Impact of intravenous iron injections on musculoskeletal function in older adults
| ISRCTN | ISRCTN13325706 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13325706 |
| EudraCT/CTIS number | 2020-000056-35 |
| IRAS number | 253852 |
| Secondary identifying numbers | CPMS 44977, IRAS 253852 |
- Submission date
- 25/01/2021
- Registration date
- 28/01/2021
- Last edited
- 04/03/2024
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Anaemia is caused by a lack of iron, often because of blood loss or pregnancy. Anaemia is a risk factor for functional decline and frailty in older adults including decreased physical performance and muscle strength, increased hospitalisation risk and mortality, falls, and poorer recovery from activities of daily living. Iron deficiency and associated anaemia is a frequent accompanier of debilitating chronic diseases such as heart failure and chronic lung diseases.
These conditions, more commonly seen in older patients, are strongly linked to deterioration in physical function, reduced skeletal muscle mass and quality, frailty, and poor quality of life. Exercise intolerance is also a common feature of these conditions as iron deficiency impairs the capacity of carrying oxygen leading to inability to sustain physical activities. Furthermore, the age-related decline in the muscle mass and quality (so-called sarcopenia) and associated frailty has rapidly become a major health concern in the older adults, particularly when accompanied by other chronic diseases. Recently, there has been an increasing interest in exploring the role of iron as a causative factor in the development of sarcopenia and related frailty.
In summary, it is not clear whether Iron repletion leads to meaningful enhancements in the skeletal muscle function and physical performance in older adults suffering from iron deficiency anaemia. This study will investigate the impact of a standard care intervention (intravenous iron therapy) on muscular function and physical performance in older patients through a range of laboratory assessments.
Who can participate?
Patients aged 60 - 85 years, who have iron deficiency anaemia.
What does the study involve?
Participants will be randomly allocated to receive either intravenous iron therapy or oral ferrous sulphate. Each participant will require to attend the School of Health Sciences' laboratories (Liverpool Hope University) on four different occasions (once before intervention and three times after receiving the iron therapy) throughout a 3-year period to complete multiple assessments in relation to basic blood tests and musculoskeletal function and physical performance. In addition to this, participants in the first group will require to attend the Aintree Hospital NHS Trust clinics on one occasion to receive a single-dose intravenous iron.
The study will broadly investigate musculoskeletal function (health) and physical performance by means of muscle quality, muscle mass, muscle strength, muscle activation and fatigue levels, gait quality, muscle physiology (level of oxygen carried into the muscles), and functional questionnaires prior to, during, and after iron therapy. In addition to this, changes in patients' quality of life in each group will be assessed through administration of validated questionnaires.
What are the possible benefits and risks of participating?
Benefits: We cannot promise that this study will help you directly but the information we get from this study might help improve the treatment of older people suffering from iron deficiency anaemia.
Risks: Generally intravenous iron is very safe and well tolerated. However, there are known side effects including nausea, headaches, dizziness, high blood pressure, injection site reactions, increased liver enzymes. and allergic reaction.
Where is the study run from?
Liverpool Hope University (UK)
When is the study starting and how long is it expected to run for?
April 2019 to October 2025
Who is funding the study?
Vifor Pharma UK Limited
Who is the main contact?
