Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial

Chronic Obstructive Pulmonary Disease Clinical Trial

— ICE-T  

Official title:

Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03050424
• Other study ID #: 2016LF003B
• Secondary ID: 2016-000829-3916
• Status: Recruiting
• Phase: Phase 2
• First received: February 7, 2017
• Last updated: May 11, 2017
• Start date: April 1, 2017
• Est. completion date: January 1, 2019

Study information

• Verified date: May 2017
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: Matthew Pavitt, MBBS, MRCP
• Phone: 0207 351 8029
• Email: M.Pavitt[@]rbht.nhs.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 1, 2019
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. 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

2. Non-anaemic: males haemoglobin (Hb) = 130g/L, and females = 120g/L

3. Iron deficiency, defined as:

1. Serum Ferritin < 100 µg/ml

2. Serum Ferritin 100-299 µg/ml with Transferrin saturation (TSAT) < 16%

3. Soluble transferring receptor > 28.1nmol/L

4. No history of lower respiratory tract infection or exacerbation of COPD in the last 6 weeks

5. No participation in Pulmonary Rehabilitation (PR) for at least 3 months prior to initial assessment.

Exclusion Criteria:

1. Polycythemia defined as Hb > 170g/L and haematocrit > 0.6 in males and Hb > 150g/L and haematocrit > 0.56 in females.

2. Significant co-morbidity contributing to reduced exercise tolerance

3. Congestive cardiac failure defined as Left Ventricular Ejection Fraction (LVEF) < 45% or plasma B-type natriuretic peptide (BNP) > 100pg/ml.

4. Oral iron therapy at doses > 100mg/day in the previous week prior to randomisation.

5. Chronic liver disease (including active hepatitis) and/or screening alanine transaminase or aspartate transaminase above 3 times the upper limit of normal range.

6. Anaemia (WHO [31]) defined as Hb < 130g/L in males > 15 yrs old and Hb < 120g/L in non-pregnant females.

7. Current malignancy or haematological disorders.

8. Currently receiving systemic chemotherapy and/or radiotherapy.

9. Renal dialysis (previous, current or planned).

10. Unstable angina.

11. Subject is of child-bearing potential or is pregnant or breast feeding.

12. Contraindication to Ferrous Carboxymaltose (Ferinject):

1. Hypersensitivity to active substance

2. Known serious hypersensitivity to other parental iron substance

3. Anaemia not attributed to iron deficiency (e.g. other microcytic anaemia)

4. Evidence of iron overload or disturbance in utilisation of iron.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Ferric Carboxymaltose
Ferric Carboxymaltose injectable Product
• Sodium Chloride 0.9%
Sodium Chloride 0.9%

Locations

Country	Name	City	State
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

Demeyer H, Gimeno-Santos E, Rabinovich RA, Hornikx M, Louvaris Z, de Boer WI, Karlsson N, de Jong C, Van der Molen T, Vogiatzis I, Janssens W, Garcia-Aymerich J, Troosters T, Polkey MI; PROactive consortium.. Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used. PLoS One. 2016 Mar 14;11(3):e0151255. doi: 10.1371/journal.pone.0151255. eCollection 2016. — View Citation

Demeyer H, Louvaris Z, Frei A, Rabinovich RA, de Jong C, Gimeno-Santos E, Loeckx M, Buttery SC, Rubio N, Van der Molen T, Hopkinson NS, Vogiatzis I, Puhan MA, Garcia-Aymerich J, Polkey MI, Troosters T; Mr Papp PROactive study group and the PROactive consortium.. Physical activity is increased by a 12-week semiautomated telecoaching programme in patients with COPD: a multicentre randomised controlled trial. Thorax. 2017 May;72(5):415-423. doi: 10.1136/thoraxjnl-2016-209026. Epub 2017 Jan 30. — View Citation

Nolan CM, Maddocks M, Canavan JL, Jones SE, Delogu V, Kaliaraju D, Banya W, Kon SS, Polkey MI, Man WD. Pedometer Step Count Targets During Pulmonary Rehabilitation in COPD: A Randomized Controlled Trial. Am J Respir Crit Care Med. 2016 Dec 2. [Epub ahead of print] — View Citation

Zoumot Z, Davey C, Jordan S, McNulty WH, Carr DH, Hind MD, Polkey MI, Shah PL, Hopkinson NS. Endobronchial valves for patients with heterogeneous emphysema and without interlobar collateral ventilation: open label treatment following the BeLieVeR-HIFi study. Thorax. 2017 Mar;72(3):277-279. doi: 10.1136/thoraxjnl-2016-208865. Epub 2016 Dec 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Constant Rate Cycle Ergometry (75% Max Load)	Increased exercise capacity as assessed by endurance cycle ergometry at 75% VO2max	8 weeks
Secondary	Quality of Life	COPD Assessment Test (CAT)	Week 0; Week 8; Week 10; Week 14
Secondary	Quality of Life	Medical Research Council (MRC) Dyspnoea Scale	Week 0; Week 8; Week 10; Week 14
Secondary	Quality of Life	Hospital Anxiety and Depression (HAD) Scale	Week 0; Week 8; Week 10; Week 14
Secondary	Quality of Life	Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)	Week 0; Week 8; Week 10; Week 14
Secondary	Quality of Life	EuroQoL Group (EQ-5D-5L)	Week 0; Week 8; Week 10; Week 14
Secondary	Muscle Oxygen Delivery	Near infrared spectroscopy during muscle contraction	Week 0; Week 8; Week 14
Secondary	Endurance Shuttle Walk Test (ESWT)	Change in endurance shuttle walk test distance and time	Week 0; Week 4; Week 10; Week 14
Secondary	Adverse Effects of Iron Administration	Any adverse effects of intravenous iron administration	Week 0; Week 4; Week 8; Week 10; Week 14

External Links

•   Drug information for Ferinject (ferric carboxymaltose)
•   Drug information for Sodium Chloride Injection BP 0.9% w/v