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Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?

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ClinicalTrials.gov Identifier: NCT01166958
Recruitment Status : Completed
First Posted : July 21, 2010
Results First Posted : September 22, 2014
Last Update Posted : September 22, 2014
Sponsor:
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE July 15, 2010
First Posted Date  ICMJE July 21, 2010
Results First Submitted Date  ICMJE June 18, 2014
Results First Posted Date  ICMJE September 22, 2014
Last Update Posted Date September 22, 2014
Study Start Date  ICMJE September 2010
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2014)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 20, 2010)
Serum markers of skeletal turnover (serum CTX and P1NP) [ Time Frame: These will be measured at the baseline and 1, 1.5, 2, 2.5, 3, 4, 5 and 6 month visits. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2014)
  • 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. ]
    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.
  • 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. ]
    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.
  • 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. ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2010)
Differences in bone mineral density of the spine, hip, forearm and total body between groups [ Time Frame: BMD will be measured at the screening, baseline, 3 month, and 6 month visits. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?
Official Title  ICMJE Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?
Brief 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 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Osteoporosis
Intervention  ICMJE
  • Drug: 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.
    Other Name: Forteo
  • Drug: Raloxifene
    Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature.
    Other Name: Evista
Study Arms  ICMJE
  • Active Comparator: Daily teriparatide (Forteo)
    Intervention: Drug: Teriparatide
  • Active Comparator: Monthly cycles of teriparatide followed by raloxifene
    Interventions:
    • Drug: Teriparatide
    • Drug: Raloxifene
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2010)
26
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

  • 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.

Exclusion Criteria:

  • 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).
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 60 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01166958
Other Study ID Numbers  ICMJE H-2010-0064
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Neil Binkley, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP