NCT02576652

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Dec 2015

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 26, 2015

Completed
5 months until next milestone

First Posted

Study publicly available on registry

October 15, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

December 22, 2015

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 18, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 18, 2017

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

April 26, 2019

Completed
Last Updated

April 26, 2019

Status Verified

April 1, 2019

Enrollment Period

2 years

First QC Date

May 26, 2015

Results QC Date

December 6, 2018

Last Update Submit

April 8, 2019

Conditions

Keywords

bone biopsytetracyclinedemeclocyclinetotal hip replacement

Outcome Measures

Primary Outcomes (1)

  • 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.

    Days 22-58 (at the time of hip replacement surgery)

Secondary Outcomes (3)

  • Modeling Based Formation Units in the Femoral Neck

    Days 22-58 (at the time of hip replacement surgery)

  • Overfilled Remodeling-based Formation Units in the Femoral Neck

    Days 22-58 (at the time of hip replacement surgery)

  • Remodeling-based Formation Units Including Overfilled Units in the Femoral Neck

    Days 22-58 (at the time of hip replacement surgery)

Study Arms (1)

Osteoarthritis Participants

OTHER

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.

Other: TetracyclineOther: DemeclocyclineProcedure: Total Hip Replacement

Interventions

Treatment during cycle 1 consists of a total oral dose of 1000 mg of tetracycline daily for a total of 3 days.

Osteoarthritis Participants

Treatment during cycle 2 consists of a total oral dose of 600 mg of demeclocycline daily for 3 days.

Osteoarthritis Participants

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.

Osteoarthritis Participants

Eligibility Criteria

Age50 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Helen Hayes Hospital

West Haverstraw, New York, 10993, United States

Location

Research Site

West Haverstraw, New York, 10993, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Osteoporosis

Interventions

TetracyclineDemeclocyclineArthroplasty, Replacement, Hip

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

TetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsArthroplasty, ReplacementArthroplastyOrthopedic ProceduresSurgical Procedures, OperativePlastic Surgery ProceduresProsthesis Implantation

Results Point of Contact

Title
Study Director
Organization
Amgen Inc.

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 26, 2015

First Posted

October 15, 2015

Study Start

December 22, 2015

Primary Completion

December 18, 2017

Study Completion

December 18, 2017

Last Updated

April 26, 2019

Results First Posted

April 26, 2019

Record last verified: 2019-04

Locations