- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00781417
Prevention of Secondary Hyperparathyroidism With Vitamin D in Stage II/III Chronic Kidney Disease (POSH-D)
Study Overview
Status
Conditions
Intervention / Treatment
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.
2) 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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30300
- Atlanta VAMC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Matching Placebo
|
Active Comparator: 1
Cholecalciferol 50,000 IU once a week for 12 weeks then every other week for 40 weeks
|
50,000 IU once a week for 12 weeks then every other week for 40 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
25(OH)D
Time Frame: 52 weeks
|
52 weeks
|
Parathyroid Hormone
Time Frame: 52 weeks
|
52 weeks
|
24 hour urine calcium
Time Frame: 52 weeks
|
52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Markers of bone turnover
Time Frame: 52 weeks
|
52 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Vin Tangpricha, MD, PhD, Emory University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Urologic Diseases
- Endocrine System Diseases
- Renal Insufficiency
- Parathyroid Diseases
- Kidney Diseases
- Renal Insufficiency, Chronic
- Hyperparathyroidism
- Hyperparathyroidism, Secondary
- Physiological Effects of Drugs
- Micronutrients
- Bone Density Conservation Agents
- Calcium-Regulating Hormones and Agents
- Vitamin D
- Cholecalciferol
- Vitamins
- Ergocalciferols
Other Study ID Numbers
- Atlanta VAMC
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Kidney Disease
-
3-C Institute for Social DevelopmentUniversity of North Carolina, Chapel HillCompletedChronic Kidney Diseases | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage4 | Pediatric Kidney Disease | Chronic Kidney Disease stage3 | Chronic Kidney Disease Stage V | Chronic Kidney Disease, Stage IV (Severe) | Chronic Kidney Disease Stage 2 | Chronic Kidney Disease, Stage IUnited States
-
National Taiwan University HospitalCompletedChronic Kidney Disease stage4 | Chronic Kidney Disease stage3 | Chronic Kidney Disease Stage 2 | Chronic Kidney Disease Stage 1Taiwan
-
Universiti Putra MalaysiaRecruitingChronic Kidney Diseases | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage4 | Chronic Kidney Disease stage3 | Chronic Kidney Disease Requiring Chronic DialysisMalaysia
-
Centre Hospitalier le MansLe Mans UniversiteWithdrawnFatigue | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage3 | Chronic Kidney Failure | Chronic Kidney Disease, Stage 4 (Severe)
-
A.C. AbrahamsCompletedEnd Stage Renal Disease | Chronic Kidney Disease | End Stage Kidney Disease | Chronic Kidney FailureNetherlands
-
Centre Hospitalier le MansLe Mans UniversiteRecruitingFatigue | Chronic Kidney Disease Stage 5 | Chronic Kidney Disease stage4 | Chronic Kidney Disease Stage 3BFrance
-
University of UtahNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)RecruitingHemodialysis | Kidney Disease, Chronic | Kidney Failure | Dialysis | Diabetic | End-stage Kidney Disease | Kidney Dysfunction | Non-diabeticUnited States
-
AbbottTerminatedEnd-Stage Kidney DiseaseUnited States
-
European Society of Intensive Care MedicineCompletedAcute Kidney Injury | Renal Replacement Therapy | Chronic End Stage Kidney DiseaseBelgium
-
University of North Carolina, Chapel HillLantheus Medical ImagingCompletedChronic Kidney Diseases | Cystic Kidney DiseaseUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States