Iron Deficiency and FGF23 Regulation in CKD and HF (INDIGO)

Iron Deficiency and Fibroblast Growth Factor 23 Regulation in Chronic Kidney Disease and Heart Failure

This study investigates the effects of intravenous (IV) iron sucrose therapy on blood levels of Fibroblast Growth Factor 23 (FGF23, a protein that regulates the amount of phosphate in the body) in iron deficiency anemia in healthy participants, participants with Congestive Heart Failure (CHF, where the heart does not pump adequate blood supply to the body), participants with Chronic Kidney Disease (CKD, where the kidney function is reduced), and participants with CKD and CHF.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Chronic Heart Failure; Iron Deficiency Anemia
• Intervention / Treatment: Drug: Iron Sucrose

Detailed Description

Iron is a key part of our red blood cells which bring oxygen to our body's tissues. Without iron, our blood cannot carry oxygen. The body normally gets iron through diet and it also re-uses iron from old red blood cells. When iron stores are low, patients get iron deficiency anemia. This can happen because patients lose more red blood cells and iron than the body can replace, the body does not do a good job at absorbing iron from the diet, or the body is able to absorb iron but patients are not getting enough iron from their diets. Many patients with chronic diseases such as CKD and CHF also have iron deficiency anemia.

Iron deficiency may also cause a hormone in the body named FGF23 to rise. FGF23 is a hormone that is made in bone and has an important role in the heart and kidney. When the kidneys are not working properly, as in CKD, or when the heart is not pumping correctly, as in CHF, FGF23 levels in the blood go up. Many patients with CKD or CHF also have low levels of iron. In these cases, FGF23 levels may rise even more. Too much FGF23 in the blood may lead to an increased risk of heart problems and accelerate loss of kidney function. The best way to control FGF23 levels in the blood in CKD and CHF is not known.

The investigators are conducting a 6-week iron deficiency anemia study on healthy individuals,individuals with CKD, and individuals with CHF to find out if treating iron deficiency anemia with intravenous iron sucrose therapy can safely and successfully lower FGF23 levels. Iron sucrose has been shown to lower FGF23 in animal models. The short term effects of iron sucrose on FGF23 levels in CKD and CHF are not known.

• Study Type: Observational
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients with iron deficiency anemia will be enrolled (those without CKD or HF, those with CKD only, those with HF only, and those with CKD/HF). They will be given iron sucrose as routine care for treatment of their iron deficiency anemia.

Description

Inclusion Criteria:

• Age ≥ 18 years old
• Ability to understand and the willingness to sign a written informed consent.
• Iron Deficiency Anemia, as defined by
• Ferritin level < 100 ng/ml or
• Transferrin saturation <20% with ferritin 100-350 ng/ml and
• Hemoglobin < 12 g/dl

Exclusion Criteria:

• Hypersensitivity to any component of iron sucrose
• Malignancy within 5 years
• End stage renal disease or kidney transplantation
• Erythropoiesis stimulating agents
• Red blood cell transfusions within last 60 days
• Current radiotherapy or chemotherapy
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than 1.5 times normal
• Hemochromatosis
• Chronic digestive diseases
• Pregnancy or nursing
• Active alcohol or drug abuse
• Uncontrolled hypertension
• Active infection
• Hospitalization in the 4 preceding weeks
• Concomitant use of antibiotics
• Concomitant use of immunosuppression
• Inability to consent.
• Conditions, in which of the opinion of the investigator, make participation unacceptable

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Iron Sucrose Treatment; All patients with iron deficiency anemia (those without CKD or HF, those with CKD only, those with HF only, and those with CKD/HF) will be given 5 weekly doses of 200 mg of intravenous iron sucrose.	Drug: Iron Sucrose; All participants will be given intravenous iron sucrose (200 mg) weekly for 5 weeks. Iron sucrose is infused over 60 minutes.; Other Names: Venofer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in c-terminal FGF23 measurements	longitudinal change in plasma c-terminal FGF23 (RU/ml) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Intact FGF23 measurements	longitudinal change in plasma intact FGF23 (pg/ml) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Parathyroid Hormone	longitudinal change in Serum Parathyroid Hormone (pg/ml) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Phosphate (mg/dl)	longitudinal change in Plasma Phosphate (mg/dl) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Serum creatinine	longitudinal change in Serum creatinine (mg/dl) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in 1,25 dihydroxyvitamin D	longitudinal change in 1,25 dihydroxyvitamin D (pg/ml) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in C-reactive protein	longitudinal change in C-reactive protein (mg/L) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Ferritin Measurement	longitudinal change in serum ferritin (ng/ml) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Iron Measurement	longitudinal change in Serum iron (ug/dl) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Transferrin Saturation	longitudinal change in Transferrin Saturation (%) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months
Change in Hemoglobin Measurement	longitudinal change in Serum hemoglobin (g/dl) over 6 weeks and 3 months	Weekly x 6 weeks, 1 longitudinal measurement at 3 months

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Kidney Foundation
• Investigators: Principal Investigator: Rupal Mehta, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: April 4, 2017
• First Posted (Actual): April 10, 2017

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Phosphate; Iron Deficiency; Fibroblast Growth Factor 23
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Heart Failure; Kidney Diseases; Renal Insufficiency, Chronic; Anemia, Iron-Deficiency; Hematinics; Ferric Oxide, Saccharated
• Other Study ID Numbers: STU00201742

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Individual participant data will not be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No