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Trial record 2 of 974 for:    "Osteoporosis"

A Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00887965
First received: April 23, 2009
Last updated: October 23, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Low Bone Mass
Low Bone Mineral Density
Osteoporosis
Postmenopausal Osteoporosis
Drug: Previous denosumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Transiliac Crest Bone Histology and Histomorphometry Study in Postmenopausal Women With Low Bone Mass or Osteoporosis Previously Treated With Denosumab

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Number of Participants With Normal/Abnormal Bone Histology [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Bone Histomorphometry: Cancellous Bone Volume [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Trabecular Number [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Trabecular Separation [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Trabecular separation (Tb.Sp) is the mean distance in mm between trabeculae (measured by integrated computer graphics). Tb.Sp increases with trabecular bone loss.

  • Bone Histomorphometry: Trabecular Thickness [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Cortical Width [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Cortical width correlates with dual photon absorptiometric (DPX) measurements of bone density.

  • Bone Histomorphometry: Surface Density [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Surface density is calculated by total bone (trabecular) surfaces / total tissue volume.

  • Bone Histomorphometry: Osteoblast - Osteoid Interface [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Osteoblast - osteoid interface is calculated as osteoblast surface / osteoid surface * 100.

  • Bone Histomorphometry: Osteoid Surface [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Osteoid surface is expressed as a percentage total bone surface.

  • Bone Histomorphometry: Osteoid Width [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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).

  • Bone Histomorphometry: Wall Thickness [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Wall thickness is the average thickness of trabecular bone structural units (BSU) and is used to assess the overall balance between resorption and formation.

  • Bone Histomorphometry: Eroded Surface/Bone Surface [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Eroded surface is expressed as a percentage of total bone surface.

  • Bone Histomorphometry: Osteoclast Number - Length Based [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Osteoclast Number - Surface Based [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Single-label Surface [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Double-label Surface [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Total Mineralizing Surface [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Total mineralizing surfaces (MS) include all double and half of single-labeled surfaces. MS is expressed as a percentage of total bone surface.

  • Bone Histomorphometry: Mineral Apposition Rate [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Adjusted Mineral Apposition Rate [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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).

  • Bone Histomorphometry: Bone Formation Rate - Surface Based [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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).

  • Bone Histomorphometry: Bone Formation Rate - Volume Based [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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).

  • Bone Histomorphometry: Formation Period [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Activation Frequency [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    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.

  • Bone Histomorphometry: Osteoid Volume [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    Osteoid volume is expressed as a percentage of total bone volume.

  • Bone Histomorphometry: Mineralization Lag Time [ Time Frame: 25-34 days post-Day 1 ] [ Designated as safety issue: No ]
    The mineralization lag time is the time interval between osteoid secretion and its subsequent mineralization, in days.

  • C-Telopeptide (CTX-1) [ Time Frame: Day 3 or Day 20 ] [ Designated as safety issue: No ]
    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.

  • Procollagen Type 1 N-terminal Peptide (P1NP) [ Time Frame: Day 3 or Day 20 ] [ Designated as safety issue: No ]
    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.


Enrollment: 15
Study Start Date: June 2009
Study Completion Date: August 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Previous denosumab
Participants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative.
Drug: Previous denosumab
Participants who had previously received denosumab received a transiliac crest bone biopsy performed following standard labeling procedures with tetracycline or tetracycline derivative.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887965

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00887965     History of Changes
Other Study ID Numbers: 20080287
Study First Received: April 23, 2009
Results First Received: June 30, 2011
Last Updated: October 23, 2013
Health Authority: Argentina: ANMAT (Administracion Nacional de Medicamentos Alimentos y Tecnologia Medica)
Argentina: Ministry of Health
Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by Amgen:
Low Bone Mass
Low Bone Mineral Density
Osteoporosis
Postmenopausal Osteoporosis
Bone Biopsy
Transiliac Crest Bone Histology
Histomorphometry

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on November 19, 2014