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µMRI of Therapeutic Intervention in Postmenopausal Osteoporosis (TERIZOL)

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ClinicalTrials.gov Identifier: NCT01153425
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : August 4, 2017
Last Update Posted : August 4, 2017
Sponsor:
Collaborators:
Eli Lilly and Company
Novartis Pharmaceuticals
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Osteoporosis, Osteopenia
Interventions Other: Virtual Bone Biopsy
Drug: Teriparatide
Drug: Zoledronic Acid
Enrollment 33
Recruitment Details Participants were recruited from the Philadelphia region via various modes of public advertisements (radio, newspapers, flyers).
Pre-assignment Details To qualify for participation participants must have BMD T-scores of either the spine (L1-L4) or total hip of ≤ -2.5 or a history of osteoporotic fracture.
Arm/Group Title Teriparatide (Forteo) Zoledronic Acid (Reclast)
Hide Arm/Group Description

20 µg of Teriparatide will be self-injected subcutaneously once a day for 24 months and an MRI ('Virtual Bone Biopsy') will be performed at 0 and 24 months.

Virtual Bone Biopsy by Magnetic Resonance Imaging: The MRI involves virtual bone biopsy technology currently being developed. This new technology is not commercially or elsewhere available. It allows generation of 3D images of considerably smaller voxel size than the previous technology by employing new pulse sequences and advanced interpolation techniques. The enhanced resolution will enable capturing subtle remodeling-induced changes, such as reversal of the fenestration caused by prior osteoclastic resorption cavities. It will also permit measurement of trabecular thickness with increased accuracy and precision. Advances have also been made toward superior registration of follow-up scans relative to the baseline scans. This, we project, provides improved reproducibility and thus increased statistical power.

5 mg of zoledronic Acid will be administered intravenously at baseline and 12 months and an MRI ('Virtual Bone Biopsy) will be performed at 0 and 24 months.

Virtual Bone Biopsy by Magnetic Resonance Imaging: The MRI involves virtual bone biopsy technology currently being developed. This new technology is not commercially or elsewhere available. It allows generation of 3D images of considerably smaller voxel size than the previous technology by employing new pulse sequences and advanced interpolation techniques. The enhanced resolution will enable capturing subtle remodeling-induced changes, such as reversal of the fenestration caused by prior osteoclastic resorption cavities. It will also permit measurement of trabecular thickness with increased accuracy and precision. Advances have also been made toward superior registration of follow-up scans relative to the baseline scans. This, we project, provides improved reproducibility and thus increased statistical power.

Period Title: Overall Study
Started 16 17
Completed 13 14
Not Completed 3 3
Reason Not Completed
Withdrawal by Subject             3             3
Arm/Group Title Teriparatide (Forteo) Zoledronic Acid (Reclast) Total
Hide Arm/Group Description

20 µg of Teriparatide will be self-injected subcutaneously once a day for 24 months and an MRI ('Virtual Bone Biopsy') will be performed at 0 and 24 months.

Virtual Bone Biopsy by Magnetic Resonance Imaging: The MRI involves virtual bone biopsy technology currently being developed. This new technology is not commercially or elsewhere available. It allows generation of 3D images of considerably smaller voxel size than the previous technology by employing new pulse sequences and advanced interpolation techniques. The enhanced resolution will enable capturing subtle remodeling-induced changes, such as reversal of the fenestration caused by prior osteoclastic resorption cavities. It will also permit measurement of trabecular thickness with increased accuracy and precision. Advances have also been made toward superior registration of follow-up scans relative to the baseline scans. This, we project, provides improved reproducibility and thus increased statistical power.

5 mg of zoledronic Acid will be administered intravenously at baseline and 12 months and an MRI ('Virtual Bone Biopsy) will be performed at 0 and 24 months.

