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| ID | Type | Description | Link |
|---|---|---|---|
| 1P50AR044855 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | NIH |
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Parathyroid hormone (PTH) increases bone formation and thereby improves bone density and bone strength in postmenopausal women with osteoporosis. However, prolonged PTH treatment increases bone formation less and less over time. This study will test whether increasing the daily dose of PTH sustains its ability to improve bone formation, and optional sub-studies will test several potential reasons why PTH's effects on bone formation decline over time.
In women with postmenopausal osteoporosis, PTH increases bone mineral density more than anti-resorptive agents, and its use markedly reduces the incidence of new spine and non-spine fractures. Still, PTH is not a cure for osteoporosis in many patients because PTH-stimulated bone formation declines as PTH therapy continues. Biochemical analyses suggest that bone formation and resorption peak after 6 to 9 months of daily PTH therapy and then decline progressively.
The study will last 18 months. Blood, urine, and bone density tests will occur at screening. At the start of the study, participants will be randomly assigned to one of two PTH dose regimens. Patients will go to Massachusetts General Hospital at Months 0, 3, 6, 9, 12, 15, and 18 for blood and urine collection. In addition, bone density tests by DXA will be performed at Months 0, 6, 12, and 18, and by quantitative CT scans at Months 0 and 18. Approximately 6 weeks after any change in PTH dose, each participant's blood calcium will be checked 4 to 6 hours after that day's PTH injection, and her 24-hour urine calcium excretion will also be checked.
Participants may enroll in optional substudies that will test whether reduced skeletal responses to long-term treatment with PTH are accompanied by changes in its absorption and/or destruction and whether reduced skeletal responses to long-term treatment with PTH are accompanied by parallel reductions in kidney responses to PTH.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| constant dose | Experimental | Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day. |
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| ascending dose | Experimental | Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a dose that ascends at 6 month intervals (20-30-40 mcg/day). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| synthetic hPTH 1-34 | Drug | Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34 |
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| Measure | Description | Time Frame |
|---|---|---|
| Changes in Indices of Bone Turnover | Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months*ng/ml) for the marker. | Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Bone Mineral Density (BMD) | Percent change in BMD of the spine, femur, radius, and ulna, and subtotal body, calculated as 100*[(final - month 0)/month 0] in subjects who took study therapy for at least 12 months. | baseline and 18 months (12 months in 4 subjects) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert M. Neer, MD | Massachusetts General Hospital | Principal Investigator |
| Joel S. Finkelstein, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21111078 | Result | Yu EW, Neer RM, Lee H, Wyland JJ, de la Paz AV, Davis MC, Okazaki M, Finkelstein JS. Time-dependent changes in skeletal response to teriparatide: escalating vs. constant dose teriparatide (PTH 1-34) in osteoporotic women. Bone. 2011 Apr 1;48(4):713-9. doi: 10.1016/j.bone.2010.11.012. Epub 2010 Nov 24. |
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Must satisfy inclusion and exclusion criteria.
Postmenopausal women with low bone density were recruited from 2004-2007 to participate in this study at a single academic medical center. Recruitment letters were sent to women in the Greater Boston area and the trial was also posted on clinicaltrials.gov.
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| ID | Title | Description |
|---|---|---|
| FG000 | Constant Dose PTH | Participants received constant dose synthetic hPTH 1-34 (30 mcg/day). |
| FG001 | Ascending Dose PTH | Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Constant Dose PTH | Participants received constant dose synthetic hPTH 1-34 (30 mcg/day). |
| BG001 | Ascending Dose PTH | Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Changes in Indices of Bone Turnover | Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months*ng/ml) for the marker. | Because this was a physiologic study evaluating the impact of stepwise increases in teriparatide, per protocol analysis was performed as was pre-specified in our analysis plan. Outcomes data were analyzed in women who remained on teriparatide throughout the first stepwise increase (i.e. until month 12 or later). | Posted | Mean | Standard Deviation | months*(ng/ml - baseline ng/ml) | Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18. |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Constant Dose PTH | Participants received constant dose synthetic hPTH 1-34 (30 mcg/day). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypercalcemia requiring emergency room visit | Endocrine disorders | Systematic Assessment | Patient had symptoms of weakness/nausea and was found to have hypercalcemia (calcium 14.1 mg/dL). Her PTH therapy was discontinued and she was treated with IV fluids and calcitonin, resulting in normalization of calcium to 8.5 mg/dL. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mild hypercalcemia or hypercalciuria | Endocrine disorders | Systematic Assessment | Asymptomatic |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert Neer, MD | Massachusetts General Hospital | 617-726-6723 | rneer@partners.org |
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| ID | Term |
|---|---|
| D015663 | Osteoporosis, Postmenopausal |
| D010024 | Osteoporosis |
| D001862 | Bone Resorption |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
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| Protocol Violation |
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| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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Participants received constant dose synthetic hPTH 1-34 (30 mcg/day). |
| OG001 | Ascending Dose PTH | Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day). |
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| Secondary | Change in Bone Mineral Density (BMD) | Percent change in BMD of the spine, femur, radius, and ulna, and subtotal body, calculated as 100*[(final - month 0)/month 0] in subjects who took study therapy for at least 12 months. | Final BMD was measured after 18 months of study therapy in 48 subjects and measured after 12 months of study therapy in 4 others who thereafter dropped out prematurely. Of the latter 4, 3 were in the ascending dose arm and 1 was in the constant dose arm. | Posted | Mean | Standard Deviation | percent change | baseline and 18 months (12 months in 4 subjects) |
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| 0 |
| 40 |
| 5 |
| 40 |
| EG001 | Ascending Dose PTH | Participants received ascending dose synthetic hPTH 1-34 (20-30-40 mcg/day). | 2 | 40 | 8 | 40 |
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| Diagnosed with lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment | Patient was diagnosed with lung cancer shortly after her 12 month study visit |
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| Joint pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Lower extremity edema | Blood and lymphatic system disorders | Non-systematic Assessment |
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| D009750 |
| Nutritional and Metabolic Diseases |
| Spine BMD |
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| Subtotal BMD |
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| Total hip BMD |
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