Hypercalcemia, Secondary Hyperparathyroidism
Conditions
Keywords
hypercalcemia, transplant
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.
Interventions
DRUGCinacalcet HCl
Sponsors
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Bone Turnover Rate | Baseline to 6 Months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cinacalcet HCl Cinacalcet HCl | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cinacalcet HCl |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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.
Time frame: Baseline to 6 Months
Population: Venous blood samples were not collected and processed and, as such, serum calcium data was not available for this study.
Secondary
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.
Time frame: Baseline to 6 Months
Population: Bone mineral density scans taken yielded inconsistent/unreliable results and, as such, powered statistical testing was not conducted. Left forearm scans were only obtained for 3 of the 4 patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cinacalcet HCl | Changes in Bone Mineral Density | Left Hip | -6.9 percentage change from basline |
| Cinacalcet HCl | Changes in Bone Mineral Density | Spine - Lumbar | -12.9 percentage change from basline |
| Cinacalcet HCl | Changes in Bone Mineral Density | Left Forearm | -1.2 percentage change from basline |
Secondary
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.
Time frame: Baseline to 6 Months
Population: GFR data was not collected for this study and changes in renal function were not able to be assessed.
Other Pre-specified
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.
Time frame: Baseline to 6 Months
Population: Crest bone biopsy samples were collected from the four patients; however, results could not be generalized.