Prof. Omid Khaiyat, alizado@hope.ac.uk
Contact information
Scientific
Liverpool Hope University
School of Health Sciences
Hope Park
Liverpool
L16 9JD
United Kingdom
 ORCID ID |
0000-0002-0509-9172 |
|---|---|
| Phone | +44 (0)151 2913262 |
| alizado@hope.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Impact of intravenous iron (Ferinject) on musculoskeletal function profiles in older adults with Iron Deficiency Anaemia (IDA) |
| Study objectives | Anaemia is a risk factor for functional decline and frailty in older adults including decreased physical performance and muscle strength, increased hospitalisation risk and mortality, falls, and poorer recovery from activities of daily living. Despite a major gap in human studies, research in animals has demonstrated an interrelationship between iron deficiency anaemia and deteriorated functional capacity and physical performance particularly in older adults. Iron deficiency and associated anaemia is a frequent accompanier of debilitating chronic diseases such as heart failure and chronic lung diseases. These conditions, more commonly seen in older patients, are strongly linked to deterioration in physical function, reduced skeletal muscle mass and quality, frailty, and poor quality of life. Exercise intolerance is also a common feature of these conditions as iron deficiency impairs the capacity of carrying oxygen leading to inability to sustain physical activities. Furthermore, the age-related decline in the muscle mass and quality (so called sarcopenia) and associated frailty has rapidly become a major health concern in the older adults particularly when accompanied by other chronic diseases. Recently, there has been an increasing interest in exploring the role of iron as a causative factor in the development of sarcopenia and related frailty. In summary, there is a substantial gap of evidence whether Iron repletion leads to meaningful enhancements in the skeletal muscle function and physical performance in older adults suffering from iron deficiency anaemia. This study will investigate the impact of a standard care intervention (intravenous iron therapy) on muscular function and physical performance in older patients through a range of laboratory assessments. |
| Ethics approval(s) | Approved 16/09/2020, North West - Liverpool Central Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44(0)207 1048387; liverpoolcentral.rec@hra.nhs.uk), ref: 20/NW/0090 |
| Health condition(s) or problem(s) studied | Iron deficiency anaemia |
| Intervention | The study will recruit two groups of stable patients (although likely with chronic diseases) with established iron deficiency anaemia through Aintree Hospital NHS Trust clinics. Fifty patients aged 60-85 years will be recruited into each group: 1. Intravenous iron therapy group: This group will receive intravenous iron calculated based on body weight and level of anaemia (hemoglobin concentration), as per the iron therapy's SPC 2. Active Control Group: This group will receive oral ferrous sulphate prescribed by their GP Randmisation: Simple randomisation/parallel assignment/single-blinded Identified patients with iron deficiency anaemia will receive an invitation to participate in the study together with a Patient Information Sheet clearly explaining different aspects of the research project. Each participant will require to attend the School of Health Sciences' laboratories (Liverpool Hope University) on four different occasions (once before the intervention and three times after receiving the iron therapy) throughout a 3-year period to complete multiple assessments in relation to basic blood tests and musculoskeletal function and physical performance. In addition to this, participants in the first group will require to attend the Aintree Hospital NHS Trust clinics on one occasion to receive a single-dose intravenous iron. The study will broadly investigate musculoskeletal function (health) and physical performance by means of muscle quality, muscle mass, muscle strength, muscle activation and fatigue levels, gait quality, muscle physiology (level of oxygen carried into the muscles), and functional questionnaires prior to, during, and after iron therapy. In addition to this, changes in patients' quality of life in each group will be assessed through administration of validated questionnaires. The data will be analysed at the end of the study to identify any significant and clinically meaningful changes in the musculoskeletal function, physical performance, and health-related quality of life resulted from the iron therapy in each group while also comparing such changes between the two study groups. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Ferinject (ferric carboxymaltose), ferrous sulphate (oral) |
