Secondary Hyperparathyroidism
Conditions
Keywords
hyperparathyroidism, parathyroid, vitamin D, vitamin D deficiency
Brief summary
The purpose of this study is to determine if a reduction in the enzyme 1-hydroxylase, which activates Vitamin D, is the cause of overactivity of the parathyroid glands (called secondary hyperparathyroidism - normal blood calcium and elevated parathyroid hormone) in a selected group of young patients with normal kidney function.
Detailed description
Vitamin D, an essential nutrient, is produced by the skin after sunlight shines on it. Vitamin D must then be activated by both the liver and the kidneys to perform its function of maintaining strong bones and helping to prevent heart disease, infection, diabetes and cancer. Reduced kidney activation of Vitamin D occurs with advanced age and with all kidney diseases. We have identified a small group of patients who appear to have reduced ability of the kidneys to activate vitamin D, even though they are young and do not have chronic kidney disease. In these patients, we are comparing the ability of their kidneys to activate Vitamin D to that of healthy controls. To stimulate the kidneys to activate Vitamin D, we are giving parathyroid hormone intravenously over 8 hours and collecting blood and urine at baseline, 4 and 8 hours. This type of parathyroid infusion does not cause side effects. The gene that controls this activation is also being studied (by a simple blood test) to look for abnormalities. We are now actively recruiting healthy controls for this study.
Interventions
DRUGTeriparatide
Teriparatide will be given by continuous intravenous infusion at a rate of 12 pmol/kg/hr for 8 hours to both patients and controls
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Caucasian female * Age 40-59 years * Serum creatinine \< 1.3 and estimated glomerular filtration rate (GRF) \> 60 * Serum calcium in the normal range (for U Md lab 8.6-10 mg/dl) * Parathyroid hormone in the normal range (for U Md lab 12-54 pg/ml) * Normal 25-hydroxyvitamin D level (30 ng/ml or higher) * For women of childbearing age, non-pregnant (based on negative urine pregnancy test on the morning of the teriparatide infusion)
Exclusion criteria
* Non-caucasian * Age under 40 and over 59 years * Male * Serum creatinine over 1.3 or estimated glomerular filtration rate (GFR) \< 60 * Abnormal serum calcium (for U Md lab, below 8.6 or above 10 mg/dl) * Abnormal parathyroid hormone (for U Md lab, above 65 or below 12 pg/ml) * For women of childbearing age, non-pregnant (based on urine pregnancy test on the morning of the teriparatide infusion) * History of bone radiation * History of Paget disease of bone * History of bone malignancy or metastases * History of allergy or sensitivity to Forteo
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | baseline, 4 and 8 hours after start of infusion | 1,25-D was measured at baseline, 4 and 8 hours after PTH infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With Mutations in CYP27B1 | blood samples taken at baseline and sequenced over several days | CYP27B1 gene (the gene for 25-hydroxyvitamin D-1-alpha hydroxylase) was sequenced for all in patient group and compared with published control data |
Countries
United States
Participant flow
Recruitment details
All in the patient group were recruited from the Metabolic Bone Clinic at U Md, except one, who was recruited from prior participation in the Amish Family Osteoporosis Study, recruited from 3/15/07-11/14/08
Pre-assignment details
Of 11 controls enrolled, 6 completed the study and 5 dropped out because they didn't want to do the parathyroid hormone (PTH) infusion. Of 9 patients recruited, 6 completed the study. The others were excluded after their screening labs showed that their renal function was below the inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Controls controls with normal PTH | 11 |
| Patient Group patients with secondary hyperparathyroidism | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Patient Group | Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 11 Participants | 20 Participants |
| Age, Continuous | 53.0 years STANDARD_DEVIATION 2.5 | 51.8 years STANDARD_DEVIATION 4.4 | 52.4 years STANDARD_DEVIATION 3.8 |
| Region of Enrollment United States | 9 participants | 11 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 11 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 11 | 1 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 |
Outcome results
Primary
The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours
1,25-D was measured at baseline, 4 and 8 hours after PTH infusion
Time frame: baseline, 4 and 8 hours after start of infusion
Population: The final analysis was made on participants with glomerular filtration rate (GFR) of 70 and above since \<70, 1,25-D production decreases. After study completion, it was noted that one participant in each group (patient and control) had GFR\<70 so these two participants were excluded from final analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 | The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | Baseline | 40.6 pg/ml | Standard Deviation 5.6 |
| Group 1 | The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | 4 hours | 39.8 pg/ml | Standard Deviation 6 |
| Group 1 | The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | 8 hours | 56.4 pg/ml | Standard Deviation 9.2 |
| Controls | The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | Baseline | 46.2 pg/ml | Standard Deviation 3.7 |
| Controls | The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | 4 hours | 58.8 pg/ml | Standard Deviation 6.7 |
| Controls | The Level of Activated Vitamin D (1,25-dihydroxyvitamin D) After Parathyroid Hormone Infusion at Baseline, 4 and 8 Hours | 8 hours | 105 pg/ml | Standard Deviation 2.3 |
Comparison: The null hypothesis is that there is no statistical difference between patients and controls at baselinep-value: 0.1t-test, 2 sided
Comparison: The null hypothesis is that there is no statistical difference between patients and controls at 4 hoursp-value: 0.002t-test, 2 sided
Comparison: The null hypothesis is that there is no statistical difference between patients and controls at 8 hrsp-value: 0.003t-test, 2 sided
Secondary
The Number of Patients With Mutations in CYP27B1
CYP27B1 gene (the gene for 25-hydroxyvitamin D-1-alpha hydroxylase) was sequenced for all in patient group and compared with published control data
Time frame: blood samples taken at baseline and sequenced over several days
Population: All patients were sequenced and compared to published control data. Controls were not sequenced for cost reasons
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Group 1 | The Number of Patients With Mutations in CYP27B1 | 0 participants | 5 |