Iron Stores and Skeletal Muscle Metabolism in Chronic Heart Failure

A Pilot Feasibility Study on Iron Stores and Skeletal Muscle Metabolism in Chronic Heart Failure

Iron deficiency may contribute to exercise intolerance by altering mitochondrial oxidative capacity in skeletal muscle. Functional iron deficiency is common in heart failure patients, but the relationship to exercise intolerance and mitochondrial oxidative capacity is unknown. This is a pilot study to determine the feasibility of the use of specialized 31P-MRS and MRI techniques for measurement of skeletal muscle bioenergetics in patients with heart failure with and without functional iron deficiency.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Ferric carboxymaltose infusion

Detailed Description

This study will obtain pilot feasibility data to explore the relationship between blood biomarkers of functional iron deficiency and skeletal muscle mitochondrial oxidative capacity with 31P-magnetic resonance spectroscopy (MRS) and imaging in heart failure patients.

Twenty (20) subjects will be recruited from the clinical practice of the NYU Advanced Cardiac Therapeutics group at NYU Langone Medical Center.

Twenty (20) subjects will be recruited from the practice of the NYU Advanced Cardiac Therapeutics group at NYU Langone Medical Center. The study will require a maximum of four (4) visits over a period of five (5) weeks. Eligibility for Visits 2-4 will be determined by the screening criteria in Visit 1. It is anticipated that 50% of the screened subjects at Visit 1 will be eligible to participate in Visit 2. Eligibility for participation in Visits 3 and 4 will be determined by the results of the iron biomarkers obtained at Visit 2. We anticipate that 50% of the subjects at Visit 2 will be eligible to participate in Visits 3 and 4. Only subject with functional iron deficiency will participate in Visits 3 and 4. There is no clinical care component for this study.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able and willing to provide written informed consent
• Age 21-80 years
• Chronic heart failure >3 months with NYHA Class I-III symptoms

Exclusion Criteria:

• Presence of implantable defibrillator, permanent pacemaker not designed for safe use in 3T MRI stud
• Metallic implant or implants that are deemed not suitable for MRI scan on 3T
• Aneurysm clips, cochlear implants, presence of shrapnel in strategic locations, and metal in the eye
• Known claustrophobia or any other history of intolerance of MRI procedure
• Treated diabetes mellitus or hemoglobin A1c (HbA1c) >6.5%
• Any hospitalization <60 days
• Myocardial infarction or stroke < 6 months
• Estimated glomerular filtration rate <30 ml/min
• Weight <50 or >120 kg
• Systolic blood pressure <90 mmHg or > 160 mmHg
• Heart rate <50 or >100 beats per minute
• Resting oxygen saturation on room air <92%
• Hemoglobin <11 g/dl
• Serum phosphate below normal range (<2.4 mg/dl)
• Liver function tests (AST, ALT, Alk Phos, or Total Bilirubin) >twice upper limit of normal range
• Pregnancy or current breastfeeding
• Exercise limitation primarily due to valvular heart disease, lung disease, neuromuscular disease, or joint disease
• History of asthma
• History of anaphylaxis
• Known history of intolerance to any formulation of intravenous iron

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Iron Replacement

Drug: Ferric carboxymaltose infusion; Subjects with functional iron deficiency determined by the results of iron biomarker results at Visit 2 will receive a single dose of intravenous ferric carboxymaltose . The dose of Injectafer will be calculated from a modified Ganzoni equation adapted from previous heart failure clinical trials The maximum dose of Injectafer will be 750 mg. The calculated dose of Injectafer will be diluted in normal saline solution (4 mg/ml) and administered via a volumetric pump administered over 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of iron stores	Plantar flexion exercise as determined with a novel dynamic phosphorus magnetic resonance spectroscopy and imaging technique (31P-MRS & MRI) in heart failure patients (n=10) with and without functional iron deficiency. A spectrally selective three-dimensional turbo spin echo (3D-TSE) echo (3D-TSE) protocol for measurement of phosphocreatine recovery kinetics on a 3T Siemens MRI scanner as previously described (Siemens Medical Solutions, Erlangen, Germany).	60 minutes
Skeletal muscle bioenergetics using 31P- MRS Spectroscopy	Plantar flexion exercise with 31P-MRS and MRI in heart failure patients (n=5) with functional iron deficiency. A spectrally selective three-dimensional turbo spin echo (3D-TSE) protocol for measurement of phosphocreatine recovery kinetics on a 3T Siemens MRI scanner (Siemens Medical Solutions, Erlangen, Germany). protocol for measurement of phosphocreatine recovery kinetics on a 3T Siemens MRI scanner as previously described (Siemens Medical Solutions, Erlangen, Germany).	120 Minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Capacity	Subjects will be asked to walk along a 30 meter marked path in a corridor at a self-selected pace. Subjects will receive standardized instruction before and during the walking test. The distance walked after 6 minutes (meters) will be recorded.	Six Minutes

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Stuart Katz, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: April 8, 2016
• First Submitted That Met QC Criteria: April 8, 2016
• First Posted (Estimate): April 14, 2016

Study Record Updates

• Last Update Posted (Estimate): August 15, 2016
• Last Update Submitted That Met QC Criteria: August 12, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Iron deficiency
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 15-00396