Trial record 9 of 224 for:    Open Studies | "Chronic Disease"

Effects of Vitamin D Replacement on Hormones Regulating Iron Metabolism in Individuals With Chronic Kidney Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
Bhupesh Panwar, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01988116
First received: November 4, 2013
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

The purpose of the study is to learn more about how treatment with vitamin D can affect iron metabolism and blood levels of two hormones that control iron levels, hepcidin and hemojuvelin in people with chronic kidney disease (CKD).

Iron is an essential mineral which is a major component of proteins that carry oxygen in the blood. Problems with iron metabolism can lead to low blood levels (anemia), which can commonly happen in people with CKD.

New research over the last decade has uncovered a new hormone called `hepcidin', which is made in the liver and released into the blood. Hepcidin controls how much iron is in the blood by preventing the absorption of iron from food. Blood levels of hepcidin C are found to be high in people with CKD, and a recent small study in people with normal kidney function showed that treatment with vitamin D decreased hepcidin levels.

Another protein, known as `hemojuvelin', has been recently discovered and is also thought to control the amount of iron in the blood. The relationship between vitamin D and hemojuvelin has never been studied before.

In this study, investigators would like to examine the effects of vitamin D on iron metabolism and blood levels of hepcidin C and hemojuvelin in individuals with CKD.


Condition Intervention Phase
Chronic Kidney Disease
Anemia of Chronic Disease
Drug: Oral Calcitriol 0.5 mcg once daily for 6 weeks
Drug: Placebo
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Vitamin D Replacement in Chronic Kidney Disease and Its Effects on Iron Homeostasis, Serum Hepcidin, and Hemojuvelin Levels.

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Change in serum hepcidin levels [ Time Frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks ] [ Designated as safety issue: No ]
  • Change in soluble hemojuvelin [ Time Frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks ] [ Designated as safety issue: No ]
  • Change in other indices of iron metabolism [ Time Frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks ] [ Designated as safety issue: No ]
    Including, Serum Ferritin, Iron level, Percent transferrin saturation and TIBC


Secondary Outcome Measures:
  • Change in serum hemoglobin [ Time Frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: October 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Calcitriol
Oral Calcitriol 0.5 mcg once daily for 6 weeks
Drug: Oral Calcitriol 0.5 mcg once daily for 6 weeks
Other Name: Rocaltrol
Placebo Comparator: Placebo Arm
Placebo capsule 1 Capsule once daily for 6 weeks
Drug: Placebo

Detailed Description:

Iron homeostasis is tightly regulated in humans. Iron is mostly recycled from hemoglobin, myoglobin and other enzymes. Since humans lack the capacity to excrete excess iron, it must be intricately regulated at the site of its absorption in the duodenum and proximal jejunum. In the last decade, hepcidin has emerged as a master regulator of iron homeostasis. It decreases iron absorption from the gut mucosa by limiting its transport from the enterocyte across the basolateral membrane into the circulation. It does so by down-regulating the synthesis or promoting internalization of a basolateral membrane protein `Ferroportin', the only known cellular iron exporter.

Vitamin D is hypothesized to exert a significant and independent effect on the iron metabolism. In the CKD population, low vitamin-D levels independently correlate with the severity of anemia. Hepcidin C levels are found to be elevated in the CKD population. Mechanisms underlying the effect of vitamin D on iron homeostasis potentially include vitamin D induced expression of erythropoietin receptors, increased proliferation of erythroid precursors, and reduction in hepcidin C levels due to reduction in IL-6 from the anti-inflammatory effects of vitamin D. More recently, a study revealed direct relationship between vitamin D replacement and a sustained fall in hepcidin C levels. The same group of researchers found the above relationship to be due to a direct effect of vitamin D on hepcidin expression.

Hemojuvelin (HJV) is a protein encoded by the HFE2 gene and is found in the membrane bound and the soluble form (sHJV) in the humans. Mutations in the HJV gene are responsible for Juvenile Hemochromatosis. It is an upstream regulator of hepcidin transcription and appears to be essential for hepcidin expression in the hepatocytes and has important role to play in iron homeostasis. Recently, an assay has become available to measure the sHJV levels in the serum.

Although, we know that hepcidin plays a central role in iron homeostasis and recent studies have given us insight into the role hemojuvelin and vitamin D play in iron metabolism, to date, no studies have examined the effect on vitamin D replacement on hepcidin, hemojuvelin levels and iron metabolism in individuals with CKD.

Hypothesis 1: Treatment with an activated vitamin D analog in the individuals with CKD results in a statistically significant fall in hepcidin C levels as compared to individuals provided with placebo.

Hypothesis 2: Treatment with an activated vitamin D analog results in decreased levels of soluble hemojuvelin in individuals with chronic kidney disease.

Hypothesis 3: Vitamin D replacement in the individuals with CKD results in improved iron parameters as compared to the placebo.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with mild to moderate CKD (eGFR 15 - 60 ml/min/1.73 m2) as estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula.

Exclusion Criteria:

  • Subjects currently receiving active vitamin D analog therapy or history of recent (< 3 months) use.
  • Subjects currently receiving nutritional vitamin D (cholecalciferol or ergocalciferol) in dosages greater than 2000 IU/day.
  • Subjects receiving erythropoiesis stimulating agents.
  • Subjects receiving intravenous iron therapy.
  • Subjects receiving oral iron therapy started within 3 months prior to recruitment.
  • Subjects with severe anemia defined as Hb < 8.0 g/dL for males and Hb <7.0 g/dL for females.
  • Subjects with iron deficiency anemia defined as serum ferritin <100ng/ml and Transferring Saturation < 20%.
  • Males with Hb > 13 g/dL or Females with Hb > 12 g/dL.
  • Pregnancy and lactation.
  • Subjects with hypercalcemia defined as serum calcium level of > 10.0 mg/dL.
  • Subjects with serum phosphorus concentration of > 4.2 mg/dL.
  • Subjects with acute kidney injury or rapidly declining GFR.
  • Subjects receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, and patients with renal transplant.
  • Subjects with focus of active inflammation or infection determined clinically.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01988116

Contacts
Contact: Bhupesh Panwar, MD 2053291252 bhupesh@uab.edu
Contact: Orlando M Gutierrez, MD,MMSc 2059962736 ogutierr@uab.edu

Locations
United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Bhupesh Panwar, MD University of Alabama, Nephrology Division
Study Director: Orlando M Gutierrez, MD,MMSc University of Alabama, Nephrology Division
  More Information

No publications provided

Responsible Party: Bhupesh Panwar, MD, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01988116     History of Changes
Other Study ID Numbers: F130725013
Study First Received: November 4, 2013
Last Updated: November 19, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Chronic kidney disease
Anemia of chronic disease
Iron Metabolism
Iron Homeostasis
Vitamin D
Calcitriol
hemojuvelin
hepcidin
anemia
ferroportin

Additional relevant MeSH terms:
Chronic Disease
Anemia
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Hematologic Diseases
Disease Attributes
Pathologic Processes
Urologic Diseases
Renal Insufficiency
Calcitriol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014