Hypoparathyroidism
Conditions
Brief summary
Whereas much information is known about the properties of bone in primary hyperparathyroidism, a disorder of parathyroid hormone (PTH) excess, virtually nothing is known about the skeleton in hypoparathyroidism, a disorder in which PTH is absent. The purpose of this research project is to test the hypothesis that the skeleton in hypoparathyroidism is abnormal in its metabolic, densitometric, geometric, biomechanical and microarchitectural features. We will also test the hypothesis that the skeleton is dependent upon PTH for normal structure and function. Using non-invasive approaches as well as direct analysis of bone itself, the human hypoparathyroid skeleton will be thoroughly characterized. With each patient serving as his/her own control, we will determine how, to what extent, and in what ways the administration of PTH restores skeletal dynamics and structure to the hypoparathyroid skeleton. In this way, we will identify those structural and dynamic elements of the skeleton that are influenced by or dependent upon PTH. Methods to be utilized include dual energy X-ray absorptiometry, quantitative central and peripheral computed tomography, geometry and size quantification, histomorphometry by standard and microCT methods, finite element analysis, biochemical bone markers, quantitative back scattered electron imaging, and Fourier Transform Infrared Spectroscopy. This research project will extend our knowledge of the skeletal effects of PTH to its deficient range and thus complete our understanding of PTH action on bone gained by our many years of studying PTH overexpression in primary hyperparathyroidism. This investigation may also provide insight into the means by which PTH helps to restore the skeleton when it is used to treat osteoporosis.
Detailed description
A detailed description of the methods used in this study include the following: direct analysis of bone itself. skeletal dynamics and structure such as dual energy X-ray absorptiometry, quantitative central and peripheral computed tomography, geometry and size quantification, histomorphometry by standard and microCT methods, finite element analysis, biochemical bone markers, quantitative back scattered electron imaging, and Fourier Transform Infrared Spectroscopy.
Interventions
DRUGPTH
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
John P. Bilezikian
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
* Hypoparathyroidism
Exclusion criteria
* Bisphosphonate use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Requirements for Calcium Supplementation | 2 years | Serum and urinary calcium levels maintained by change in requirements for calcium supplementation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in BMD From Baseline to 24 Months by DXA | baseline versus 24 months | Bone Mineral Density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA). |
| Trabecular Width | baseline versus two years | Trabecular width was obtained from histomorphometric assessment of percutaneous iliac crest bone biopsy. Trabecular width is the thickness of individual pieces of the spongy bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed. |
| Trabecular Number | baseline versus two years | trabecular number done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Trabecular number is the number of individual pieces of the spongy bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed. |
| Cortical Porosity | baseline versus two years | Cortical porosity done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Cortical Porosity measures how many tiny holes there are in the solid bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed. |
| Mineralizing Surface | baseline versus one year | Mineralizing surface done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Mineralizing surface measures how much of bone is getting new mineral put on it. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed. |
Countries
United States
Participant flow
Recruitment details
68 subjects were enrolled from 05/12/2004 to 06/19/2014 at Columbia University Medical Center.
Pre-assignment details
The first 6 participants in the study were randomly assigned to PTH1-84 100mcg daily, 100mcg every other day, and 100mcg every three days as a pilot project to determine the correct dosing regimen.
Participants by arm
| Arm | Count |
|---|---|
| PTH1-84 participants recieved PTH1-84 in either 100mcg daily, every other day, or every three days based on investigators clinical judgement | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Off treatment early | 15 |
| Overall Study | Unrelated adverse event | 5 |
Baseline characteristics
| Characteristic | PTH1-84 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 27 |
| Region of Enrollment United States | 68 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 68 / 68 |
| serious Total, serious adverse events | 15 / 68 |
Outcome results
Primary
Requirements for Calcium Supplementation
Serum and urinary calcium levels maintained by change in requirements for calcium supplementation
Time frame: 2 years
Population: Only the first 30 participants to complete 24 months in the study were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTH1-84 | Requirements for Calcium Supplementation | Starting requirements | 3.03 grams per day of calcium supplementation | Standard Deviation 2.32 |
| PTH1-84 | Requirements for Calcium Supplementation | Requirements at month 24 | 1.66 grams per day of calcium supplementation | Standard Deviation 1.26 |
Secondary
Cortical Porosity
Cortical porosity done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Cortical Porosity measures how many tiny holes there are in the solid bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.
Time frame: baseline versus two years
Population: Only 16 subjects had paired bone biopsies obtained at baseline and after 24 months of PTH(1-84) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTH1-84 | Cortical Porosity | Baseline | 7.4 percentage of porosity | Standard Deviation 3.2 |
| PTH1-84 | Cortical Porosity | Year 2 | 9.2 percentage of porosity | Standard Deviation 2.4 |
Secondary
Mineralizing Surface
Mineralizing surface done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Mineralizing surface measures how much of bone is getting new mineral put on it. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.
Time frame: baseline versus one year
Population: Only 14 subjects had paird bone biopsies obtained at baseline and after 12 months of PTH(1-84) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTH1-84 | Mineralizing Surface | Baseline | 0.7 percentage of surface | Standard Deviation 0.6 |
| PTH1-84 | Mineralizing Surface | Year 1 | 7.1 percentage of surface | Standard Deviation 6 |
Secondary
Percent Change in BMD From Baseline to 24 Months by DXA
Bone Mineral Density (BMD) as measured by Dual-energy X-ray absorptiometry (DXA).
Time frame: baseline versus 24 months
Population: Only the first 30 participants who completed 24 months of the study were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTH1-84 | Percent Change in BMD From Baseline to 24 Months by DXA | Lumbar Spine BMD | 2.9 percentage of change to BMD | Standard Deviation 4 |
| PTH1-84 | Percent Change in BMD From Baseline to 24 Months by DXA | Femoral Neck BMD | 0.95 percentage of change to BMD | Standard Deviation 0.2 |
| PTH1-84 | Percent Change in BMD From Baseline to 24 Months by DXA | Distal 1/3 Radius BMD | -2.4 percentage of change to BMD | Standard Deviation 4 |
Secondary
Trabecular Number
trabecular number done on histomorphometric assessment of percutaneous iliac crest bone biopsy. Trabecular number is the number of individual pieces of the spongy bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.
Time frame: baseline versus two years
Population: Only 16 subjects had paired bone biopsies obtained at baseline and after 24 months of PTH(1-84) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTH1-84 | Trabecular Number | Baseline | 1.74 mm^-1 | Standard Deviation 0.34 |
| PTH1-84 | Trabecular Number | Year 2 | 2.07 mm^-1 | Standard Deviation 0.5 |
Secondary
Trabecular Width
Trabecular width was obtained from histomorphometric assessment of percutaneous iliac crest bone biopsy. Trabecular width is the thickness of individual pieces of the spongy bone section. The structure and microscopic organization of a small piece of biopsied pelvic bone was analyzed.
Time frame: baseline versus two years
Population: Only 16 subjects had paired bone biopsies obtained at baseline and after 24 months of PTH(1-84) treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PTH1-84 | Trabecular Width | Baseline | 144 micrometers | Standard Deviation 34 |
| PTH1-84 | Trabecular Width | Year 2 | 128 micrometers | Standard Deviation 34 |