Iron Stores and Skeletal Muscle Metabolism in Chronic Heart Failure

Chronic Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02737995
• Other study ID #: 15-00396
• Status: Completed
• Phase: Phase 1
• First received: April 8, 2016
• Last updated: August 12, 2016
• Start date: May 2015

Study information

• Verified date: August 2016
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 80 Years

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
New York University School of Medicine

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No