OsteoporosisPhase 4NCT01166958
Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?
A Phase 4 study testing Teriparatide and Raloxifene in people with Osteoporosis, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 60 to 89 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoporosis
- What is being tested?
- Teriparatide and Raloxifene
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Nov 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 89 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Generally healthy, community-dwelling ambulatory post-menopausal women.
- Able and willing to sign informed consent.
- Age 60 to 89.
- Have osteoporosis defined as follows:
- BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of -2.5 to -4.0; note: the lumbar spine must include two vertebrae that are evaluable by DXA in the opinion of the investigator.
- OR
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- BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of -1.5 or lower and either an atraumatic (in the opinion of the investigator) nonvertebral fracture; [note: nonvertebral fracture sites include the wrist, hip, pelvis, ribs, humerus, clavicle, femur, tibia and fibula] or a minimum of two mild or one moderate or severe atraumatic vertebral fractures (defined using the Genant visual semi-quantitative scale).
- Baseline serum 25(OH)D concentration > 20 ng/ml and < 60 ng/ml.
- Able and willing to receive daily subcutaneous injections using a Forteo® pen.
Who cannot join
- History of exposure to external beam or implant radiation therapy involving the skeleton.
- Paget's disease or unexplained elevations of alkaline phosphatase.
- Any history of venous thrombosis including deep vein thrombosis, pulmonary embolism, retinal vein thrombosis and superficial phlebitis.
- Documented atherosclerotic vascular disease, including but not limited to prior myocardial infarction, angina, atrial fibrillation, stroke and TIA.
- Marked hypertriglyceridemia (>500 mg/dl).
- History of prior treatment with estrogen resulting in hypertriglyceridemia (> 500 mg/dl).
Show all 29Show fewer
- Serum calcium, alkaline phosphatase, PTH or TSH outside the normal reference range.
- History of nephrolithiasis or urolithiasis within 10 years prior to enrollment; those with a history of nephro- or urolithiasis must have an appropriate radiology study (e.g., IVP or KUB) within six months documenting absence of stones.
- Baseline 24-hour urine calcium > 250 mg.
- Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis.
- History of any form of cancer except adequately treated squamous cell or basal cell skin carcinoma.
- Use of active vitamin D analogs or high dose vitamin D (≥50,000 IU weekly) in the last year.
- Active or suspected diseases (within 1 year prior to enrollment) that affect bone metabolism, e.g., renal osteodystrophy, hyperthyroidism, osteomalacia, hyperparathyroidism.
- Known allergy, hypersensitivity, contraindication or intolerance to teriparatide or raloxifene.
- History of vaginal bleeding within the past year.
- Renal failure or substantial hepatic impairment. Note "renal failure" is defined as a calculated creatinine clearance (using the Cockroft-Gault formula) of ≤ 35 ml/minute.
- Severe disease, e.g., cardiac, hepatic, pulmonary, etc., which may limit ability to complete this study. Specifically, significantly impaired hepatic function (ALT or GGT 3x the upper limit of normal.
- Known malabsorption syndromes, e.g., celiac disease, active inflammatory bowel disease, gastric bypass, etc.
- Use of anion exchange resins (e.g., cholestyramine) in the past month.
- Current use of warfarin (coumadin).
- Current use of highly protein-bound drugs including diazepam, diazoxide and lidocaine.
- Current use of digoxin.
- Any prior use of bisphosphonates, denosumab, strontium, fluoride, teriparatide or parathyroid hormone.
- Prior use of estrogen, raloxifene, calcitonin or testosterone will be allowed if discontinued more than six months previously. Low dose intra-vaginal estrogens (0.3 mg or less of conjugated equine estrogen or equivalent) may be continued throughout the study.
- Treatment with glucocorticoids in doses ≥ 5 mg prednisone daily for > 30 days in the prior year.
- Treatment with other drugs known to affect bone metabolism, e.g., anticonvulsants except benzodiazepines or gabapentin, within the prior year. Note: oral calcium supplementation, vitamin D supplementation or diuretic use that has been stable for six months are allowed).
- Treatment within the last 30 days with any drug that has not received regulatory approval.
- Metal in spine precluding spine QCT.
- Any condition that may interfere with evaluation of at least two lumbar vertebrae determined on VFA performed at time of screening. Examples include confluent aortic calcification, severe osteoarthritis, spinal fusion and lumbar spine fractures.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Osteoporosis Clinical Center and Research Program
Madison, Wisconsin, 53705
About this study
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.
- Conditions
- Osteoporosis
- Being tested
- Teriparatide, Raloxifene
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TeriparatideDrug
Also called Forteo
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.
RaloxifeneDrug
Also called Evista
Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature.
| Study group | Role | What they receive |
|---|---|---|
| Daily teriparatide (Forteo) | Active comparator | Not described Receives: Drug: Teriparatide |
| Monthly cycles of teriparatide followed by raloxifene | Active comparator | Not described Receives: Drug: Teriparatide; Drug: Raloxifene |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits.
Secondary outcomes (3)
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.
Measured: 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
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.
Measured: 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.
Measured: BMD measured at the baseline, 3 month, and 6 month visits.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2010 (estimated)
- Study startSep 2010
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Neil Binkley, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01166958
- Sponsor's protocol ID
- H-2010-0064
- Status last verified
- Sep 2014
- First submitted
- 15 Jul 2010
- Last updated
- 22 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?
- ClinicalTrials.gov ID
- NCT01166958
- Acronym / sponsor ID
- H-2010-0064
- Conditions
- Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 21 Jul 2010 (estimated)
- Results
- Posted 22 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daily teriparatide (Forteo) | Active comparator | Drug: Teriparatide |
| Monthly cycles of teriparatide followed by raloxifene | Active comparator | Drug: Teriparatide, Drug: Raloxifene |
Who may qualify
- Ages
- 60 to 89 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Generally healthy, community-dwelling ambulatory post-menopausal women.
- Able and willing to sign informed consent.
- Age 60 to 89.
- Have osteoporosis defined as follows:
- BMD T-score of the lumbar spine, femur neck, total proximal femur or .3 radius of -2.5 to -4.0; note: the lumbar spine must include two vertebrae that are evaluable by DXA in the opinion of the investigator.
Key exclusion criteria (29 listed)
- History of exposure to external beam or implant radiation therapy involving the skeleton.
- Paget's disease or unexplained elevations of alkaline phosphatase.
- Any history of venous thrombosis including deep vein thrombosis, pulmonary embolism, retinal vein thrombosis and superficial phlebitis.
- Documented atherosclerotic vascular disease, including but not limited to prior myocardial infarction, angina, atrial fibrillation, stroke and TIA.
- Marked hypertriglyceridemia (>500 mg/dl).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TeriparatideAlso: ForteoTeriparatide (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. | Drug | Daily teriparatide (Forteo), Monthly cycles of teriparatide followed by raloxifene |
| RaloxifeneAlso: EvistaRaloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature. | Drug | Monthly cycles of teriparatide followed by raloxifene |
Primary outcome
Serum Markers of Skeletal Turnover (Serum CTX)
Time frame: These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits.
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.
Serum Markers of Skeletal Turnover (Serum P1NP)
Time frame: These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits.
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.
3 secondary outcomes
Average Bone Mineral Density of the Spine at Baseline, 3 Months and 6 Months
Time frame: 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
Time frame: 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
Time frame: BMD measured at the baseline, 3 month, and 6 month visits.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neil Binkley, MD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Teriparatide and Raloxifene in people with Osteoporosis, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Markers of Skeletal Turnover (Serum CTX) (time frame: These were measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2014.