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Current osteoporosis therapies produce a prompt increase in bone mass, followed by only modest or no further subsequent gains. This limitation, known as the "remodeling transient," reflects the "coupling" of bone resorption with formation such that interventions impacting either of these processes lead to compensatory changes of the other. For example, medications which increase bone formation promptly also stimulate bone resorption. Thus, given the need to dramatically increase bone mass in patients with osteoporosis, it is necessary to "uncouple" formation and resorption. The investigators believe this to be possible using currently existing FDA-approved therapeutic agents, by using a novel, sequential approach.
This pilot project will obtain preliminary data essential to support future work. In this study, the investigators will begin to explore the use of sequential anabolic treatment with teriparatide followed by antiresorptive therapy with raloxifene. The investigators propose that such sequential treatment will allow opening of the "anabolic window," the brief period of time following initiation of teriparatide therapy in which bone formation exceeds resorption.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Daily teriparatide (Forteo) | Active Comparator |
| |
| Monthly cycles of teriparatide followed by raloxifene | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Teriparatide | Drug | Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Markers of Skeletal Turnover (Serum CTX) | Serum CTX was measured at all study visits following the screening visit. The outcome data is an overall average and range from all time points. | These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits. |
| Serum Markers of Skeletal Turnover (Serum P1NP) | Serum P1NP was measured at all study visits following the screening visit. The outcome data is an overall average and range from all time points. | These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits. |
| Measure | Description | Time Frame |
|---|---|---|
| Average Bone Mineral Density of the Spine at Baseline, 3 Months and 6 Months | Spine BMD was measured at the baseline, three month and six month visits. The outcome data is an overall average and range from all time points. | BMD measured at the baseline, 3 month, and 6 month visits. |
| Average Bone Mineral Density of the Proximal Femur (Hip) at Baseline, 3 Months and 6 Months |
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Inclusion Criteria:
OR
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Neil Binkley, MD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin Osteoporosis Clinical Center and Research Program | Madison | Wisconsin | 53705 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Daily Teriparatide (Forteo) | Teriparatide: Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. |
| FG001 | Monthly Cycles of Teriparatide Followed by Raloxifene | Teriparatide: Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. Raloxifene: Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Daily Teriparatide (Forteo) | Teriparatide: Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. |
| BG001 | Monthly Cycles of Teriparatide Followed by Raloxifene |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Serum Markers of Skeletal Turnover (Serum CTX) | Serum CTX was measured at all study visits following the screening visit. The outcome data is an overall average and range from all time points. | Mean | Full Range | ng/mL | These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits. |
|
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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 | Daily Teriparatide (Forteo) | Teriparatide: Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Neil Binkley, MD | University of Wisconsin Osteoporosis Clinical Research Program | 608-265-6410 | uwosteoporosis@gmail.com |
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| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D019379 | Teriparatide |
| D020849 | Raloxifene Hydrochloride |
| ID | Term |
|---|---|
| D010281 | Parathyroid Hormone |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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|
| Raloxifene | Drug | Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature. |
|
|
Hip BMD was measured at the baseline, three month and six month visits. The outcome data is an overall average and range from all time points. |
| BMD measured at the baseline, 3 month, and 6 month visits. |
| Average Bone Mineral Density of the One-third Radius at Baseline, 3 Months and 6 Months | One-third radius BMD was measured at the baseline, three month and six month visits. The outcome data is an overall average and range from all time points. | BMD measured at the baseline, 3 month, and 6 month visits. |
Teriparatide: Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. Raloxifene: Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Average Bone Mineral Density of the Spine at Baseline, 3 Months and 6 Months | Spine BMD was measured at the baseline, three month and six month visits. The outcome data is an overall average and range from all time points. | Mean | Full Range | g/cm2 | BMD measured at the baseline, 3 month, and 6 month visits. |
|
|
|
| Primary | Serum Markers of Skeletal Turnover (Serum P1NP) | Serum P1NP was measured at all study visits following the screening visit. The outcome data is an overall average and range from all time points. | Mean | Full Range | mcg/L | These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits. |
|
|
|
| Secondary | Average Bone Mineral Density of the Proximal Femur (Hip) at Baseline, 3 Months and 6 Months | Hip BMD was measured at the baseline, three month and six month visits. The outcome data is an overall average and range from all time points. | Mean | Full Range | g/cm2 | BMD measured at the baseline, 3 month, and 6 month visits. |
|
|
|
| Secondary | Average Bone Mineral Density of the One-third Radius at Baseline, 3 Months and 6 Months | One-third radius BMD was measured at the baseline, three month and six month visits. The outcome data is an overall average and range from all time points. | Mean | Full Range | g/cm2 | BMD measured at the baseline, 3 month, and 6 month visits. |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Monthly Cycles of Teriparatide Followed by Raloxifene | Teriparatide: Teriparatide (TPD; Forteo) is supplied as a pre-filled syringe that dispenses 20 ug. The dose is one subcutaneous injection daily. Each pre-filled injection delivery device contains sufficient TPD for a 28-day supply of 20 mcg/day. Raloxifene: Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature. | 0 | 13 | 0 | 13 |
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| D009750 |
| Nutritional and Metabolic Diseases |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D013629 | Tamoxifen |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |