency (e.g. other microcytic anaemia) Evidence of iron overload or disturbance in utilisation of iron.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Ferric Carboxymaltose (FCM) (Ferinject) at 15 mg iron/kg body weight | Drug: Ferric Carboxymaltose<br>* Ferric Carboxymaltose injectable Product<br>* Other names: Ferinject®;|
| Placebo Comparator: Placebo<br>Sodium Chloride 0.9% | Drug: Sodium Chloride 0.9%<br>* Sodium Chloride 0.9%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Constant Rate Cycle Ergometry (75% Max Load) | Increased exercise capacity as assessed by endurance cycle ergometry at 75% VO2max | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | COPD Assessment Test (CAT) | Week 0; Week 8; Week 10; Week 14 | 
| Quality of Life | Medical Research Council (MRC) Dyspnoea Scale | Week 0; Week 8; Week 10; Week 14 | 
| Quality of Life | Hospital Anxiety and Depression (HAD) Scale | Week 0; Week 8; Week 10; Week 14 | 
| Quality of Life | Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) | Week 0; Week 8; Week 10; Week 14 | 
| Quality of Life | EuroQoL Group (EQ-5D-5L) | Week 0; Week 8; Week 10; Week 14 | 
| Muscle Oxygen Delivery | Near infrared spectroscopy during muscle contraction | Week 0; Week 8; Week 14 | 
| Endurance Shuttle Walk Test (ESWT) | Change in endurance shuttle walk test distance and time | Week 0; Week 4; Week 10; Week 14 | 
| Adverse Effects of Iron Administration | Any adverse effects of intravenous iron administration | Week 0; Week 4; Week 8; Week 10; Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Iron, Exercise Capacity, Non-anaemic iron deficiency