Impact of Intravenous Iron on Musculoskeletal Function in Older Adults (FERIDA)

Impact of Intravenous Iron (Ferinject) on Musculoskeletal Function Profiles in Older Adults With Iron Deficiency Anaemia (IDA)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Iron Deficiency Anemia
• Intervention / Treatment: Drug: Ferinject; Drug: Ferrous Sulfate 200 MG

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Professor Khaiyat; Phone Number: 00441512913262; Email: alizado@hope.ac.uk
• Study Contact Backup: Name: Mrs Smylie; Phone Number: 00441512913996; Email: smylieg@hope.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Anaemia attributable to iron deficiency
• Haemoglobin < 120 g/L in women, Hb < 130 g/L in men
• Ferritin ≤100 ng/mL or ≤300 ng/mL if transferrin saturation (TSAT) ≤30%
• Age ≥ 60 to 85 years
• Ambulatory individuals
• Written informed consent

Exclusion Criteria:

• Patients already taking intravenous or oral iron
• BMI > 40 kg/m²
• Uncontrolled hypertension/ diabetes
• Potential medication interactions
• Hemochromatosis or iron storage disorders
• Recent treatment with IV antibiotics or red blood cell transfusion
• Dialysis dependent
• History of malignancy
• Pregnant or lactating women
• Severe hepatic and renal dysfunction
• Advanced cardiovascular disease and COPD
• Advanced Neuromuscular disorder
• Obvious cognitive disability and psychological illness
• Current treatment with systemic steroids or any other substantive medication
• Alcohol or any other drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Ferinject; Ferinject Therapy Group: each patient's Iron need for repletion by the Ferinject will be determined using product SPC dosing based on patient's body weight and Hb level. Accordingly, the appropriate dose of Ferinject will be administered while ensuring that a single administration will not exceed: 15 mg iron/kg body weight (for administration by intravenous injection) or 20 mg iron/kg body weight (for administration by intravenous infusion); 1,000 mg of iron (20 mL Ferinject) The cumulative dose of Ferinject per week will not exceed 1,000 mg of iron (20 mL Ferinject).; Other Names: ferric carboxymaltose
ACTIVE_COMPARATOR: Active Control Group; This group will receive oral ferrous sulphate prescribed by their GP Randmisation: Simple randomisation/parallel assignment/single-blinded	Drug: Ferrous Sulfate 200 MG; Active Control Group (standard care excl. IV Iron): Oral Ferrous sulphate 200 mg three times daily.; Other Names: oral iron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle Quality Index (MQI)	Muscle strength relative to volume of the muscle mass generating the force	"through study completion, an average of 2 year"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-history Questionnaire	Questionnaire to document participant health history	Baseline
International Physical Activity Questionnaire-IPAQ)	Questionnaire to determine the level of physical activity	Baseline
Blood Iron Profile	Blood analysis including Hemoglobin, Iron, Ferritin, and Transferrin	"Through study completion, an average of 2 year"
Upper Extremity Strength (in Newtons)	Dynamometry to measure upper extremity (Grip and shoulder forward flexion) strength	"Through study completion, an average of 2 year"
Lower Extremity Muscle Strength (in Newtons)	Dynamometry to measure lower extremity (Knee extension) strength	"Through study completion, an average of 2 year"
Skeletal Muscle Mass (kg)	Bio-Impedance (BIA) to measure the skeletal muscle mass (kg)	"Through study completion, an average of 2 year"
Muscle Fatigue	Electromyographic (EMG) assessment of localised muscle fatigue	"Through study completion, an average of 2 year"
Muscle Activation	Electromyographic (EMG) assessment of muscle activity level	"through study completion, an average of 2 year"
Gait Analysis	3-Dimensional Motion Capture to assess gait quality	"Through study completion, an average of 2 year"
Short Battery of Physical Performance (SBPP)	A validated test for assessing physcial and functional capacity	"through study completion, an average of 2 year"
Mitochondrial Function	Near-infrared spectroscopy (NIRS) to investigate quality of oxidation in muscles	"through study completion, an average of 2 year"
The 12-Item Short Form Health Survey (SF-12)	A patient-rated questionnaire to assess the Quality of Life	"Through study completion, an average of 2 year"
The Hospital Anxiety and Depression Scale (HADS)	A patient-rated questionnaire to assess anxiety and Depression	"Through study completion, an average of 2 year"
The Sarcopenia Quality of Life (SarQoL)	A patient-rated questionnaire to assess Sarcopenia-specific quality of life	"through study completion, an average of 2 year"
The Upper Extremity Functional Index (UEFI)	A patient-rated questionnaire to assess Upper Extremity Function	"through study completion, an average of 2 year"
The Lower Extremity Functional Index (UEFI)	A patient-rated questionnaire to assess Lower Extremity Function	"through study completion, an average of 2 year"

Collaborators and Investigators

• Sponsor: Liverpool Hope University
• Collaborators: Liverpool University Hospitals NHS Foundation Trust

Publications and helpful links

Helpful Links

• ISRCTN
• NHS/HRA
• WHO - International Trial Registry Platform

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2023
• Primary Completion (ANTICIPATED): August 1, 2026
• Study Completion (ANTICIPATED): January 1, 2027

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (ACTUAL): February 1, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2023
• Last Update Submitted That Met QC Criteria: January 23, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Ageing; Musculoskeletal; Skeletal Muscle Function; Iron Deficiency Anaemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases
• Other Study ID Numbers: LHU-FERIDA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: NK

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No