Back to resultsBone Histomorphometry in Postmenopausal Men and Women With Osteoarthritis Undergoing Total Hip Replacement
Primary Purpose
Osteoporosis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Tetracycline
Demeclocycline
Total Hip Replacement
Sponsored by
About this trial
This is an interventional basic science trial for Osteoporosis focused on measuring bone biopsy, tetracycline, demeclocycline, total hip replacement
Eligibility Criteria
Inclusion Criteria:
- Subject has provided informed consent/assent prior to initiation of any study-specific activities/procedures
- Ambulatory postmenopausal women and men with osteoporosis
- Scheduled to undergo elective THR due to osteoarthritis of the hip
- Received at least 2 doses of denosumab 60 mg subcutaneously over 18 months
- Last dose of denosumab within 6 months of scheduled THR
Exclusion Criteria:
- Received treatment for osteoporosis other than denosumab in one year prior to THR
Subjects with current diagnosis of any of the following conditions are excluded
- Current, uncontrolled hypo- or hyperthyroidism (subjects who have controlled hypo- or hyperthyroidism may be eligible, provided that they have been on a stable therapy for at least 3 months [per subject report])
- Current, hypo- or hyperparathyroidism
- Osteomalacia
- Paget's disease of bone
- Other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta)
- Severe chronic kidney disease (CKD), defined as CKD stage 4 or greater
- Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
- Self-reported alcohol or drug abuse within the previous 12 months
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s)
- Other investigational procedures while participating in this study are excluded
- Subject has known sensitivity to any of the products to be administered (eg, tetracycline, demeclocycline) during study
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Sites / Locations
- Helen Hayes Hospital
- Research Site
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Osteoarthritis Participants
Arm Description
Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Outcomes
Primary Outcome Measures
Percentage of Participants With Modeling Based Bone Formation in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line.
The percentage of participants with fluorochrome labeling present in the cancellous or periosteal, or endocortical surfaces of the femoral neck indicative of modeling-based bone formation is reported.
Secondary Outcome Measures
Modeling Based Formation Units in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line. The number of modeling based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Overfilled Remodeling-based Formation Units in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Remodeling-based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of overfilled remodeling-based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported as units per mm of bone surface.
Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Remodeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of remodeling based formation units including overfilled units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02576652
Brief Title
Bone Histomorphometry in Postmenopausal Men and Women With Osteoarthritis Undergoing Total Hip Replacement
Official Title
Bone Histomorphometry of the Proximal Femur in Denosumab-treated Subjects Undergoing Total Hip Replacement
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
December 22, 2015 (Actual)
Primary Completion Date
December 18, 2017 (Actual)
Study Completion Date
December 18, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to determine the incidence of modeling-based bone formation in the femoral neck in participants who have received denosumab and are undergoing total hip replacement (THR).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis
Keywords
bone biopsy, tetracycline, demeclocycline, total hip replacement
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Osteoarthritis Participants
Arm Type
Other
Arm Description
Participants previously treated with denosumab and planning to undergo total hip replacement (THR) received one cycle of tetracycline administered at either 250 mg four times a day or 500 mg twice a day for 3 days and one cycle of demeclocycline administered at either 150 mg four times a day or 300 mg twice a day for 3 days, ten days after last dose of tetracycline in cycle 1. THR surgery was performed 5 to 42 days after the last dose of demeclocycline.
Intervention Type
Other
Intervention Name(s)
Tetracycline
Intervention Description
Treatment during cycle 1 consists of a total oral dose of 1000 mg of tetracycline daily for a total of 3 days.
Intervention Type
Other
Intervention Name(s)
Demeclocycline
Intervention Description
Treatment during cycle 2 consists of a total oral dose of 600 mg of demeclocycline daily for 3 days.
Intervention Type
Procedure
Intervention Name(s)
Total Hip Replacement
Intervention Description
Participants entering this study were prescheduled to undergo elective THR due to osteoarthritis. Surgery was to be performed according to local standard of care. During THR a fragment of femoral bone was acquired for histomorphometry evaluation.
Primary Outcome Measure Information:
Title
Percentage of Participants With Modeling Based Bone Formation in the Femoral Neck
Description
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line.
The percentage of participants with fluorochrome labeling present in the cancellous or periosteal, or endocortical surfaces of the femoral neck indicative of modeling-based bone formation is reported.
Time Frame
Days 22-58 (at the time of hip replacement surgery)
Secondary Outcome Measure Information:
Title
Modeling Based Formation Units in the Femoral Neck
Description
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Modeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a smooth cement line. The number of modeling based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Time Frame
Days 22-58 (at the time of hip replacement surgery)
Title
Overfilled Remodeling-based Formation Units in the Femoral Neck
Description
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Remodeling-based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of overfilled remodeling-based formation units was evaluated at the cancellous, periosteal, and endocortical regions and is reported as units per mm of bone surface.
Time Frame
Days 22-58 (at the time of hip replacement surgery)
Title
Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck
Description
Femoral neck bone samples were prepared according to standard procedures for bone histology and bone histomorphometry at a central bone histomorphometry facility.
Remodeling based formation units in active bone-forming, tetracycline-labeled surfaces were identified by a scalloped cement line. The number of remodeling based formation units including overfilled units was evaluated at the cancellous, periosteal, and endocortical regions and is reported in units per mm of bone surface.
Time Frame
Days 22-58 (at the time of hip replacement surgery)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject has provided informed consent/assent prior to initiation of any study-specific activities/procedures
Ambulatory postmenopausal women and men with osteoporosis
Scheduled to undergo elective THR due to osteoarthritis of the hip
Received at least 2 doses of denosumab 60 mg subcutaneously over 18 months
Last dose of denosumab within 6 months of scheduled THR
Exclusion Criteria:
Received treatment for osteoporosis other than denosumab in one year prior to THR
Subjects with current diagnosis of any of the following conditions are excluded
Current, uncontrolled hypo- or hyperthyroidism (subjects who have controlled hypo- or hyperthyroidism may be eligible, provided that they have been on a stable therapy for at least 3 months [per subject report])
Current, hypo- or hyperparathyroidism
Osteomalacia
Paget's disease of bone
Other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta)
Severe chronic kidney disease (CKD), defined as CKD stage 4 or greater
Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma)
Self-reported alcohol or drug abuse within the previous 12 months
Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s)
Other investigational procedures while participating in this study are excluded
Subject has known sensitivity to any of the products to be administered (eg, tetracycline, demeclocycline) during study
Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Helen Hayes Hospital
City
West Haverstraw
State/Province
New York
ZIP/Postal Code
10993
Country
United States
Facility Name
Research Site
City
West Haverstraw
State/Province
New York
ZIP/Postal Code
10993
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32163613
Citation
Dempster DW, Chines A, Bostrom MP, Nieves JW, Zhou H, Chen L, Pannacciulli N, Wagman RB, Cosman F. Modeling-Based Bone Formation in the Human Femoral Neck in Subjects Treated With Denosumab. J Bone Miner Res. 2020 Jul;35(7):1282-1288. doi: 10.1002/jbmr.4006. Epub 2020 Apr 2.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Bone Histomorphometry in Postmenopausal Men and Women With Osteoarthritis Undergoing Total Hip Replacement
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