Chronic Kidney Disease
Conditions
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.
Interventions
DIETARY_SUPPLEMENT1500 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.
DIETARY_SUPPLEMENTPlacebo
Placebo for calcium carbonate in same capsule form. Given 3 times per day with meals for 21 days in conjunction with a controlled diet.
Sponsors
Genzyme, a Sanofi Company
Purdue University
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Calcium Balance | 2 weeks | Calcium balance is measured by dietary calcium intake (mg/d) minus calcium excretion (mg/d) (from both urine and feces). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phosphorus Balance | 2 weeks | Phosphorus balance is measured by dietary phosphorus intake (mg/d) minus phosphorus excretion (mg/d) from both urine and feces. |
| Bone Balance From Calcium Kinetics | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcium Then Placebo Crossover order was calcium then placebo, separated by at least a 3 week washout period.
Calcium treatment was 1500 mg/d calcium as calcium carbonate given as three 500 mg calcium capsules at each of the three meals per day. Placebo was identical in shape, appearance, and administration. | 6 |
| Placebo Then Calcium Crossover order was placebo then calcium, separated by at least a 3 week washout period.
Calcium treatment was 1500 mg/d calcium as calcium carbonate given as three 500 mg calcium capsules at each of the three meals per day. Placebo was identical in shape, appearance, and administration. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo Then Calcium | Calcium Then Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 60.8 years STANDARD_DEVIATION 5.3 | 54.0 years STANDARD_DEVIATION 8.1 | 57.4 years STANDARD_DEVIATION 7.5 |
| Region of Enrollment United States | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Calcium Balance
Calcium balance is measured by dietary calcium intake (mg/d) minus calcium excretion (mg/d) (from both urine and feces).
Time frame: 2 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Calcium Balance | 61 mg/d calcium | Standard Error 60 |
| Calcium | Calcium Balance | 508 mg/d calcium | Standard Error 60 |
Secondary
Bone Balance From Calcium Kinetics
Calcium kinetics was determined by a calcium radiotracer. Bone balance is the difference between bone formation and bone resorption estimated by calcium kinetic modeling.
Time frame: 2 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Bone Balance From Calcium Kinetics | 62 mg/d calcium | Standard Error 42 |
| Calcium | Bone Balance From Calcium Kinetics | 259 mg/d calcium | Standard Error 42 |
Secondary
Phosphorus Balance
Phosphorus balance is measured by dietary phosphorus intake (mg/d) minus phosphorus excretion (mg/d) from both urine and feces.
Time frame: 2 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Phosphorus Balance | 95 mg/d phosphorus | Standard Error 29 |
| Calcium | Phosphorus Balance | 153 mg/d phosphorus | Standard Error 29 |