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

• ClinicalTrials.gov Identifier: NCT01161407
• Recruitment Status: Completed
• First Posted: July 13, 2010
• Results First Posted: July 31, 2013
• Last Update Posted: July 29, 2014
• Sponsor: Indiana University
• Collaborators: Genzyme, a Sanofi Company; Purdue University
• Information provided by (Responsible Party): Munro Peacock, Indiana University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease	Dietary Supplement: 1500 mg/d elemental calcium as calcium carbonate; Dietary Supplement: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Calcium and Phosphorus Balance and Calcium Kinetics in Patients With Stage 3/4 Chronic Kidney Disease
• Study Start Date: June 2010
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo control for calcium carbonate, given in same capsule form as the calcium carbonate, 3 times per day with meals.	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.
Active Comparator: 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.	Dietary Supplement: 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.

Outcome Measures

Primary Outcome Measures :

1. Calcium Balance [ Time Frame: 2 weeks ]
   Calcium balance is measured by dietary calcium intake (mg/d) minus calcium excretion (mg/d) (from both urine and feces).

Secondary Outcome Measures :

1. Phosphorus Balance [ Time Frame: 2 weeks ]
   Phosphorus balance is measured by dietary phosphorus intake (mg/d) minus phosphorus excretion (mg/d) from both urine and feces.
2. "Bone Balance" From Calcium Kinetics [ Time Frame: 2 weeks ]
   Calcium kinetics was determined by a calcium radiotracer. Bone balance is the difference between bone formation and bone resorption estimated by calcium kinetic modeling.

Eligibility Criteria

• Ages Eligible for Study: 35 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Indiana

Indiana University Hospital - Clinical Research Center

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

Genzyme, a Sanofi Company

Purdue University

Investigators

• Principal Investigator: Munro Peacock, MD; Indiana University

More Information

Additional Information:

Pubmed entry of publication from this study. 

Publications:

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.

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. Erratum In: Kidney Int. 2009 Jun;75(11):1237. Kidney Int. 2009 Jun 1;75(11):1237.

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.

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.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Munro Peacock, Professor, Indiana University
• ClinicalTrials.gov Identifier: NCT01161407
• Other Study ID Numbers: Genzyme - 0907-07
• First Posted: July 13, 2010
• Results First Posted: July 31, 2013
• Last Update Posted: July 29, 2014
• Last Verified: July 2014

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Calcium Carbonate; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Antacids; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents