Clinical trial NCT00415584: Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients
Official title: Cinacalcet for Treatment of Persistent Secondary Hyperparathyroidism in Renal Transplant Recipients: Effect on Renal Function, Serum Calcium and Bone Histomorphometry
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Secondary Hyperparathyroidism
Hypercalcemia
Keywords: hypercalcemia
transplant
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2006-12-25
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Normalization of Serum Calcium Levels
timeFrame: Baseline to 6 Months
Secondary outcomes:
measure: Changes in Renal Function
timeFrame: Baseline to 6 Months
measure: Changes in Bone Mineral Density
timeFrame: Baseline to 6 Months
Other outcomes:
measure: Changes in Bone Turnover Rate
timeFrame: Baseline to 6 Months
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Maria Coco, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: