Chronic Kidney DiseaseEarly Phase 1NCT01988116
Effects of Vitamin D Replacement on Hormones Regulating Iron Metabolism in Individuals With Chronic Kidney Disease
A Early Phase 1 study testing Oral Calcitriol 0.5 mcg once daily for 6 weeks in people with Chronic Kidney Disease and Anemia of Chronic Disease, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Chronic Kidney Disease, Anemia of Chronic Disease
- What is being tested?
- Oral Calcitriol 0.5 mcg once daily for 6 weeks
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Jun 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- Subjects with iron deficiency anemia defined as serum ferritin <100ng/ml and Transferring Saturation < 20%.
- Pregnancy and lactation.
- Subjects with hypercalcemia defined as serum calcium level of > 10.0 mg/dL.
- Subjects with serum phosphorus concentration of > 4.5 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Vitamin D Replacement in Chronic Kidney Disease and Its Effects on Iron Homeostasis, Serum Hepcidin, and Hemojuvelin Levels.
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.
Read more
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.
Read the 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.
- Conditions
- Chronic Kidney Disease, Anemia of Chronic Disease
- Being tested
- Oral Calcitriol 0.5 mcg once daily for 6 weeks, Placebo
- Keywords
- Chronic kidney disease, Anemia of chronic disease, Iron Metabolism, Iron Homeostasis, Vitamin D, Calcitriol, hemojuvelin, hepcidin, anemia, ferroportin
- Medical subject headings
- Renal Insufficiency, Chronic, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Calcitriol 0.5 mcg once daily for 6 weeksDrug
Also called Rocaltrol
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Oral Calcitriol | Experimental | Oral Calcitriol 0.5 mcg once daily for 6 weeks Receives: Drug: Oral Calcitriol 0.5 mcg once daily for 6 weeks |
| Placebo Arm | Placebo comparator | Placebo capsule 1 Capsule once daily for 6 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum hepcidin levels
Measured: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Change in soluble hemojuvelin
Measured: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Change in other indices of iron metabolism
Including, Serum Ferritin, Iron level, Percent transferrin saturation and TIBC
Measured: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Secondary outcomes (1)
Change in serum hemoglobin
Measured: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2013 (estimated)
- Study startOct 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bhupesh Panwar, MD, Principal investigator, University of Alabama, Nephrology DivisionOrlando M Gutierrez, MD,MMSc, Study director, University of Alabama, Nephrology Division
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01988116
- Sponsor's protocol ID
- F130725013
- Status last verified
- Aug 2015
- First submitted
- 4 Nov 2013
- Last updated
- 24 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Panwar B, McCann D, Olbina G, Westerman M, Gutierrez OM. Effect of calcitriol on serum hepcidin in individuals with chronic kidney disease: a randomized controlled trial. BMC Nephrol. 2018 Feb 9;19(1):35. doi: 10.1186/s12882-018-0823-7.
PubMed 29426300
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Replacement in Chronic Kidney Disease and Its Effects on Iron Homeostasis, Serum Hepcidin, and Hemojuvelin Levels.
- ClinicalTrials.gov ID
- NCT01988116
- Acronym / sponsor ID
- F130725013
- Conditions
- Chronic Kidney Disease, Anemia of Chronic Disease
- Keywords
- Chronic kidney disease, Anemia of chronic disease, Iron Metabolism, Iron Homeostasis, Vitamin D, Calcitriol, hemojuvelin, hepcidin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 20 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Calcitriol | Experimental | Drug: Oral Calcitriol 0.5 mcg once daily for 6 weeksOral Calcitriol 0.5 mcg once daily for 6 weeks |
| Placebo Arm | Placebo comparator | Drug: PlaceboPlacebo capsule 1 Capsule once daily for 6 weeks |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Calcitriol 0.5 mcg once daily for 6 weeksAlso: Rocaltrol | Drug | Oral Calcitriol |
| Placebo | Drug | Placebo Arm |
Primary outcome
Change in serum hepcidin levels
Time frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Change in soluble hemojuvelin
Time frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Change in other indices of iron metabolism
Time frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Including, Serum Ferritin, Iron level, Percent transferrin saturation and TIBC
1 secondary outcome
Change in serum hemoglobin
Time frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2015.
- Derived from this study: PubMed 29426300Panwar B, McCann D, Olbina G, Westerman M, Gutierrez OM. Effect of calcitriol on serum hepcidin in individuals with chronic kidney disease: a randomized controlled trial. BMC Nephrol. 2018 Feb 9;19(1):35. doi: 10.1186/s12882-018-0823-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bhupesh Panwar, MD principal investigator
University of Alabama, Nephrology Division
Orlando M Gutierrez, MD,MMSc study director
University of Alabama, Nephrology Division
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Oral Calcitriol 0.5 mcg once daily for 6 weeks in people with Chronic Kidney Disease and Anemia of Chronic Disease, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in serum hepcidin levels (time frame: At Day 0, Day 3, 1 week, 4 weeks and 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01988116, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2015.