Low Phosphate Diets in Patients With Early Stages of Chronic Kidney Disease

• ClinicalTrials.gov Identifier: NCT00438932
• Recruitment Status: Completed
• First Posted: February 22, 2007
• Results First Posted: September 27, 2011
• Last Update Posted: September 27, 2011
• Sponsor: Massachusetts General Hospital
• Collaborator: Shire
• Information provided by (Responsible Party): Myles S. Wolf, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease	Drug: Lanthanum Carbonate; Dietary Supplement: Low Phosphorus Diet; Dietary Supplement: Unrestricted Phosphorus Diet; Drug: Placebo	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Reduced Phosphate Intake in "Normo-Phosphatemic" Chronic Kidney Disease Patients
• Study Start Date: January 2007
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Lanthanum Carbonate and Low Phosphorus Diet; 25% of subjects will receive binders plus a phosphate restricted diet.	Drug: Lanthanum Carbonate; Lanthanum carbonate 1000mg 3x/day; Dietary Supplement: Low Phosphorus Diet; Low phosphorus diet will consist of 800 mg of phosphorus per day.
Active Comparator: Lanthanum Carbonate and Unrestricted Phosphorus Diet; 25% binders + unrestricted phosphate diet.	Drug: Lanthanum Carbonate; Lanthanum carbonate 1000mg 3x/day; Dietary Supplement: Unrestricted 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.; Other Name: Neutraphos
Active Comparator: Placebo and Low Phosphorus Diet; 25% placebo + phosphate restricted diet.	Dietary Supplement: Low Phosphorus Diet; Low phosphorus diet will consist of 800 mg of phosphorus per day.; Drug: Placebo; Lanthanum Carbonate placebo given three times a day with meals.
Active Comparator: Placebo and Unrestricted Phosphorus Diet; 25% placebo + unrestricted phosphate diet.	Dietary Supplement: Unrestricted 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.; Other Name: Neutraphos; Drug: Placebo; Lanthanum Carbonate placebo given three times a day with meals.

Outcome Measures

Primary Outcome Measures :

1. Fibroblast Growth Factor 23 (FGF-23) [ Time Frame: 2 weeks ]
   Plasma FGF-23 was measured using c-terminal FGF23 assay.

Secondary Outcome Measures :

1. 24-hour Urinary Phosphate [ Time Frame: 2 weeks ]
   from 24-hr urine collections

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Shire

Investigators

• Principal Investigator: Myles Wolf, MD, MMSc; Univesity of Miami Miller School of Medicine
• Principal Investigator: Harald Jueppner, MD; Massachusetts General Hospital

More Information

Publications of Results:

Isakova T, Gutiérrez OM, Smith K, Epstein M, Keating LK, Jüppner H, Wolf M. Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease. Nephrol Dial Transplant. 2011 Feb;26(2):584-91. doi: 10.1093/ndt/gfq419. Epub 2010 Jul 14.

• Responsible Party: Myles S. Wolf, Associate Professor, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00438932
• Other Study ID Numbers: 2005P000486
• First Posted: February 22, 2007
• Results First Posted: September 27, 2011
• Last Update Posted: September 27, 2011
• Last Verified: September 2011

Keywords provided by Myles S. Wolf, Massachusetts General Hospital:

phosphate, phosphorus, FGF-23, PTH, 1,25D

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Renal Insufficiency