Chronic Kidney Disease
Conditions
Keywords
phosphate, phosphorus, FGF-23, PTH, 1,25D
Brief summary
The purpose of this study is to learn more about how the kidneys control the blood levels of phosphorus in patients with early chronic kidney disease. The ultimate goal is to use this information to design improved treatment strategies for phosphorus-related problems for the millions of patients with chronic kidney disease.
Detailed description
Phosphorus is a mineral found in dairy products, nuts, and meat that is essential for bone health and many other important functions inside the body's cells. The kidneys are responsible for keeping the blood levels of phosphorus normal. Healthy kidneys do this by spilling excess phosphorus into the urine. In patients with chronic kidney disease, the kidneys are unable to spill an adequate amount of phosphorus so that excess phosphorus can accumulate in the walls of blood vessels leading to heart disease, their leading cause of death. A recently discovered hormone called FGF-23 helps control the blood levels of phosphorus by telling the kidney how much phosphorus to spill in the urine. The purpose of this study is to learn more about how FGF-23 helps the kidneys control the blood levels of phosphorus. The ultimate goal is to use this information to design improved treatment strategies for phosphorus-related problems for the millions of patients with chronic kidney disease.
Interventions
DIETARY_SUPPLEMENTUnrestricted Phosphorus Diet
Unrestricted diet will contain 1550 mg of phosphorus per day - 800 mg of which is dietary and 750mg of Neutraphos (3 packets/day); each packet is 250mg.
DRUGPlacebo
Lanthanum Carbonate placebo given three times a day with meals.
DRUGLanthanum Carbonate
Lanthanum carbonate 1000mg 3x/day
DIETARY_SUPPLEMENTLow Phosphorus Diet
Low phosphorus diet will consist of 800 mg of phosphorus per day.
Sponsors
Shire
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* subjects with stage 3a, 3b and 4 CKD * subjects have to be aged 18 years or older * subjects have to have normal serum phosphate levels (\< 4.6 mg/dl) * subjects have to have sufficient 25-OH Vit0amin D levels (≥ 20 ng/ml)
Exclusion criteria
* subjects with rapidly advancing renal failure who thus might develop hyperphosphatemia or end stage renal disease requiring initiation of dialysis during the study period * subjects expected to require dialysis initiation within the follow up period * subjects with hyperphosphatemia \> 4.6 mg/dL * subjects with any previous or current treatment with phosphate binders or active vitamin D (doxercalciferol or calcitriol) * subjects with malnutrition, defined as a serum albumin \< 3.0 mg/dl, in order to avoid worsening protein-malnutrition status during the restricted study period since phosphate restricted diets are also low in protein * subjects with chronic gastrointestinal diseases that could impede their absorptive ability such as Crohn's disease, ulcerative colitis and sprue * subjects with liver disease (ALT or AST \> 100 U/L) or cholestasis (direct bilirubin \> 1.0 mg/dl) because this can limit their ability to absorb fat soluble vitamins such as vitamin D * subjects with anemia, defined as a hematocrit \<27% at the screening visit * subjects wht have been hospitalization within the previous 4 weeks * subjects who are pregnant * subjects who are breastfeeding mothers * subjects with primary hypoparathyroidism * subjects with primary hyperparathyroidism * subjects with previous subtotal parathyroidectomy * subjects with previous outpatient counseling by a renal nutritionist * subjects who are unable to independently provide written informed consent - prisoners, mentally incompetent, minors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibroblast Growth Factor 23 (FGF-23) | 2 weeks | Plasma FGF-23 was measured using c-terminal FGF23 assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Urinary Phosphate | 2 weeks | from 24-hr urine collections |
Countries
United States
Participant flow
Recruitment details
16 patients completed the full study. Patients were recruited from renal clinics.
Pre-assignment details
There was no wash-out, run in or transition.
Participants by arm
| Arm | Count |
|---|---|
| Lanthanum Carbonate & Low Phosphorous Diet Lanthanum carbonate 1000mg 3x/day and low phosphorus diet of 800 mg of phosphorus per day. | 4 |
| Lanthanum Carbonate & Unrestricted Phosphorous Diet Lanthanum carbonate 1000mg 3x/day and unrestricted diet containing 1550 mg of phosphorus per day - 800 mg of which is dietary and 750mg of Neutraphos (3 packets/day); each packet is 250mg. | 4 |
| Placebo & Low Phosphorous Diet Placebo and low phosphorus diet consisting of 800 mg of phosphorus per day. | 4 |
| Placebo & Unrestricted Phosphorous Diet Placebo and unrestricted diet containing 1550 mg of phosphorus per day - 800 mg of which is dietary and 750mg of Neutraphos (3 packets/day); each packet is 250mg. | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | Lanthanum Carbonate & Low Phosphorous Diet | Lanthanum Carbonate & Unrestricted Phosphorous Diet | Placebo & Low Phosphorous Diet | Placebo & Unrestricted Phosphorous Diet | Total |
|---|---|---|---|---|---|
| 24-hr urine phosphate | 659.0 mg STANDARD_DEVIATION 269.8 | 761.8 mg STANDARD_DEVIATION 77.4 | 745.4 mg STANDARD_DEVIATION 287 | 934.6 mg STANDARD_DEVIATION 545.5 | 775.2 mg STANDARD_DEVIATION 320 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 10 Participants |
| Age Continuous | 63 years STANDARD_DEVIATION 11 | 62 years STANDARD_DEVIATION 13 | 56 years STANDARD_DEVIATION 21 | 68 years STANDARD_DEVIATION 17 | 62 years STANDARD_DEVIATION 15 |
| Fibroblast Growth Factor 23 (FGF-23) | 164.3 Ru/ml STANDARD_DEVIATION 110.9 | 263.1 Ru/ml STANDARD_DEVIATION 167.9 | 178.8 Ru/ml STANDARD_DEVIATION 97.6 | 121.8 Ru/ml STANDARD_DEVIATION 60 | 182.0 Ru/ml STANDARD_DEVIATION 116.3 |
| Region of Enrollment United States | 4 participants | 4 participants | 4 participants | 4 participants | 16 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 4 Participants | 4 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Fibroblast Growth Factor 23 (FGF-23)
Plasma FGF-23 was measured using c-terminal FGF23 assay.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate & Low Phosphorous Diet | Fibroblast Growth Factor 23 (FGF-23) | 162.695 RU/ml | Standard Error 56.170737 |
| Lanthanum Carbonate & Unrestricted Phosphorous Diet | Fibroblast Growth Factor 23 (FGF-23) | 297 RU/ml | Standard Error 77.69778 |
| Placebo & Low Phosphorous Diet | Fibroblast Growth Factor 23 (FGF-23) | 188.975 RU/ml | Standard Error 60.2020815 |
| Placebo & Unrestricted Phosphorous Diet | Fibroblast Growth Factor 23 (FGF-23) | 143.7675 RU/ml | Standard Error 37.507486 |
Secondary
24-hour Urinary Phosphate
from 24-hr urine collections
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lanthanum Carbonate & Low Phosphorous Diet | 24-hour Urinary Phosphate | 150.4 mg | Standard Error 49.3063045 |
| Lanthanum Carbonate & Unrestricted Phosphorous Diet | 24-hour Urinary Phosphate | 382.725 mg | Standard Error 7.0577825 |
| Placebo & Low Phosphorous Diet | 24-hour Urinary Phosphate | 346.8 mg | Standard Error 132.671329 |
| Placebo & Unrestricted Phosphorous Diet | 24-hour Urinary Phosphate | 830.25 mg | Standard Error 220.003449 |