µMRI of Therapeutic Intervention in Postmenopausal Osteoporosis (TERIZOL)

NMR Imaging and Stereological Analysis of Trabecular Bone in Female Subjects 60 and Older at Risk of Fracture Receiving Either Zoledronic Acid or Teriparatide

The purpose of this study is to apply a novel advanced magnetic resonance imaging methodology to evaluate the response to drug intervention involving two treatment arms of postmenopausal participants with osteoporosis, randomized into either a teriparatide (Forteo™) or zoledronic acid (Reclast™) group.

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Osteopenia
• Intervention / Treatment: Other: Virtual Bone Biopsy; Drug: Teriparatide; Drug: Zoledronic Acid

Detailed Description

The overall design is to determine and compare the effect of teriparatide and of zoledronic acid on trabecular architecture by magnetic resonance imaging of the midshaft tibia. Post-menopausal women, aged 60 or older with osteoporosis and/or at increased risk of fracture, will be randomized to receive either teriparatide or zoledronic acid. Trabecular microarchitecture, biomechanical parameters and bone mineral density will be examined at 0 and 12 months at 3T MRI.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women
• Age ≥ 60 years
• Bone mineral density T-score of either the spine (L1-L4), total hip or femoral neck of ≤ - 2.0, or has a history of an osteoporotic fracture

Exclusion Criteria:

• Previous treatment with pamidronate, ibandronate, of more than 2 doses in 2 years and of zoledronic acid at any time
• Previous treatment with teriparatide, alendronate or risedronate of more than 2 months in the last 24 months
• Previous treatment with calcitonin within the previous year; previous treatment with an estrogen or selective estrogen modulator will not exclude a potential subject unless she has been taking it for < 1 year (a woman who discontinued estrogen or a selective estrogen receptor within the previous year will also be excluded)
• Other diseases known to affect bone, such as Paget's disease, Cushing's disease, hyperthyroidism, hyperparathyroidism, bone cancer and metastases to bone, and vitamin D deficiency
• Medications known to affect bone, such as anticonvulsants, high dose glucocorticoids (20 mg/day or more > 2 weeks within the previous 6 months)
• Current alcohol use > 3 drinks/day
• Untreated or unstable cardiac, pulmonary, liver (SGOT > 2X upper limit of normal) or renal disease (creatinine > 1.2 mg/dL) or uncontrolled diabetes (hemoglobin A1C > 8.0)
• Prior radiation therapy to the skeleton
• Cardiac pacemakers, ferromagnetic implants or brain aneurysm clips
• Claustrophobia
• Subjects whose initial MRI is of poor quality due to motion artifact will be asked to repeat the examination; if a repeat MRI is of poor quality due to motion artifact, the subject will be excluded from the study
• Abnormalities of the which delay esophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
• Hypocalcemia
• Uric acid level >7.5ml/dl
• Subjects with metallic objects in their bodies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Teriparatide (Forteo); 20 µg of Teriparatide will be self-injected subcutaneously once a day for 12 months and an MRI at 3T ('Virtual Bone Biopsy') will be performed at 0 and 12 months.	Other: Virtual Bone Biopsy; MRI technology allowing generation of 3D images with considerably smaller voxel size than previous technology through the use of novel pulse sequences and advanced interpolation techniques.; Other Names: VBB; Drug: Teriparatide; Participants are clinically indicated for treatment.; Other Names: Forteo
Active Comparator: Zoledronic Acid (Reclast); 5 mg of zoledronic Acid will be administered intravenously at baseline and 12 months and an MRI at 3T ('Virtual Bone Biopsy) will be performed at 0 and 12 months.	Other: Virtual Bone Biopsy; MRI technology allowing generation of 3D images with considerably smaller voxel size than previous technology through the use of novel pulse sequences and advanced interpolation techniques.; Other Names: VBB; Drug: Zoledronic Acid; Participants are clinically indicated for treatment.; Other Names: Reclast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Change in Trabecular Surface-to-curve Ratio	Ratio of the volume densities of surface (S) and curve (C)-type voxels, S/C	Change between baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Change in Bone Volume Fraction (BVF)	Average fractional content of bone expressed in percent	Change between baseline and 12 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Eli Lilly and Company; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Novartis Pharmaceuticals
• Investigators: Principal Investigator: Felix W. Wehrli, Ph.D., University of Pennsylvania, Department of Radiology; Study Director: Peter J. Snyder, M.D., University Of Pennsylvania, Department of Endocrinology

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: June 1, 2009
• First Submitted That Met QC Criteria: June 28, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 1, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Osteoporosis; Osteopenia; Fracture Risk; teriparatide or Forteo; zoledronic acid or Reclast
• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Zoledronic Acid; Teriparatide
• Other Study ID Numbers: 803763; R01AR041443 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No