Virtual Bone Biopsy by Magnetic Resonance Imaging: The MRI involves virtual bone biopsy technology currently being developed. This new technology is not commercially or elsewhere available. It allows generation of 3D images of considerably smaller voxel size than the previous technology by employing new pulse sequences and advanced interpolation techniques. The enhanced resolution will enable capturing subtle remodeling-induced changes, such as reversal of the fenestration caused by prior osteoclastic resorption cavities. It will also permit measurement of trabecular thickness with increased accuracy and precision. Advances have also been made toward superior registration of follow-up scans relative to the baseline scans. This, we project, provides improved reproducibility and thus increased statistical power.

Total of all reporting groups
Overall Number of Baseline Participants 16 17 33
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 16 participants 17 participants 33 participants
69.55
(58 to 84)
66.22
(58 to 84)
67.94
(58 to 84)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 17 participants 33 participants
Female
16
 100.0%
17
 100.0%
33
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: Post menopausal females
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 17 participants 33 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
16
 100.0%
17
 100.0%
33
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 17 participants 33 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
12
  75.0%
12
  70.6%
24
  72.7%
More than one race
4
  25.0%
5
  29.4%
9
  27.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Change in Trabecular Surface-to-curve Ratio
Hide Description Ratio of the volume densities of surface (S) and curve (C)-type voxels, S/C
Time Frame Change between baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Mean change in structural and mechanical markers of bone turnover between the two groups.
Arm/Group Title Teriparatide (Forteo) Zoledronic Acid (Reclast)
Hide Arm/Group Description:

20 µg of Teriparatide self-injected subcutaneously once a day for 24 months with MRI performed at 0, 12 and 24 months.

The data showed strong increases in finite element derived axial stiffness and improvement in structural parameters indicative of a more connected, more plate-like topology at the 12 and 24-month time points: bone marrow density (BMD), bone volume fraction (BVF), the topological parameters surface-to-curve ratio (S/C), which is a measure of the bone's "platelikeness", erosion index (EI), a parameter expressing the loss of connectivity, and axial stiffness (Ezz), all changed in the direction suggesting an improvement of bone quality.

No difference was detected between the two treatment arms.

5 mg of zoledronic Acid administered intravenously at baseline and 12 months and MRI performed at 0, 12, and 24 months.

The data showed strong increases in finite element derived axial stiffness and improvement in structural parameters indicative of a more connected, more plate-like topology at the 12 and 24-month time points: bone marrow density (BMD), bone volume fraction (BVF), the topological parameters surface-to-curve ratio (S/C), which is a measure of the bone's "platelikeness", erosion index (EI), a parameter expressing the loss of connectivity, and axial stiffness (Ezz), all changed in the direction suggesting an improvement of bone quality.

No difference was detected between the two treatment arms.

Overall Number of Participants Analyzed 13 14
Mean (Standard Deviation)
Unit of Measure: Percentage of Change
9.1  (2.0) 7.1  (2.6)
2.Secondary Outcome
Title Percentage of Change in Bone Volume Fraction (BVF)
Hide Description Average fractional content of bone expressed in percent
Time Frame Change between baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Teriparatide (Forteo) Zoledronic Acid (Reclast)
Hide Arm/Group Description:

20 µg of Teriparatide self-injected subcutaneously once a day for 24 months with MRI performed at 0 and 24 months.

The data showed strong increases in finite element derived axial stiffness and improvement in structural parameters indicative of a more connected, more plate-like topology at the 12 and 24-month time points: bone marrow density (BMD), bone volume fraction (BVF), the topological parameters surface-to-curve ratio (S/C), which is a measure of the bone's "platelikeness", erosion index (EI), a parameter expressing the loss of connectivity, and axial stiffness (Ezz), all changed in the direction suggesting an improvement of bone quality.

No difference was detected between the two treatment arms.

5 mg of zoledronic Acid administered intravenously at baseline and 12 months and MRI performed at 0, 12, and 24 months.

The data showed strong increases in finite element derived axial stiffness and improvement in structural parameters indicative of a more connected, more plate-like topology at the 12 and 24-month time points: bone marrow density (BMD), bone volume fraction (BVF), the topological parameters surface-to-curve ratio (S/C), which is a measure of the bone's "platelikeness", erosion index (EI), a parameter expressing the loss of connectivity, and axial stiffness (Ezz), all changed in the direction suggesting an improvement of bone quality.

