Kidney DiseasePOSH-DNCT00781417
Prevention of Secondary Hyperparathyroidism With Vitamin D in Stage II/III Chronic Kidney Disease
A study testing Vitamin D in people with Kidney Disease, run by Atlanta VA Medical Center at 1 site in United States.
Trial summary
This study will evaluate whether earlier intervention with vitamin D in stage II/III chronic kidney disease will prevent or delay secondary hyperparathyroidism. Subjects will receive vitamin D or placebo at study entry and will be followed for a period of one year. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Kidney Disease
- What is being tested?
- Vitamin D
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Dec 2011
- Phase
- Interventional
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Study subjects must be patients with CKD stage II/III (estimated glomerular filtration rate, 30-90 ml/min/1.73m body surface area), 25-hydroxyvitamin D (25(OH) D) level >10 ng/ml documented in the medical record for the past 6 months.
- Estimated Glomerular Filtration Rate will be calculated by using the original Modification of Diet in Renal Disease Study equation (online at http://www.nkdep.nih.gov)(16)
- Study subjects must agree to participate in the study and provide written informed consent
- Histology: not applicable
- Sites: Atlanta VA Medical Center
- Stage of Disease: CKD stage II/III, who has 25-hydroxyvitamin D (25(OH)D) level >10 ng/ml, but less than 30 ng/ml
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- Age: Study subjects must be >18 but <85 years old
- Performance Status: Study subjects will be patients with CKD stage II/III (estimated glomerular filtration rate, 30-90 ml/min/1.73m body surface area), 25-hydroxyvitamin D (25(OH)D) level >10 ng/ml, but less than 30 ng/ml
- Informed consent requirements: All study subjects must agree to participate in the study and provide written informed consent, which will be written in English.
Who cannot join
- Age < 18years or >85 years old
- Prior other diseases: History of liver failure (AST or ALT >3 ULN), history of intestinal malabsorption or chronic diarrhea, corrected serum calcium >10.5 mg/dl, calcium x phosphorus product >70,treatment with more than 1000 IU of vitamin D per day; or current treatment with a vitamin D analogue or calcimimitec, taking antiepileptic medication, or other medications that could alter vitamin D metabolism(eg, phenytoin, phenobarbital, rifampin(17)
- Infection: not applicable
Trial locations and contacts
1 site in 1 country.
About this study
This study will evaluate whether earlier intervention with vitamin D in stage II/III chronic kidney disease will prevent or delay secondary hyperparathyroidism. Subjects will receive vitamin D or placebo at study entry and will be followed for a period of one year. The hypothesis is that subjects given vitamin D will have lower PTH and higher 25(OH)D after 1 year compared to placebo. Additionally, there will be less subjects who progress into secondary hyperparathyroidism in the vitamin D treated group compared to the placebo treated group.
Read the detailed description
Vitamin D is important to maintain normal calcium homeostasis and optimal bone health (1, 2). The synthesis of vitamin D and its metabolism to 1,25(OH)2D is regulated by parathyroid hormone (PTH), serum calcium, and phosphorus levels. In response to low serum calcium level, serum PTH activates alpha-1-hydroxylase for increased 1,25(OH)2D production in the kidney and also enhances tubular reabsorption of calcium (3). The higher levels of 1, 25(OH)2D results in increased intestinal calcium absorption (4). Increased serum phosphorus levels which occurs in the early stages of chronic kidney disease (CKD) results in inhibition of the 1-alpha-hydroxylase, which results in decreased 1, 25(OH)2 D production, decreased intestinal calcium absorption leading to secondary hyperparathyroidism with increased PTH levels. Circulating 1,25(OH)2D levels begin to fall when the glomerular filtration rate is less than 40 mL/min occasionally even less than 80 mL/min (11) and almost always significantly reduced in subjects with end-stage renal failure (12). Furthermore, in CKD, decreased renal mass also results in decreased expression of 1-alpha-hydroxlase and less production of 1,25(OH)2D which also exacerbates secondary hyperparathyroidism (5-7).
Therefore, in CKD there are three processes that lead to secondary hyperparathyroidism. 1) decreased renal mass leading to decreased production of 1,25(OH)2D leading to a compensatory rise in PTH to further enhance production of 1,25(OH)2D 2) inhibition of the renal 1-alpha-hydroxylase by accumulating phosphorus levels leading to decreased 1,25(OH)2D which also leads to secondary hyperparathyroidism. 3) increased phosphorus leads to lower ionized calcium leading to increased parathyroid hormone secretion.
Untreated secondary hyperparathyroidism can lead to renal osteodystrophy (9) and increased mortality due to cardiovascular disease (10). Prolonged secondary hyperparathyroidism can lead to bone resorption and eventually autonomous parathyroid hormone secretion termed tertiary hyperparathyroidism.
Vitamin D status is one of the major factors that may prevent progression of secondary hyperparathyroidism in patients with CKD. Insufficient levels of 25-hydroxyvitamin D further exacerbate secondary hyperparathyroidism by not providing adequate substrate for the renal 1-alpha-hydroxylase for conversion to the active form of vitamin D, 1,25(OH)2D. A recent cross-sectional study on patients with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States has shown that only 29% and 17% of them had sufficient level, respectively (13). Vitamin D status is easily corrected. In our previous study we concluded that weekly cholecalciferol supplementation was an effective treatment to correct vitamin D status in patients with CKD stages III and IV (14). However, PTH levels did not return to normal. Therefore, it is likely that earlier intervention with vitamin D is necessary to prevent rather than to treat secondary hyperparathyroidism. This is the major question that is being evaluated in this study. Can intervening with vitamin D at an earlier stage of chronic kidney disease result in decreased incidence of secondary hyperparathyroidism?
2.0 Objectives
2.1 Overall Objective
The primary objective of this study is to assess that if improving and maintaining an optimal 25(OH) D level ( by National Kidney Foundation should be greater than 30ng/ml) (15) in people with stage II/III Chronic Kidney disease would delay the progression of secondary hyperparathyroidism and translate into improved markers of bone turnover
2.2 Specific Aims
Primary: 1) To determine in a double blind, randomized study whether supplementation with 50,000 IU of cholecalciferol (vitamin D3) given weekly for 12 weeks followed by maintenance cholecalciferol 50,000 IU every other week would improve and maintain vitamin D status in CKD patients stage 2/3 compared to placebo at 12 months.
- To determine whether early intervention with vitamin D therapy further decreases PTH levels after 12 weeks of therapy and 12 months of therapy.
Secondary: 1) To determine whether early treatment with vitamin D results in improving levels of bone turnover markers- tartrate-resistant acid phosphatase isoform 5b(TRAP5b), procollagen Type 1 N-Terminal propeptide (PINP), serum C-Telopeptide and Alkaline phosphatase.
- Conditions
- Kidney Disease
- Being tested
- Vitamin D, Placebo
- Keywords
- vitamin D, Chronic Kidney Disease, parathyroid hormone, Chronic kidney disease Stage II and III
- Medical subject headings
- Kidney Diseases, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin DDietary supplement
Also called cholecalciferol, vitamin D3
50,000 IU once a week for 12 weeks then every other week for 40 weeks
PlaceboOther
Matching Placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Cholecalciferol 50,000 IU once a week for 12 weeks then every other week for 40 weeks Receives: Dietary Supplement: Vitamin D |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
25(OH)D
Measured: 52 weeks
Parathyroid Hormone
Measured: 52 weeks
24 hour urine calcium
Measured: 52 weeks
Secondary outcomes (1)
Markers of bone turnover
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionOct 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney DiseaseStudies of the same condition, open and under way.
- 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
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atlanta VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Emory University
- Responsible party
- Principal investigator, Vin Tangpricha, Atlanta VA Medical Center
- Investigators
- Vin Tangpricha, MD, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00781417
- Sponsor's protocol ID
- Atlanta VAMC
- Acronym
- POSH-D
- Status last verified
- Feb 2012
- First submitted
- 28 Oct 2008
- Last updated
- 7 Feb 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Secondary Hyperparathyroidism With Vitamin D in Stage II/III Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT00781417
- Acronym / sponsor ID
- POSH-D / Atlanta VAMC
- Conditions
- Kidney Disease
- Keywords
- vitamin D, Chronic Kidney Disease, parathyroid hormone, Chronic kidney disease Stage II and III
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Atlanta VA Medical CenterUS federal agency
- Collaborators
- Emory University
- Study start
- Oct 2008
- Primary completion
- Oct 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 29 Oct 2008 (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.
This study will evaluate whether earlier intervention with vitamin D in stage II/III chronic kidney disease will prevent or delay secondary hyperparathyroidism. Subjects will receive vitamin D or placebo at study entry and will be followed for a period of one year. The hypothesis is that subjects given vitamin D will have lower PTH and higher 25(OH)D after 1 year compared to placebo. Additionally, there will be less subjects who progress into secondary hyperparathyroidism in the vitamin D treated group compared to the placebo treated group.
Detailed description
Vitamin D is important to maintain normal calcium homeostasis and optimal bone health (1, 2). The synthesis of vitamin D and its metabolism to 1,25(OH)2D is regulated by parathyroid hormone (PTH), serum calcium, and phosphorus levels. In response to low serum calcium level, serum PTH activates alpha-1-hydroxylase for increased 1,25(OH)2D production in the kidney and also enhances tubular reabsorption of calcium (3). The higher levels of 1, 25(OH)2D results in increased intestinal calcium absorption (4). Increased serum phosphorus levels which occurs in the early stages of chronic kidney disease (CKD) results in inhibition of the 1-alpha-hydroxylase, which results in decreased 1, 25(OH)2 D production, decreased intestinal calcium absorption leading to secondary hyperparathyroidism with increased PTH levels. Circulating 1,25(OH)2D levels begin to fall when the glomerular filtration rate is less than 40 mL/min occasionally even less than 80 mL/min (11) and almost always significantly reduced in subjects with end-stage renal failure (12). Furthermore, in CKD, decreased renal mass also results in decreased expression of 1-alpha-hydroxlase and less production of 1,25(OH)2D which also exacerbates secondary hyperparathyroidism (5-7).
