Ferric Carboxymaltose to Improve Skeletal Muscle Metabolism in Heart Failure Patients With Functional Iron Deficiency
Condition: Iron-deficiency
MeSH terms: Heart Failure; Anemia, Iron-Deficiency; Iron Deficiencies
Intervention: Ferric Carboxymaltose; Placebo; 31P MRS/MRI
Intervention description: Intravenous Ferric Carboxymaltose 750 mg mixed under sterile conditions in 100 ml of normal saline for final concentration of 7.5 mg/ml and administered via volumetric infusion pump over 15 minutes.; 100 ml of normal saline solution, and administered via volumetric infusion pump over 15 minutes.; Each participant will perform the same rhythmic plantar extension exercise protocol twice, for sequential acquisition of magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) measurements. For the exercise protocol, the participant will lay supine on the scanning table with the right leg inside the volume coil. The exercise consists of repeated plantar flexion movements using resistance bands at a frequency of one repetition per second for 1-2 minutes. Data are collected continuously for 2 minutes before the exercise (baseline), during exercise, and 5 minutes after the exercise for the MRS and MRI experiments.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 20.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Injectafer; ferric carboxymaltose; Supplemental Iron

Summary:

      The purpose of this study is to better understand how body levels of iron affect the ability
      to exercise in patients with heart failure (HF).

      Heart failure is a condition in which abnormal pumping action of the heart reduces the flow
      of blood to the body. Patients with heart failure may feel shortness of breath or leg fatigue
      when they exercise. Iron is an essential nutrient in the diet. In heart failure patients, low
      body levels of iron might increase shortness of breath and fatigue.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Symptomatic NYHA Class II-III heart failure >3 months

          -  Guideline-recommended heart failure treatment for > 3 months

          -  Hemoglobin >13 g/dl for men and >12 g/dl for women

          -  Functional iron deficiency (defined as serum ferritin level <100 ng/ml or between 100
             and 299 ng/ml with transferrin saturation <20%)

          -  Left ventricular ejection fraction <40%, or left ventricular ejection fraction ≥40%
             with left atrial enlargement (left atrial volume index >28 ml/m2) and/or left
             ventricular hypertrophy (left ventricular mass index >95 g/m2 (women) or >115 g/m2
             (men) determined by echocardiogram within last 24 months.

          -  Able and willing to provide written informed consent

        Exclusion Criteria:

          -  Presence of implantable defibrillator, permanent pacemaker, other metal implant not
             compatible with 3TMRS/MRI, or other contraindication to 3T MRS/MRI procedures

          -  Heart failure due to infiltrative cardiomyopathy, restrictive cardiomyopathy, or
             hypertrophic cardiomyopathy

          -  Weight <50 kg or >120 kg

          -  Coronary or cerebral atherothrombotic events in the past 6 months

          -  Hospitalization of emergency room visit for heart failure within past 3 months

          -  ICD shock in last 3 months

          -  Known peripheral artery disease or ankle-brachial index <0.9 at screening visit

          -  Exercise primarily limited by angina, lung disease or neuromuscular disease

          -  Systolic blood pressure <100 or >160 mmHg

          -  Heart rate <50 or >110 min-1

          -  Estimated glomerular filtration rate <30 ml/min

          -  Liver function tests >3 times upper limit of normal

          -  Serum phosphate below normal limit

          -  Pregnant or breast-feeding women

          -  Women of child-bearing potential unwilling to use recommended contraception methods
             during the study

          -  Treatment with oral iron supplements (except multivitamins) in past year

          -  Treatment with intravenous iron in past year

          -  Treatment with erythropoiesis stimulating agents in the past year

          -  Known intolerance of intravenous iron

          -  History of anaphylaxis

          -  Participation in another clinical trial within last 30 days.