Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients

Phase 1

Terminated

Conditions: Hypercalcemia
Secondary Hyperparathyroidism

Interventions: Drug: Cinacalcet HCl

Registration Number: NCT00415584

Lead Sponsor: Montefiore Medical Center

Brief Summary: Secondary hyperparathyroidism can persist following successful renal transplantation and can cause high blood calcium, kidney dysfunction or failure and excessive bone loss among other problems. If the condition does not resolve, surgery is frequently required to remove the parathyroid glands, with all the inherent risks of surgery. Cinacalcet, a medicine used to treat secondary hyperparathyroidism in patients with kidney disease, may be effective in treating this condition in renal transplant recipients. The investigator team will study the effect of cinacalcet on calcium, bone and renal function in a 6 month treatment protocol.

Detailed Description: Secondary Hyperparathyroidism in the renal transplant recipient can cause abnormal bone and mineral metabolism, resulting in hypercalcemia that is detrimental to renal function, causing renal dysfunction and calcinosis. These patients often require parathyroidectomy to correct the hypercalcemia. Surgery is not without significant risk to the patient. Risks include vocal cord paralysis, protracted hypocalcemia, cardiac arrhythmias, muscle cramps. In addition, parathyroidectomy has been associated with subsequent renal impairment.

Cinacalcet is a calcimimetic agent that is very effective in the treatment of secondary hyperparathyroidism in patients with renal failure as well as in hypercalcemia of parathyroid cancer. There have been reports of short term Cinacalcet use in renal transplant recipients. Serum calcium was improved in these patients.

However, little is known about the effect of cinacalcet on bone activity and turnover. It is not known whether Cinacalcet causes low turnover bone activity with adynamic bone disease. It is known that low turnover bone disease in renal patients can by itself cause hypercalcemia as the bone becomes static and unable to respond to everyday calcium loads.

Studies have shown that adynamic bone can develop in renal transplant recipients under a variety of conditions. It is not known what effect, if any, cinacalcet has on the bone activity of renal transplant recipients with persistent secondary hyperparathyroidism.

The purpose of the study is to determine the effect of Cinacalcet on serum calcium, renal function and bone histology in renal transplant recipients.

This is a prospective, open-label study. Protocol procedures will include baseline and 6 month measurements of bone mineral density, bone biochemical parameters, glomerular filtration rate, anterior iliac crest bone biopsy. Subjects will start cinacalcet after the first biopsy. The medication will be titrated to normalize serum calcium. Medication will be supplied by the study. Serum electrolytes will be monitored as indicated.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

Inclusion Criteria

Renal transplant recipient at least 3 months post transplant
Hypercalcemic, with serum calcium > 10.5 milliequivalents per liter (mEq/L)
Persistent hyperparathyroidism, with inappropriately elevated parathyroid hormone (PTH)

Exclusion Criteria

Allergic to Cinacalcet HCl, tetracycline
Pregnant
On medication that utilizes same liver system as Cinacalcet HCl

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cinacalcet Hydrochloride (HCl)	Cinacalcet HCl	-

Primary Outcome Measures

Name	Time	Method
Normalization of Serum Calcium Levels	Baseline to 6 Months	Serum calcium was to have been assessed by drawing venous blood samples for serum analysis. Normal blood calcium levels for adults range from approximately 8.5 to 10.4 mg/dL, but vary depending on laboratory reference ranges. Changes in serum calcium levels from baseline following treatment with Cinacalcet HCl were to have been summarized and evaluated using paired t-tests.

Secondary Outcome Measures

Name	Time	Method
Changes in Renal Function	Baseline to 6 Months	Change in renal function from baseline was to have been assessed at 6 months based on a measurement of Glomerular Filtration Rate (GFR). Normal GFR ranges vary based on age, sex, and body size but are typically \> 90 mL/min/1.73 m\^2 for healthy individuals. Changes in renal glomerular filtration rate from baseline following treatment with Cinacalcet HCl were to have been summarized and evaluated using paired t-tests.
Changes in Bone Mineral Density	Baseline to 6 Months	Changes in bone mineral density was assessed using central dual energy x-ray absorptiometry (DXA or DEXA). DXA uses radiation to measure how much calcium and other minerals are in a specific area of the bone. For this study, changes in bone mineral density of the left hip, lumbar spine, and left forearm (vs baseline) have been summarized and reported as a percentage change from baseline. Statistical t-tests were not conducted due to limited sample size.