| Primary outcome measure | Muscle Quality Index (MQI) determined based on muscle strength relative to quantity/volume of the muscle mass generating the force. Muscle strength will be measured using various dynamometers designed for upper and lower extremities and muscle volume will be assessed using the Bioimpedance technique at screening, week 4, week 12 and week 24 |
| Secondary outcome measures | 1. History & Health Screening measured at screening: 1.1. Health-history measured using the Health-history Questionnaire 1.2. Resting Heart Rate 1.3. Blood Pressure (mmHg) 1.4. Height (cm), weight (kg), BMI (kg/m²), Waist Circumference (cm) 1.5. Physical activity measured using the International Physical Activity Questionnaire 2. Biochemical parameters: Blood count, Serum Iron, Serum Ferritin and Transferrin levels measured using blood test at screening, week 4, week 12 and week 24 3. Muscular Function Profile including strength Measurements of the key muscle groups essential for daily activities and independence including hand-grip, shoulder, knee at screening, week 4, week 12 and week 24 4. Skeletal Muscle Mass measured using Segmental Bio-Impedance at screening, week 4, week 12 and week 24 5. Fatigability and Activation Pattern of key lower & upper extremity muscle groups measured using electromyography and gait analysis at screening, week 4, week 12 and week 24 6. Mitochondrial Function measured using near-infrared spectroscopy atscreening, week 4, week 12 and week 24 7. Health-related Quality of Life: SF-12 Health Survey, The single-item ‘Life Satisfaction and Personal Well-Being’ question at screening, week 4, week 12 and week 24 8. Anxiety and depression measured using the Hospital Anxiety and Depression Scale at screening, week 4, week 12 and week 24 9. Mood measured using the Profile of Mood States – Short Form at screening, week 4, week 12 and week 24 |
| Overall study start date | 01/04/2019 |
| Completion date | 01/06/2026 |
| Reason abandoned (if study stopped) | Lack of funding/sponsorship |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 60 Years |
| Upper age limit | 85 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 100; UK Sample Size: 100 |
| Key inclusion criteria | 1. Anaemia attributable to iron deficiency 2. Haemoglobin <120 g/L in women, Hb <130 g/L in men 3. Ferritin <=100 ng/mL or <=300 ng/mL if transferrin saturation (TSAT) <=30% 4. Age >=60 to 85 years 5. Ambulatory individuals 6. BMI <=40 kg/m² 7. Written informed consent |
| Key exclusion criteria | 1. Uncontrolled hypertension/ diabetes 2. Potential medication interactions 3. Hemochromatosis or iron storage disorders 4. Recent treatment with IV antibiotics or red blood cell transfusion 5. Dialysis dependent 6. History of malignancy 7. Pregnant or lactating women 8. Severe hepatic and renal dysfunction 9. Advanced cardiovascular disease and COPD 10. Advanced Neuromuscular disorder 11. Obvious cognitive disability and psychological illness 12. Current treatment with systemic steroids or any other substantive medication 13. Alcohol or any other drug abuse |
| Date of first enrolment | 20/02/2023 |
| Date of final enrolment | 30/12/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Hope Park
Liverpool
L16 9JD
United Kingdom
Lower Lane
Liverpool
L9 7AL
United Kingdom
Sponsor information
University/education
Hope Park
Liverpool
L16 9JD
England
United Kingdom
| Phone | +44 (0)151 291 3745 |
|---|---|
| cooperc1@hope.ac.uk | |
| Website | http://www.hope.ac.uk/ |
"ROR" |
https://ror.org/03ctjbj91 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 01/09/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
04/03/2024: This study has been withdrawn without any recruitment. The project was externally funded, unfortunately the external funder terminated the agreement due to a change in its management.
17/01/2023: The recruitment start date was changed from 01/01/2023 to 20/02/2023.
18/10/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/10/2022 to 01/01/2023.
2. The recruitment end date has been changed from 01/10/2024 to 30/12/2025.
3. The overall trial end date has been changed from 01/10/2025 to 01/06/2026 and the plain English summary has been updated to reflect this change.
25/04/2022: The following changes have been made:
1. The recruitment start date has been changed from 01/10/2021 to 01/10/2022.
2. The recruitment end date has been changed from 01/04/2022 to 01/10/2024.
3. The overall trial end date has been changed from 01/04/2023 to 01/10/2025 and the plain English summary has been updated to reflect this change.
4. The intention to publish date has been changed from 01/09/2024 to 01/09/2026.
18/10/2021: The recruitment start date has been changed from 01/10/2021 to 01/01/2022.
19/04/2021: The recruitment start date was changed from 01/04/2021 to 01/10/2021.
25/01/2021: Trial’s existence confirmed by National Institute for Health Research (NIHR)
