Fosrenol and Phosphorus Balance - Lanthanum Carbonate
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 30 - 65 |
| Updated: | 5/10/2017 |
| Start Date: | March 2012 |
| End Date: | May 2017 |
Effect of Lanthanum Carbonate (Fosrenol) on Fecal Phosphorus Excretion and Phosphorus Balance
Positive phosphorus balance and hyperphosphatemia (increased serum phosphorus levels) are
very common complications of people with advanced chronic kidney disease (i.e., stage 5
CKD), including chronic dialysis patients, and are associated with severe morbidity and
increased mortality. Despite attempts to control serum phosphorus with dietary phosphorus
restriction and the use of medicines that bind phosphorus in the gastrointestinal tract so
that the phosphorus cannot be absorbed into the body( also called phosphate binders),
chronic dialysis patients frequently remain hyperphosphatemic, particularly at the time when
they commence each of their regular dialysis treatments.
Fosrenol (lanthanum carbonate, manufactured by Shire Pharmaceuticals) is a gastrointestinal
phosphate binder that appears to have the advantages of being safe, well tolerated and
effective at binding phosphate. There are limited data on the magnitude of binding of
phosphorus by Fosrenol in the human gastrointestinal tract of patients with chronic kidney
disease.
The specific aims for this proposal are as follows:
1. To quantify, under precisely controlled metabolic balance conditions, the increase in
fecal excretion of dietary phosphorus that occurs when patients undergoing chronic
peritoneal dialysis (CPD) ingest Fosrenol (lanthanum carbonate).
2. To examine a dose response relationship between Fosrenol treatment and fecal phosphorus
excretion. The investigators will examine in CPD patients ingesting a constant
phosphorus intake, how much additional phosphorus is excreted in the feces at three
different dose levels of Fosrenol, 1.5, 3.0, and 4.5 g/day.
3. To examine how increased fecal phosphorus losses and more negative phosphorus balance
caused by Fosrenol intake affects serum phosphorus and such hormonal regulators of
phosphorus metabolism as serum parathyroid hormone (PTH), fibroblast growth factor-23,
25-hydroxycholecalciferol (25(OH)D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and
fetuin-A.
4. To assess whether there is any effect of Fosrenol and increased intestinal phosphate
binding on protein-nitrogen balance.
very common complications of people with advanced chronic kidney disease (i.e., stage 5
CKD), including chronic dialysis patients, and are associated with severe morbidity and
increased mortality. Despite attempts to control serum phosphorus with dietary phosphorus
restriction and the use of medicines that bind phosphorus in the gastrointestinal tract so
that the phosphorus cannot be absorbed into the body( also called phosphate binders),
chronic dialysis patients frequently remain hyperphosphatemic, particularly at the time when
they commence each of their regular dialysis treatments.
Fosrenol (lanthanum carbonate, manufactured by Shire Pharmaceuticals) is a gastrointestinal
phosphate binder that appears to have the advantages of being safe, well tolerated and
effective at binding phosphate. There are limited data on the magnitude of binding of
phosphorus by Fosrenol in the human gastrointestinal tract of patients with chronic kidney
disease.
The specific aims for this proposal are as follows:
1. To quantify, under precisely controlled metabolic balance conditions, the increase in
fecal excretion of dietary phosphorus that occurs when patients undergoing chronic
peritoneal dialysis (CPD) ingest Fosrenol (lanthanum carbonate).
2. To examine a dose response relationship between Fosrenol treatment and fecal phosphorus
excretion. The investigators will examine in CPD patients ingesting a constant
phosphorus intake, how much additional phosphorus is excreted in the feces at three
different dose levels of Fosrenol, 1.5, 3.0, and 4.5 g/day.
3. To examine how increased fecal phosphorus losses and more negative phosphorus balance
caused by Fosrenol intake affects serum phosphorus and such hormonal regulators of
phosphorus metabolism as serum parathyroid hormone (PTH), fibroblast growth factor-23,
25-hydroxycholecalciferol (25(OH)D3), 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and
fetuin-A.
4. To assess whether there is any effect of Fosrenol and increased intestinal phosphate
binding on protein-nitrogen balance.
Seven clinically stable patients who have been undergoing CPD for at least six months will
be admitted to the General Clinical and Research Center (GCRC) at Harbor-UCLA Medical Center
for 46 days. During this time they will be fed, under strict metabolic balance study
conditions, a constant energy and protein intake designed to meet their previously
ascertained nutritional needs. Their dietary intakes of phosphorus, calcium and magnesium
will be maintained constant throughout the 46 days of study at 1100 mg/day, 1000 mg/day and
200 mg/day, respectively. Patients will be treated throughout the study with a constant
peritoneal dialysis regimen that consists of either continuous ambulatory peritoneal
dialysis with four dialysate exchanges daily or automated peritoneal dialysis in which they
will each receive about four dialysate exchanges per night; and possibly day-time dialysate
exchanges. The number and volume of dialysate exchanges and the dialysate glucose
concentration may vary among patients according to their metabolic and clinical needs, but
will be constant for each patient. Patients will adhere to standard metabolic balance
protocols as the investigators have conducted during our many previous metabolic balance
studies. These protocols will include participating in prescribed daily exercise regimens
that are designed to maintain the patients' physical activity at their prestudy, outpatient
levels.
