Enhancing Osteoporosis Therapy: Can We Open the Anabolic Window?

NCT01166958 | Completed Phase 4 Results DMC

• 1 other identifier: H-2010-0064
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (2)

• 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.

Secondary Outcomes (3)

• Average Bone Mineral Density of the Spine at Baseline, 3 Months and 6 Months

  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

  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

  BMD measured at the baseline, 3 month, and 6 month visits.

Study Arms (2)

Daily teriparatide (Forteo)

ACTIVE COMPARATOR

Drug: Teriparatide

Monthly cycles of teriparatide followed by raloxifene

ACTIVE COMPARATOR

Drug: Teriparatide; Drug: Raloxifene

Interventions

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.

Also known as: Forteo

Daily teriparatide (Forteo); Monthly cycles of teriparatide followed by raloxifene

Raloxifene DRUG

Raloxifene (RLX; Evista) is supplied as a 60 mg tablet. RLX is stored at room temperature.

Also known as: Evista

Monthly cycles of teriparatide followed by raloxifene

Eligibility Criteria

• Age: 60 Years - 89 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin Osteoporosis Clinical Center and Research Program

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

Teriparatide; Raloxifene Hydrochloride

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Neil Binkley, MD
• Organization: University of Wisconsin Osteoporosis Clinical Research Program

uwosteoporosis@gmail.com

608-265-6410

Study Officials

• Neil Binkley, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 21, 2010
• Study Start: September 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: September 22, 2014
• Results First Posted: September 22, 2014

Record last verified: 2014-09

Locations

US (1)