Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients

Cinacalcet for Treatment of Persistent Secondary Hyperparathyroidism in Renal Transplant Recipients: Effect on Renal Function, Serum Calcium and Bone Histomorphometry

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.

Study Overview

• Status: Terminated
• Conditions: Secondary Hyperparathyroidism; Hypercalcemia
• Intervention / Treatment: Drug: Cinacalcet HCl

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cinacalcet Hydrochloride (HCl)	Drug: Cinacalcet HCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalization of Serum Calcium Levels	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.	Baseline to 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Renal Function	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.	Baseline to 6 Months
Changes in Bone Mineral Density	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.	Baseline to 6 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Bone Turnover Rate	Changes in bone turnover rate from baseline were to have been assessed by bone histology and histomorphometry. This was to have been conducted by an examination of bone biopsies, collected after double labeling with tetracycline compounds ~21 days prior to the procedure, to assess for bone turnover and structure. This was to have been a largely observational endpoint as no studies published at the time have described the effect of Cinacalcet HCl on bone histology.	Baseline to 6 Months

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Maria Coco, MD, MS, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2007
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: December 21, 2006
• First Submitted That Met QC Criteria: December 21, 2006
• First Posted (Estimated): December 25, 2006

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: transplant; hypercalcemia
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms; Metabolic Diseases; Neoplastic Processes; Water-Electrolyte Imbalance; Parathyroid Diseases; Calcium Metabolism Disorders; Neoplasm Metastasis; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hypercalcemia; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: 05-09-244

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes