Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial (ICE-T)

• ClinicalTrials.gov Identifier: NCT03050424
• Recruitment Status: Unknown
• First Posted: February 10, 2017
• Last Update Posted: May 12, 2017
• Sponsor: Royal Brompton & Harefield NHS Foundation Trust
• Information provided by (Responsible Party): Royal Brompton & Harefield NHS Foundation Trust

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Ferric Carboxymaltose; Drug: Sodium Chloride 0.9%	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind, placebo-controlled, randomised trial
• Primary Purpose: Treatment
• Official Title: Iron and Chronic Obstructive Pulmonary Disease (COPD) Exercise Trial
• Actual Study Start Date: April 1, 2017
• Estimated Primary Completion Date: October 1, 2018
• Estimated Study Completion Date: January 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active; Ferric Carboxymaltose (FCM) (Ferinject) at 15 mg iron/kg body weight	Drug: Ferric Carboxymaltose; Ferric Carboxymaltose injectable Product; Other Name: Ferinject®
Placebo Comparator: Placebo; Sodium Chloride 0.9%	Drug: Sodium Chloride 0.9%; Sodium Chloride 0.9%

Outcome Measures

Primary Outcome Measures :

1. Constant Rate Cycle Ergometry (75% Max Load) [ Time Frame: 8 weeks ]
   Increased exercise capacity as assessed by endurance cycle ergometry at 75% VO2max

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Matthew Pavitt, MBBS, MRCP; 0207 351 8029; M.Pavitt@rbht.nhs.uk

Locations

United Kingdom

Royal Brompton & Harefield NHS Foundation Trust; Recruiting

London, United Kingdom, SW3 6HP

Contact: Matthew Pavitt, MBBS, MRCP

Sponsors and Collaborators

Royal Brompton & Harefield NHS Foundation Trust

Investigators

• Principal Investigator: Michael Polkey, MRCP, PhD; Royal Bromtpon and Harefield NHS Foundation Trust

More Information

Additional Information:

Drug information for Sodium Chloride Injection BP 0.9% w/v 

Drug information for Ferinject (ferric carboxymaltose) 

Publications:

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.

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.

Nolan CM, Maddocks M, Canavan JL, Jones SE, Delogu V, Kaliaraju D, Banya W, Kon SSC, Polkey MI, Man WD. Pedometer Step Count Targets during Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial. Am J Respir Crit Care Med. 2017 May 15;195(10):1344-1352. doi: 10.1164/rccm.201607-1372OC.

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.

• Responsible Party: Royal Brompton & Harefield NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT03050424
• Other Study ID Numbers: 2016LF003B; 2016-000829-39 ( EudraCT Number ); 16/EE/0355 ( Other Identifier: REC Reference )
• First Posted: February 10, 2017
• Last Update Posted: May 12, 2017
• Last Verified: May 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Royal Brompton & Harefield NHS Foundation Trust:

COPD; Iron; Exercise Capacity; Non-anaemic iron deficiency

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases