Low Bone MassPhase 2NCT00887965
A Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab
A Phase 2 study testing Previous denosumab in people with Low Bone Mass and Low Bone Mineral Density, run by Amgen.
Trial summary
To characterize the effects of discontinuation of denosumab therapy on variables of bone histology in postmenopausal women with low bone mass or osteoporosis. Patients who have received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463)… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Low Bone Mass, Low Bone Mineral Density, Osteoporosis
- What is being tested?
- Previous denosumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- Jun 2009to Aug 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Ambulatory postmenopausal women
- Received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463), completed study 20030216 (NCT00089791) but did not enroll in study 20060289 (NCT00523341). Patients who will participate in the off-treatment imaging study for 20080747 (NCT00890981) also are eligible.
- Completed participation in eligible studies ≥ 12 and ≤ 36 months prior to screening
- Provide signed informed consent
Who cannot join
- Did not receive denosumab in studies 20050141, 20060237, 20030216, or 20050179.
- Discontinued investigational product before end of study visit for studies 20050141, 20060237, 20030216, or 20050179.
- Received > 1 month osteoporosis treatment since having completed studies 20050141, 20060237, 20030216, or 20050179.
- Received zoledronic acid at any time after ending study participation in parent studies 20050141, 20050179, 20030216, or 20060237.
- Newly diagnosed with any of the following conditions during the intervening period since completing studies 20050141, 20060237, 20030216, or 20050179:
- Hyperthyroidism (stable on anti-thyroid therapy or post-ablation is allowed, if the Thyroid Stimulating Hormone is within the normal range)
Show all 22Show fewer
- Hypothyroidism (stable on thyroid replacement therapy is allowed, if the Thyroid Stimulating Hormone is within the normal range)
- Hyper- or hypoparathyroidism
- Osteomalacia
- Paget's disease of bone
- Other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis imperfecta)
- 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.
- Permanently non-ambulatory subjects (use of assistive device eg cane, walker is permitted).
- Has known or suspected sensitivity or contraindication to tetracycline derivatives.
- Received any investigational product other than denosumab.
- Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone analogue, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium or tibolone.
- Has undergone bilateral transiliac crest bone biopsy in the past.
- Current use of medications that, in the opinion of the investigator, cannot be discontinued and may compromise the safety of the subject when undergoing the bone biopsy procedure (eg, aspirin, warfarin, high-dose heparin).
- Current use of systemic glucocorticoid therapy (topical or nasal steroids are permitted).
- Evidence of coagulopathy that in the opinion of the investigator, may compromise patient safety when subjected to the bone biopsy procedure.
- Any disorder that, in the opinion of the investigator, may compromise the ability of the participant to give written informed consent and/or comply with study procedures.
About this study
To characterize the effects of discontinuation of denosumab therapy on variables of bone histology in postmenopausal women with low bone mass or osteoporosis. Patients who have received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463), completed study 20030216 (NCT00089791) but did not enroll in study 20060289 (NCT00523341) will be included in this study. Patients who will participate in the off-treatment imaging study for 20080747 (NCT00890981) are also eligible.
- Being tested
- Previous denosumab
- Keywords
- Low Bone Mass, Low Bone Mineral Density, Osteoporosis, Postmenopausal Osteoporosis, Bone Biopsy, Transiliac Crest Bone Histology, Histomorphometry
- Medical subject headings
- Bone Diseases, Metabolic, Osteoporosis, Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Previous denosumabDrug
Participants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative.
| Study group | Role | What they receive |
|---|---|---|
| Previous denosumab | Other | Participants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative. Receives: Drug: Previous denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Normal/Abnormal Bone Histology
The number of participants with normal/abnormal bone histology as assessed by bone biopsy samples at the central histomorphometric facility. Normal bone histology is characterized by: - normal lamellar bone, - normal mineralization or - osteoid (the organic matrix of bone; young bone that has not undergone calcification). Biopsies with abnormal bone histology are characterized by: - osteomalacia, - marrow fibrosis, - clinically significant marrow abnormality or - woven bone.
Measured: 25-34 days post-Day 1
Secondary outcomes (26)
Bone Histomorphometry: Cancellous Bone Volume
Cancellous (trabecular) bone volume (Tb.V) is the relative volume of total cancellous bone measured (TV), expressed as percentage, that is occupied by trabeculae. Cancellous bone volume was measured using Fluorochrome labeling with tetracyclene and tartrate-resistant acid phosphatase stain (TRAP) staining techniques.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Trabecular Number
Trabecular number (Tb.N) is the number of trabeculae present per lineal mm and is calculated as trabecular bone volume/trabecular thickness. Tb.N is a measure of trabecular connectivity and decreases with bone loss.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Trabecular Separation
Trabecular separation (Tb.Sp) is the mean distance in mm between trabeculae (measured by integrated computer graphics). Tb.Sp increases with trabecular bone loss.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Trabecular Thickness
Mean trabecular thickness (Tb.Th) is a measure of trabecular structure and is calculated as the reciprocal of total bone (trabecular) surfaces. Tb.Th is reduced by aging and osteoporosis.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Cortical Width
Cortical width correlates with dual photon absorptiometric (DPX) measurements of bone density.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Surface Density
Surface density is calculated by total bone (trabecular) surfaces / total tissue volume.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Osteoblast - Osteoid Interface
Osteoblast - osteoid interface is calculated as osteoblast surface / osteoid surface * 100.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Osteoid Surface
Osteoid surface is expressed as a percentage total bone surface.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Osteoid Width
Osteoid thickness (width; O.Th) is the mean thickness of osteoid seams on cancellous surfaces. O.Th is normally <12.5 µm. Increased O.Th suggests abnormal mineralization (osteomalacia).
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Wall Thickness
Wall thickness is the average thickness of trabecular bone structural units (BSU) and is used to assess the overall balance between resorption and formation.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Eroded Surface/Bone Surface
Eroded surface is expressed as a percentage of total bone surface.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Osteoclast Number - Length Based
Osteoclast number expressed per mm of bone. Osteoclast number was measured using fluorochrome labeling with tetracyclene and tartrate-resistant acid phosphatase stain (TRAP) staining techniques.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Osteoclast Number - Surface Based
Osteoclast number expressed per bone surface area. Osteoclast number was measured using fluorochrome labeling with tetracyclene and tartrate-resistant acid phosphatase stain (TRAP) staining techniques.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Single-label Surface
Single-label surface is expressed as a percentage of total bone surface. The presence of a single label indicates that mineralization was occurring during only one labeling period.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Double-label Surface
Double-label surface is expressed as a percentage of total bone surface. The presence of double labels indicates that normal bone mineralization was actively occurring over the labeling interval.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Total Mineralizing Surface
Total mineralizing surfaces (MS) include all double and half of single-labeled surfaces. MS is expressed as a percentage of total bone surface.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Mineral Apposition Rate
The mineral apposition rate (MAR) is the avarage rate at which new bone mineral is being added on any actively forming surface. MAR is calculated as the average distance between visible labels, divided by the labeling interval.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Adjusted Mineral Apposition Rate
The mineral apposition rate (MAR) is the avarage rate at which new bone mineral is being added on any actively forming surface. Adjusted MAR is calculated as: (average distance between visible labels / labeling interval) * (total mineralizing surface/total bone surface).
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Bone Formation Rate - Surface Based
Bone formation rate - surface based (BFR/BS) is the calculated rate at which cancellous bone surface is being replaced annually. BFR/BS is derived from the Mineral Appositional Rate * 365 * (relative mineralizing surface /total bone surface).
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Bone Formation Rate - Volume Based
Bone formation rate - volume based (BFR/BV) is the calculated rate at which cancellous bone volume is being replaced annually. BFR/BV is derived from the Mineral Appositional Rate * 365 * (relative mineralizing surface / total bone volume).
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Formation Period
The formation period is the duration of an interval when a place on the bone surface is actively forming bone. The formation period is calculated as the wall width (thickness of new bone made in one cycle) divided by the mineral apposition rate.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Activation Frequency
The average time that it takes for a new remodeling cycle to begin on any point on a cancellous surface is called the activation frequency (Ac.f). Activation frequency is calculated as the bone formation rate / wall width.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Osteoid Volume
Osteoid volume is expressed as a percentage of total bone volume.
Measured: 25-34 days post-Day 1
Bone Histomorphometry: Mineralization Lag Time
The mineralization lag time is the time interval between osteoid secretion and its subsequent mineralization, in days.
Measured: 25-34 days post-Day 1
C-Telopeptide (CTX-1)
C-Telopeptide is a biochemical marker for bone turnover. Blood samples were drawn for assessment of CTX-1 levels on either Day 3 or Day 20, within 24 hours of the last dose of the respective tetracycline cycle.
Measured: Day 3 or Day 20
Procollagen Type 1 N-terminal Peptide (P1NP)
Procollagen Type 1 N-terminal Peptide is a biochemical marker of bone turnover. Blood samples were drawn for assessment of P1NP levels on either Day 3 or Day 20, within 24 hours of the last dose of the respective tetracycline cycle.
Measured: Day 3 or Day 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2009 (estimated)
- Study startJun 2009
- Primary completionJun 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Low Bone MassStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00887965
- Sponsor's protocol ID
- 20080287
- Status last verified
- Oct 2013
- First submitted
- 23 Apr 2009
- Last updated
- 15 Nov 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab
- ClinicalTrials.gov ID
- NCT00887965
- Acronym / sponsor ID
- 20080287
- Keywords
- Low Bone Mass, Low Bone Mineral Density, Osteoporosis, Postmenopausal Osteoporosis, Bone Biopsy, Transiliac Crest Bone Histology, Histomorphometry
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Jun 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 24 Apr 2009 (estimated)
- Results
- Posted 17 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To characterize the effects of discontinuation of denosumab therapy on variables of bone histology in postmenopausal women with low bone mass or osteoporosis. Patients who have received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463), completed study 20030216 (NCT00089791) but did not enroll in study 20060289 (NCT00523341) will be included in this study. Patients who will participate in the off-treatment imaging study for 20080747 (NCT00890981) are also eligible.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Previous denosumab | Other | Drug: Previous denosumabParticipants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Ambulatory postmenopausal women
- Received denosumab and completed study 20050179 (NCT00293813), completed study 20050141 (NCT00330460), completed study 20060237 (NCT00515463), completed study 20030216 (NCT00089791) but did not enroll in study 20060289 (NCT00523341). Patients who will participate in the off-treatment imaging study for 20080747 (NCT00890981) also are eligible.
- Completed participation in eligible studies ≥ 12 and ≤ 36 months prior to screening
- Provide signed informed consent
Key exclusion criteria (22 listed)
- Did not receive denosumab in studies 20050141, 20060237, 20030216, or 20050179.
- Discontinued investigational product before end of study visit for studies 20050141, 20060237, 20030216, or 20050179.
- Received > 1 month osteoporosis treatment since having completed studies 20050141, 20060237, 20030216, or 20050179.
- Received zoledronic acid at any time after ending study participation in parent studies 20050141, 20050179, 20030216, or 20060237.
- Newly diagnosed with any of the following conditions during the intervening period since completing studies 20050141, 20060237, 20030216, or 20050179:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Previous denosumabParticipants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative. | Drug | Previous denosumab |
Primary outcome
Number of Participants With Normal/Abnormal Bone Histology
Time frame: 25-34 days post-Day 1
The number of participants with normal/abnormal bone histology as assessed by bone biopsy samples at the central histomorphometric facility. Normal bone histology is characterized by: - normal lamellar bone, - normal mineralization or - osteoid (the organic matrix of bone; young bone that has not undergone calcification). Biopsies with abnormal bone histology are characterized by: - osteomalacia, - marrow fibrosis, - clinically significant marrow abnormality or - woven bone.
26 secondary outcomes
Bone Histomorphometry: Cancellous Bone Volume
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Trabecular Number
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Trabecular Separation
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Trabecular Thickness
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Cortical Width
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Surface Density
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Osteoblast - Osteoid Interface
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Osteoid Surface
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Osteoid Width
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Wall Thickness
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Eroded Surface/Bone Surface
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Osteoclast Number - Length Based
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Osteoclast Number - Surface Based
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Single-label Surface
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Double-label Surface
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Total Mineralizing Surface
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Mineral Apposition Rate
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Adjusted Mineral Apposition Rate
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Bone Formation Rate - Surface Based
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Bone Formation Rate - Volume Based
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Formation Period
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Activation Frequency
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Osteoid Volume
Time frame: 25-34 days post-Day 1
Bone Histomorphometry: Mineralization Lag Time
Time frame: 25-34 days post-Day 1
C-Telopeptide (CTX-1)
Time frame: Day 3 or Day 20
Procollagen Type 1 N-terminal Peptide (P1NP)
Time frame: Day 3 or Day 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Previous denosumab in people with Low Bone Mass and Low Bone Mineral Density, run by Amgen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Normal/Abnormal Bone Histology (time frame: 25-34 days post-Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2013.