No difference was detected between the two treatment arms.

Overall Number of Participants Analyzed 13 14
Mean (Standard Deviation)
Unit of Measure: Percentage of Change
1.0  (0.8) 0.6  (0.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Teriparatide (Forteo), Zoledronic Acid (Reclast)
Comments paired t-test for change from baseline to 24 months
Type of Statistical Test Other
Comments unpaired t-test for the difference of the means between the two arms
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 2 years
Adverse Event Reporting Description Adverse events were monitored/assessed without regard to the specific adverse event term. Please note that adverse events do include abnormal laboratory values at screening.
 
Arm/Group Title Teriparatide (Forteo) Zoledronic Acid (Reclast)
Hide Arm/Group Description

20 µg of teriparatide will be self-injected subcutaneously once a day for 24 months and an MRI ('Virtual Bone Biopsy') will be performed at 0 and 24 months.

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.

Teriparatide: Participants are clinically indicated for treatment.

5 mg of zoledronic Acid will be administered intravenously at baseline and 12 months and an MRI ('Virtual Bone Biopsy) will be performed at 0 and 24 months.

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.

Zoledronic Acid: Participants are clinically indicated for treatment.

All-Cause Mortality
Teriparatide (Forteo) Zoledronic Acid (Reclast)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)      0/17 (0.00%)    
Hide Serious Adverse Events
Teriparatide (Forteo) Zoledronic Acid (Reclast)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/16 (6.25%)      0/17 (0.00%)    
Surgical and medical procedures     
Serious * [1]  1/16 (6.25%)  1 0/17 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Surgical intervention for meningioma
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Teriparatide (Forteo) Zoledronic Acid (Reclast)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/16 (93.75%)      12/17 (70.59%)    
Blood and lymphatic system disorders     
Moderate * [1]  2/16 (12.50%)  3 0/17 (0.00%)  0
Mild  [2]  7/16 (43.75%)  9 6/17 (35.29%)  12
Eye disorders     
Moderate * [3]  1/16 (6.25%)  1 0/17 (0.00%)  0
Mild * [4]  0/16 (0.00%)  0 1/17 (5.88%)  1
Gastrointestinal disorders     
Moderate *  0/16 (0.00%)  0 1/17 (5.88%)  1
General disorders     
Moderate *  0/16 (0.00%)  0 2/17 (11.76%)  2
Mild * [5]  9/16 (56.25%)  11 4/17 (23.53%)  4
Respiratory, thoracic and mediastinal disorders     
Mild * [6]  1/16 (6.25%)  1 1/17 (5.88%)  1
Skin and subcutaneous tissue disorders     
Moderate * [7]  1/16 (6.25%)  1 0/17 (0.00%)  0
Moderate * [8]  1/16 (6.25%)  1 0/17 (0.00%)  0
Moderate * [9]  0/16 (0.00%)  0 1/17 (5.88%)  1
Surgical and medical procedures     
Moderate * [10]  0/16 (0.00%)  0 1/17 (5.88%)  1
Moderate * [11]  1/16 (6.25%)  1 0/17 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Hypercalcemia
Indicates events were collected by systematic assessment
[2]
Abnormal lab values
[3]
Beginning of detached retina
[4]
Eye Redness
[5]
Non-Specific
[6]
Sinus Infection
[7]
Abrasions from fall
[8]
Dog bite
[9]
Edema of finger
[10]
Extractions due to dental disease
[11]
Surgical repair of uterine prolapse
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Felix W. Wehrli, Ph.D.
Organization: University of Pennsylvania, Perelman School of Medicine
Phone: 215-662-7951
EMail: wehrli@mail.med.upenn.edu
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01153425    
Other Study ID Numbers: 803763
R01AR041443 ( U.S. NIH Grant/Contract )
First Submitted: June 1, 2009
First Posted: June 30, 2010
Results First Submitted: May 22, 2017
Results First Posted: August 4, 2017
Last Update Posted: August 4, 2017