Fosrenol and Phosphorus Balance - Lanthanum Carbonate

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Los Angeles Biomedical Research Institute
Sponsor:
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier:
NCT01581996
First received: April 9, 2012
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

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.

Condition Intervention
Chronic Kidney Failure
End-stage Renal Disease
Disorders Associated With Peritoneal Dialysis
Drug: lanthanum carbonate

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Lanthanum Carbonate (Fosrenol) on Fecal Phosphorus Excretion and Phosphorus Balance

Resource links provided by NLM:


Further study details as provided by Los Angeles Biomedical Research Institute:

Primary Outcome Measures:
  • Fecal Phosphorus and Body Phosphorus Balance [ Time Frame: Two years ] [ Designated as safety issue: No ]
    Dose response relationship between lanthanum carbonate(Fosrenol) intake and fecal phosphorus excretion and body phosphorus balance. Specifically, the phosphorus content of feces, urine, expended dialysate, diet and any vomitus or rejected food will be measured.


Secondary Outcome Measures:
  • Fecal Calcium and Nitrogen and Body Calcium and Nitrogen Balance [ Time Frame: Two years ] [ Designated as safety issue: No ]
    Fecal calcium and nitrogen and calcium and nitrogen balance in chronic peritoneal dialysis patients eating lanthanum carbonate (Fosrenol) intake. Effect of ingestion of Fosrenol on serum phosphorus and 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.

  • Protein-nitrogen balance [ Time Frame: Two years ] [ Designated as safety issue: No ]
    Lanthanum carbonate (Fosrenol) and increased intestinal phosphate binding on protein-nitrogen balance.

  • Gastrointestinal symptoms [ Time Frame: Two years ] [ Designated as safety issue: No ]
    Gastrointestinal symptoms, particularly for anorexia, nausea vomiting, abdominal pain, distention, flatulence, constipation, diarrhea.


Estimated Enrollment: 7
Study Start Date: March 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lanthanum carbonate treatment
One Treatment arm. All patients will receive the following doses of lanthanum carbonate(Fosrenol)for 10-12 days each: 0 mg, 500 mg tid, 1000 mg tid and 1500 mg tid.
Drug: lanthanum carbonate
All patients will receive the following doses of lanthanum carbonate in random order for 10 -12 days each. O mg, 500 mg tid, 1000 mg tid, 1500 mg tid.
Other Name: Fosrenol

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01581996

Contacts
Contact: Joel D. Kopple, M.D. 310-222-3891 Jkopple@labiomed.org

Locations
United States, California
Harbor-UCLA Medical Center Recruiting
Torrance, California, United States, 90509
Principal Investigator: Joel D. Kopple, M.D.         
Sponsors and Collaborators
Los Angeles Biomedical Research Institute
Investigators
Principal Investigator: Joel D. Kopple, M.D. Los Angeles Biomedical Research Institute
  More Information

No publications provided

Responsible Party: Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT01581996     History of Changes
Other Study ID Numbers: 20266-01
Study First Received: April 9, 2012
Last Updated: October 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Los Angeles Biomedical Research Institute:
Chronic renal failure
End-stage renal disease
Chronic peritoneal dialysis
Serum phosphorus
Hyperphosphatemia
Phosphate binders
Phosphate

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic

ClinicalTrials.gov processed this record on October 16, 2014