Calcium and Phosphorus Balance and Calcium Kinetics in Patients With Stage 3/4 Chronic Kidney Disease

NCT ID: NCT01161407

Last Updated: 2014-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2011-11-30

Brief Summary

The purpose of this study is to gain a better understanding of calcium absorption and metabolism in patients with Chronic Kidney Disease (CKD) using calcium balance and kinetic methods.

Detailed Description

The purpose of this study is to gain a better understanding of calcium absorption and metabolism in patients with Chronic Kidney Disease (CKD). It is important that the body get enough calcium to support many important body functions including bone health. CKD changes the calcium balance or how calcium is absorbed and excreted. Because of this, the knowledge of calcium absorption and excretion in patients with normal kidney function cannot be used to assess patients with CKD. In patients with CKD bone heath is often negatively affected due to a combination of poor calcium absorption, increased bone turnover (process where old bone is removed and new bone is formed), increased level of parathyroid hormone (PTH [ a hormone that acts to increase calcium in the blood]) and decrease in vitamin D levels. This negative effect is referred to as Chronic Kidney Disease Mineral Bone Disorder (CKD-MBD).

Treatment to correct CKD-MBD should begin early in the course of CKD. In the normal population calcium supplements are frequently used to help prevent age related bone loss. Calcium supplements can also be used in CKD patients to help bind phosphate. Maintaining correct levels of phosphate in the body is crucial in CKD. However, calcium supplements may have adverse effects by promoting calcium phosphate deposits in soft tissues like the vascular system which could increase the risk of cardiovascular disease.

Therefore this formal balance study is needed to determine if positive calcium balance occurs in patients with advanced CKD who are given calcium with meals as a phosphate binder. This study will also evaluate how the body handles phosphate.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo control for calcium carbonate, given in same capsule form as the calcium carbonate, 3 times per day with meals.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

Placebo for calcium carbonate in same capsule form. Given 3 times per day with meals for 21 days in conjunction with a controlled diet.

Calcium Carbonate (Phosphate Binder)

500 mg elemental calcium as calcium carbonate given 3 times per day with meals for a total of 1500 mg/d elemental calcium.

Group Type: ACTIVE_COMPARATOR

1500 mg/d elemental calcium as calcium carbonate

Intervention Type: DIETARY_SUPPLEMENT

500 mg elemental calcium as calcium carbonate given 3 times per day with meals for a total of 1500 mg/d elemental calcium. Given for 21 days in conjunction with a controlled diet.

Interventions

1500 mg/d elemental calcium as calcium carbonate

500 mg elemental calcium as calcium carbonate given 3 times per day with meals for a total of 1500 mg/d elemental calcium. Given for 21 days in conjunction with a controlled diet.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Placebo for calcium carbonate in same capsule form. Given 3 times per day with meals for 21 days in conjunction with a controlled diet.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. Patients with a GFR of < 45 ml/min;

2. Intact serum PTH > 37 pg/ml;

3. Age > 35 years (both genders and all races);

4. Able to perform two three-week balance studies;

5. Not on oral calcium or vitamin D other than multi vitamin, or willing to stop calcium or vitamin D for one month prior to entry in the study (day 1 of first calcium balance period);

6. Female patients must be post-menopausal (defined as last menstrual period at least 12 months prior to screening visit) or surgically sterile by hysterectomy;

7. On stable doses of diuretics, bisphosphonates, anti-epileptics (except dilantin) for at least 2 months.

Exclusion Criteria

1. Serious underlying systemic disease (including uncontrolled diabetes, lupus, hypertension, amyloid, etc);

2. Taking drugs that alter calcium and phosphate balance or homeostasis including high dose cholecalciferol or ergocalciferol (1000 U/day or 50,000U/ wk, respectively), active vitamin D metabolites, calcimimetics, PTH analogues in the last 30 days;

3. Taking drugs that the investigator feels will alter calcium balance;

4. Plan to initiate dialysis in the next six months;

5. Hypercalcemia defined as serum calcium > 10.5 mg/dl;

6. Hyperphosphatemia defined as serum phosphate >5.5mg/ml;

7. Intestinal disease that alters absorption or normal intestinal function including celiac disease, small bowel resection, bariatric surgery;

8. Smoking

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Purdue University

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Munro Peacock

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Munro Peacock, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University Hospital - Clinical Research Center

Indianapolis, Indiana, United States

Countries

United States

References

Francis RM, Peacock M, Barkworth SA. Renal impairment and its effects on calcium metabolism in elderly women. Age Ageing. 1984 Jan;13(1):14-20. doi: 10.1093/ageing/13.1.14.

Reference Type: BACKGROUND

PMID: 6422710 (View on PubMed)

Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007 Jan;71(1):31-8. doi: 10.1038/sj.ki.5002009. Epub 2006 Nov 8.

Reference Type: BACKGROUND

PMID: 17091124 (View on PubMed)

Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):520-8. doi: 10.1681/ASN.2004070602. Epub 2004 Dec 22.

Reference Type: BACKGROUND

PMID: 15615819 (View on PubMed)

Jackman LA, Millane SS, Martin BR, Wood OB, McCabe GP, Peacock M, Weaver CM. Calcium retention in relation to calcium intake and postmenarcheal age in adolescent females. Am J Clin Nutr. 1997 Aug;66(2):327-333. doi: 10.1093/ajcn/66.2.327.

Reference Type: BACKGROUND

PMID: 9250111 (View on PubMed)

Coburn JW, Hartenbower DL, Massry SG. Intestinal absorption of calcium and the effect of renal insufficiency. Kidney Int. 1973 Aug;4(2):96-104. doi: 10.1038/ki.1973.88. No abstract available.

Reference Type: BACKGROUND

PMID: 4275344 (View on PubMed)

Peacock M, Aaron JE, Walker GS, Davison AM. Bone disease and hyperparathyroidism in chronic renal failure: the effect of 1alpha-hydroxyvitamin D3. Clin Endocrinol (Oxf). 1977 Dec;7 Suppl:73s-81s. doi: 10.1111/j.1365-2265.1977.tb03365.x. No abstract available.

Reference Type: BACKGROUND

PMID: 606428 (View on PubMed)

Weaver CM, Martin BR, Plawecki KL, Peacock M, Wood OB, Smith DL, Wastney ME. Differences in calcium metabolism between adolescent and adult females. Am J Clin Nutr. 1995 Mar;61(3):577-81. doi: 10.1093/ajcn/61.3.577.

Reference Type: BACKGROUND

PMID: 7872222 (View on PubMed)

Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.

Reference Type: DERIVED

PMID: 40576086 (View on PubMed)

Stremke ER, McCabe LD, McCabe GP, Martin BR, Moe SM, Weaver CM, Peacock M, Hill Gallant KM. Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study. Clin J Am Soc Nephrol. 2018 Jul 6;13(7):1002-1012. doi: 10.2215/CJN.00390118. Epub 2018 Jun 19.

Reference Type: DERIVED

PMID: 29921736 (View on PubMed)

Hill KM, Martin BR, Wastney ME, McCabe GP, Moe SM, Weaver CM, Peacock M. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int. 2013 May;83(5):959-66. doi: 10.1038/ki.2012.403. Epub 2012 Dec 19.

Reference Type: DERIVED

PMID: 23254903 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/23254903

Pubmed entry of publication from this study.

Other Identifiers

Genzyme - 0907-07

Identifier Type: -

Identifier Source: org_study_id