All patients will first undergo a 10 day Baseline period for metabolic equilibration during
which time they will not receive any phosphate binder. They will then receive three periods
of Fosrenol treatment with three different dose levels for 12 days each. During each of
three periods, the patients will receive, in random order, one or two Fosrenol tablets that
will provide 500, 1000, or 1500 mg with each of the three meals that they will be fed each
day. Thus these CPD patients will receive in random order 1500, 3000 and 4500 mg/day of
Fosrenol each prescribed for one 12 day period.
Outcome Measurements. All urine, collected in 24 hour urine specimens, and all feces
excreted, collected over four day periods, will be obtained continuously. Every 4 days a
duplicate 24 hour diet will be prepared for chemical analyses. The above specimens will be
analyzed for phosphorus, calcium and nitrogen by spectrographic, atomic absorption
spectroscopic and Kjeldahl analyses, respectively. Serum phosphorus, calcium, parathyroid
hormone (PTH), fibroblast growth factor-23, 25-hydroxycholecalciferol (25(OH)D3),
1,25-dihydroxycholecalciferol (1,25(OH)2D3), fetuin-A, urea and creatinine will be measured
in the fasting state at the beginning of the 40 day balance period and every 5 days.
Anthropometry and other standard measurements that are routinely conducted during metabolic
balance procedures will also be performed.
be admitted to the General Clinical and Research Center (GCRC) at Harbor-UCLA Medical Center
for 46 days. During this time they will be fed, under strict metabolic balance study
conditions, a constant energy and protein intake designed to meet their previously
ascertained nutritional needs. Their dietary intakes of phosphorus, calcium and magnesium
will be maintained constant throughout the 46 days of study at 1100 mg/day, 1000 mg/day and
200 mg/day, respectively. Patients will be treated throughout the study with a constant
peritoneal dialysis regimen that consists of either continuous ambulatory peritoneal
dialysis with four dialysate exchanges daily or automated peritoneal dialysis in which they
will each receive about four dialysate exchanges per night; and possibly day-time dialysate
exchanges. The number and volume of dialysate exchanges and the dialysate glucose
concentration may vary among patients according to their metabolic and clinical needs, but
will be constant for each patient. Patients will adhere to standard metabolic balance
protocols as the investigators have conducted during our many previous metabolic balance
studies. These protocols will include participating in prescribed daily exercise regimens
that are designed to maintain the patients' physical activity at their prestudy, outpatient
levels.
All patients will first undergo a 10 day Baseline period for metabolic equilibration during
which time they will not receive any phosphate binder. They will then receive three periods
of Fosrenol treatment with three different dose levels for 12 days each. During each of
three periods, the patients will receive, in random order, one or two Fosrenol tablets that
will provide 500, 1000, or 1500 mg with each of the three meals that they will be fed each
day. Thus these CPD patients will receive in random order 1500, 3000 and 4500 mg/day of
Fosrenol each prescribed for one 12 day period.
Outcome Measurements. All urine, collected in 24 hour urine specimens, and all feces
excreted, collected over four day periods, will be obtained continuously. Every 4 days a
duplicate 24 hour diet will be prepared for chemical analyses. The above specimens will be
analyzed for phosphorus, calcium and nitrogen by spectrographic, atomic absorption
spectroscopic and Kjeldahl analyses, respectively. Serum phosphorus, calcium, parathyroid
hormone (PTH), fibroblast growth factor-23, 25-hydroxycholecalciferol (25(OH)D3),
1,25-dihydroxycholecalciferol (1,25(OH)2D3), fetuin-A, urea and creatinine will be measured
in the fasting state at the beginning of the 40 day balance period and every 5 days.
Anthropometry and other standard measurements that are routinely conducted during metabolic
balance procedures will also be performed.
Inclusion Criteria:
- Chronic peritoneal dialysis treatment(CPD) for at least the previous six months,
Clinically stable,
- Ages 30 to 65 years old,
- Both genders,
- Any racial or ethnic background,
- Evidence that the subject is capable of giving informed consent and of adhering to
the study protocol.
Exclusion Criteria:
- No inflammatory or catabolic illnesses.
- No hospitalizations within the previous three months except for vascular access
revision,
- No severe heart, liver or lung failure,
- No cancer, other than basal cell carcinoma, systemic infections, vasculitis or other
rheumatological diseases.
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