Therefore, in CKD there are three processes that lead to secondary hyperparathyroidism. 1) decreased renal mass leading to decreased production of 1,25(OH)2D leading to a compensatory rise in PTH to further enhance production of 1,25(OH)2D 2) inhibition of the renal 1-alpha-hydroxylase by accumulating phosphorus levels leading to decreased 1,25(OH)2D which also leads to secondary hyperparathyroidism. 3) increased phosphorus leads to lower ionized calcium leading to increased parathyroid hormone secretion.
Untreated secondary hyperparathyroidism can lead to renal osteodystrophy (9) and increased mortality due to cardiovascular disease (10). Prolonged secondary hyperparathyroidism can lead to bone resorption and eventually autonomous parathyroid hormone secretion termed tertiary hyperparathyroidism.
Vitamin D status is one of the major factors that may prevent progression of secondary hyperparathyroidism in patients with CKD. Insufficient levels of 25-hydroxyvitamin D further exacerbate secondary hyperparathyroidism by not providing adequate substrate for the renal 1-alpha-hydroxylase for conversion to the active form of vitamin D, 1,25(OH)2D. A recent cross-sectional study on patients with moderate to severe CKD not yet on dialysis therapy from 12 geographically diverse regions of the United States has shown that only 29% and 17% of them had sufficient level, respectively (13). Vitamin D status is easily corrected. In our previous study we concluded that weekly cholecalciferol supplementation was an effective treatment to correct vitamin D status in patients with CKD stages III and IV (14). However, PTH levels did not return to normal. Therefore, it is likely that earlier intervention with vitamin D is necessary to prevent rather than to treat secondary hyperparathyroidism. This is the major question that is being evaluated in this study. Can intervening with vitamin D at an earlier stage of chronic kidney disease result in decreased incidence of secondary hyperparathyroidism?
2.0 Objectives
2.1 Overall Objective
The primary objective of this study is to assess that if improving and maintaining an optimal 25(OH) D level ( by National Kidney Foundation should be greater than 30ng/ml) (15) in people with stage II/III Chronic Kidney disease would delay the progression of secondary hyperparathyroidism and translate into improved markers of bone turnover
2.2 Specific Aims
Primary: 1) To determine in a double blind, randomized study whether supplementation with 50,000 IU of cholecalciferol (vitamin D3) given weekly for 12 weeks followed by maintenance cholecalciferol 50,000 IU every other week would improve and maintain vitamin D status in CKD patients stage 2/3 compared to placebo at 12 months.
- To determine whether early intervention with vitamin D therapy further decreases PTH levels after 12 weeks of therapy and 12 months of therapy.
Secondary: 1) To determine whether early treatment with vitamin D results in improving levels of bone turnover markers- tartrate-resistant acid phosphatase isoform 5b(TRAP5b), procollagen Type 1 N-Terminal propeptide (PINP), serum C-Telopeptide and Alkaline phosphatase.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Dietary Supplement: Vitamin DCholecalciferol 50,000 IU once a week for 12 weeks then every other week for 40 weeks |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Study subjects must be patients with CKD stage II/III (estimated glomerular filtration rate, 30-90 ml/min/1.73m body surface area), 25-hydroxyvitamin D (25(OH) D) level >10 ng/ml documented in the medical record for the past 6 months.
- Estimated Glomerular Filtration Rate will be calculated by using the original Modification of Diet in Renal Disease Study equation (online at http://www.nkdep.nih.gov)(16)
- Study subjects must agree to participate in the study and provide written informed consent
- Histology: not applicable
- Sites: Atlanta VA Medical Center
Key exclusion criteria (3 listed)
- Age < 18years or >85 years old
- Prior other diseases: History of liver failure (AST or ALT >3 ULN), history of intestinal malabsorption or chronic diarrhea, corrected serum calcium >10.5 mg/dl, calcium x phosphorus product >70,treatment with more than 1000 IU of vitamin D per day; or current treatment with a vitamin D analogue or calcimimitec, taking antiepileptic medication, or other medications that could alter vitamin D metabolism(eg, phenytoin, phenobarbital, rifampin(17)
- Infection: not applicable
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 |
|---|---|---|
| Vitamin DAlso: cholecalciferol, vitamin D350,000 IU once a week for 12 weeks then every other week for 40 weeks | Dietary supplement | 1 |
| PlaceboMatching Placebo | Other | Placebo |
Primary outcome
25(OH)D
Time frame: 52 weeks
Parathyroid Hormone
Time frame: 52 weeks
24 hour urine calcium
Time frame: 52 weeks
1 secondary outcome
Markers of bone turnover
Time frame: 52 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 7 Feb 2012.
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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.
Vin Tangpricha, MD, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin D in people with Kidney Disease, run by Atlanta VA Medical Center 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 9 inclusion and 3 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 7 Feb 2012. 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.
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?
25(OH)D (time frame: 52 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?
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 7 Feb 2012.