A Study of Ferric Citrate to Improve Inflammation and Lipid Levels

Phase 4

Terminated

Conditions: End Stage Renal Disease
Hyperphosphatemia
Chronic Inflammation

Interventions: Drug: Ferric Citrate

Registration Number: NCT02661295

Lead Sponsor: Winthrop University Hospital

Brief Summary: The risk of cardiovascular mortality in patients with end stage renal disease on hemodialysis is 10-100 times higher than the normal population. This is due in part to high levels of inflammation and vascular calcification found in these patients. Phosphate binders, particularly non-calcium based phosphate binders, may decrease cardiovascular risk by decreasing inflammation and vascular calcification. Ferric citrate a non-calcium based phosphate binder with approximately 210 mg of ferric iron has recently been approved for patients on hemodialysis. The effect of this phosphate binder on inflammation and lipid levels is unknown but investigators hypothesize that ferric citrate has the potential to improve inflammation and lipid levels in patients on hemodialysis by decreasing intravenous iron requirements and by improving lipid metabolism.

Detailed Description: In patients with end stage renal disease (ESRD) receiving dialysis, the risk of cardiovascular death has been estimated to be 10-100 times higher than the general population without renal disease. This is due in part to high levels of inflammation and vascular calcification (large deposits of calcium in arteries) found in these patients. Chronic inflammation is particularly common in patients with ESRD. Parenteral iron therapy, which is common in patients on dialysis, may contribute to this inflammation and also a higher cardiovascular risk. Phosphate binders, particularly non-calcium based phosphate binders, may decrease cardiovascular risk by decreasing inflammation and vascular calcification. In a study of 10,044 hemodialysis patients, treatment with a phosphate binder was associated with improved survival. Ferric citrate a non-calcium based phosphate binder with approximately 210 mg of ferric iron has recently been approved for patients on hemodialysis. It has been shown to improve serum phosphorus levels and decrease intravenous iron requirements for patients on hemodialysis. The effect of this phosphate binder on inflammation and lipid levels is unknown but investigators hypothesize that ferric citrate has the potential to improve inflammation and lipid levels in patients on hemodialysis by decreasing intravenous iron requirements and by improving lipid metabolism.

Ferric citrate has the potential to decrease cardiovascular risk through multiple mechanisms:

1. acting as a non-calcium based binder to decrease serum phosphorus levels and vascular calcification,

2. decreasing intravenous iron requirements which in turn may decrease inflammation,

3. binding endotoxin (a harmful substance produced by microorganisms) in the gut and

4. improving lipid metabolism.

The purpose of this study is to examine the effect of ferric citrate on inflammatory markers and lipid levels.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Hemodialysis treatment for ≥ 6 months
Phosphate binder treatment for ≥ to 1 month
Maintenance iron therapy with no more than 125mg IV iron weekly≥ to 1 month
Serum phosphorus levels between 2.5 and 8 at screening
Serum phosphorus ≥ to 6.0 mg/dL after a 2 week washout period.
Serum ferritin ≥ 200 and < 600ng/ml after a 2 week washout period
Serum calcium levels within normal range
Predicted survival greater than 6 months

Exclusion Criteria

Intact PTH< 70 pg/ml or > 1,000 pg/ml
Oral iron use
Vitamin C supplement use
Parathyroidectomy
Active malignancy
Hemodialysis via an intravenous catheter or arteriovenous (AV) graft
Received > 250mg of IV iron over the two weeks prior to screening
Whole blood transfusion within 3 months prior to screening
Active bleeding other than from the dialysis access
Hospitalization within one month prior to screening
current infection
Ongoing or uncontrolled inflammatory disorder
Liver cirrhosis
Likelihood of imminent renal transplantation

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ferric Citrate	Ferric Citrate	Ferric citrate at a starting dose of 2 tablets with each meal will be given to all participants.

Primary Outcome Measures

Name	Time	Method
Percent Change in Homocysteine	Baseline, Month 6	Percent change in homocysteine (micromol/L) from baseline to Month 6.
Percent Change in Total Cholesterol	Baseline, Month 6	Percent change in total cholesterol (mg/dl) from Baseline to Month 6.
Percent Change in LDL-Cholesterol	Baseline, Month 6	Percent change in low-density lipoprotein (LDL) cholesterol (mg/dl) from baseline to Month 6
Percent Change in HDL Cholesterol	Baseline, Month 6	Percent change in high-density lipoprotein (HDL) cholesterol (mg/dl) from baseline to Month 6.
Percent Change in Triglycerides	Baseline, Month 6	Percent change in triglycerides (mg/dl) from baseline to Month 6.
Percent Change in TNF-alpha	Baseline, Month 6	Percent change in tumor necrosis factor (TNF)-alpha (pg/ml) from Baseline to Month 6.
Percent Change in IL-6	Baseline, Month 6	Percent change in interleukin 6 (IL-6) (pg/ml) from baseline to Month 6
Percent Change in Ferritin	Baseline, Month 6	Percent change in ferritin (ng/ml) from baseline to Month 6.
Percent Change in C-reactive Protein	Baseline, Month 6	Percent change in C-reactive Protein (mg/L) from baseline to Month 6.
Percent Change in IL-8	Baseline, Month 6	Percent change in interleukin 8 (IL-8) (pg/ml) from baseline to Month 6.
Change in Intravenous Iron Use	Baseline, Month 6	Change in intravenous iron use (mg) from Baseline to Month 6.

Secondary Outcome Measures

Name	Time	Method
Percent Change in Calcium	Baseline, Month 6	Percent change in calcium (mg/dL) from baseline to Month 6.
Percent Change in Phosphorus	Baseline, Month 6	Percent change in phosphorus (md/dl) from baseline to Month 6.
Percent Change in Parathyroid Hormone (PTH)	Baseline, Month 6	Percent change in PTH (pg/ml) from baseline to Month 6.