Hypoparathyroidism
Conditions
Keywords
Hypoparathyroidism, Parathyroid Hormone, Vitamin D, Calcium Metabolism, PTH 1-34, Bone
Brief summary
This study has been important in establishing synthetic human parathyroid hormone 1-34 (PTH) as a beneficial treatment for hypoparathyroidism, superior to conventional therapy with calcium and calcitriol. Providing synthetic human parathyroid hormone 1-34 (PTH) to patients who are unresponsive to conventional therapy has enabled severe cases of hypoparathyroidism to be managed effectively with the investigational drug, PTH. The primary goals of this study are to (1) provide long-term PTH therapy to patients who do not respond to conventional therapy; (2) understand the long-term effect of therapeutic PTH replacement on kidney function and bone mineral density; (3) study and track linear growth and bone accrual in children with hypoparathyroidism. (4) determine if subjects reach a normal level of peak bone mass and if the timing of this is comparable to normal age-matched healthy controls.
Detailed description
Vitamin D and its analogs, the conventional treatment for hypoparathyroidism, are associated with chronic hypercalciuria due to their lack of calcium-retaining effect in the kidney. This side effect usually occurs even while maintaining the serum calcium in the normal range and may lead to calcium deposition in the kidney (nephrocalcinosis) and renal insufficiency. This study examines the long-term effects of subcutaneous parathyroid hormone (PTH) therapy on calcium metabolism, bone, and renal function. Our previous short-term pilot study comparing subcutaneous PTH with calcitriol demonstrated a significant decrease in urinary calcium excretion during PTH therapy. Based upon these results, we hypothesized that treatment with PTH is more physiologic and provides improved long-term metabolic control. Additionally, treatment with PTH may avoid the adverse side effects on the kidney that are associated with conventional therapy. Patients initially come to the Clinical Center for a two week inpatient evaluation. Subsequent follow-up will occur semiannually on an outpatient basis.
Interventions
DRUGSynthetic Human Parathyroid Hormone 1-34
twice daily subcutaneous injections
DRUGCalcitriol & Calcium
Twice daily oral calcitriol with 1000 mg Calcium carbonate supplementation
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
17 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: This study will include patients (ages 17-69) with biochemically confirmed hypoparathyroidism.
Exclusion criteria
Women who are pregnant will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Calcium Level | 3 years | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 2.05-2.5. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
| Urine Calcium Excretion Level | 3 years | Measurements were taken1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/24 h, normal range 1.25-6.25. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Magnesium Level | 3 years | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 0.65-1.05. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
| Serum 1,25-hydroxyvitamin D Level | 3 years | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = pg/ml. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
| Urinary Creatinine Clearance | 3 years | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = ml/min, normal range 90-125. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
| Serum Phosphorus Level | 3 years | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 0.7-1.4. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
| Serum 25-hydroxyvitamin D Level | 3 years | Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = ng/ml. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcitriol and Calcium Twice daily po calcitriol with calcium carbonate given 4 times daily | 13 |
| PTH 1-34 PTH 1-34 given as 2 subcutaneous injections daily | 14 |
| Total | 27 |
Baseline characteristics
| Characteristic | Calcitriol and Calcium | PTH 1-34 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 13 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 14 | 0 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 13 |
Outcome results
Primary
Serum Calcium Level
Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 2.05-2.5. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Serum Calcium Level | 2 mmol/liter | Standard Deviation 0.01 |
| PTH 1-34 | Serum Calcium Level | 1.92 mmol/liter | Standard Deviation 0.02 |
Primary
Urine Calcium Excretion Level
Measurements were taken1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/24 h, normal range 1.25-6.25. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Urine Calcium Excretion Level | 8.2 mmol/24 h | Standard Deviation 0.51 |
| PTH 1-34 | Urine Calcium Excretion Level | 5.8 mmol/24 h | Standard Deviation 0.27 |
Secondary
Serum 1,25-hydroxyvitamin D Level
Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = pg/ml. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Serum 1,25-hydroxyvitamin D Level | 40 pg/ml | Standard Deviation 5 |
| PTH 1-34 | Serum 1,25-hydroxyvitamin D Level | 43 pg/ml | Standard Deviation 5 |
Secondary
Serum 25-hydroxyvitamin D Level
Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = ng/ml. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Serum 25-hydroxyvitamin D Level | 31 ng/ml | Standard Deviation 5 |
| PTH 1-34 | Serum 25-hydroxyvitamin D Level | 28 ng/ml | Standard Deviation 4 |
Secondary
Serum Magnesium Level
Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 0.65-1.05. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Serum Magnesium Level | 0.75 mmol/liter | Standard Deviation 0.01 |
| PTH 1-34 | Serum Magnesium Level | 0.73 mmol/liter | Standard Deviation 0.02 |
Secondary
Serum Phosphorus Level
Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = mmol/liter, normal range 0.7-1.4. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Serum Phosphorus Level | 4.5 mmol/liter | Standard Deviation 0.05 |
| PTH 1-34 | Serum Phosphorus Level | 4.6 mmol/liter | Standard Deviation 0.08 |
Secondary
Urinary Creatinine Clearance
Measurements were taken 1 hour before the morning dose of PTH or, calcitriol and calcium; UOM = ml/min, normal range 90-125. Measurements were obtained on three successive days (three separate measures) semiannually at the NIH CC for each protocol subject. The average data are the average of these three semi-annual data points for each subject which are then averaged across all the semi-annual means for all subjects within each arm over the three years of study.
Time frame: 3 years
Population: All patients on the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Calcitriol and Calcium | Urinary Creatinine Clearance | 84 ml/min | Standard Deviation 13 |
| PTH 1-34 | Urinary Creatinine Clearance | 80 ml/min | Standard Deviation 10 |