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Osteoclast Inhibition and Bone Formation

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT02554695
Collaborator
(none)
81
Enrollment
1
Location
3
Arms
12.2
Actual Duration (Months)
6.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This protocol addresses: 1) How gene expression changes in bone cells are affected by aging? 2) Is aging associated with decreased signaling between bone cells? 3) How does treatment with the osteoporosis medication denosumab affect bone cell signaling?

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Detailed Description

This protocol collectively addresses the following goals: 1) What are the changes in gene expression in osteoblasts and osteocytes that lead to impaired bone formation with aging; 2) Since recent work from the investigators' group has demonstrated that osteoclasts produce a number of growth factors and cytokines (coupling factors) that enhance osteoblast proliferation and/or differentiation, is aging associated with reduced osteoclast coupling factor production; and 3) If osteoclasts are markedly reduced using the FDA-approved medication for osteoporosis, denosumab, how does that effect the quantity of coupling factors in the bone microenvironment and the target genes of these coupling factors in osteoblasts?

Study Design

Study Type:
Interventional
Actual Enrollment :
81 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Basic Science
Official Title:
Effects of Age and Osteoclast Inhibition on Bone Formation
Actual Study Start Date :
Oct 20, 2015
Actual Primary Completion Date :
Oct 25, 2016
Actual Study Completion Date :
Oct 25, 2016

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: placebo

single subcutaneous injection of placebo (normal saline)

Drug: placebo
subcutaneous saline injection
Other Names:
  • saline

    		•
    Active Comparator: Denosumab

    single subcutaneous injection of denosumab 60 mg

    Drug: denosumab
    single subcutaneous injection of denosumab 60 mg
    Other Names:
  • Prolia

    		•
    No Intervention: young normal premenopausal women

    no intervention

    Outcome Measures

    Primary Outcome Measures

    1. Gene expression changes in bone cells [3 months]

      Ratio of selected genes as expressed between each of the 3 arms (i.e. relative runx2 gene expression levels in each arm).

    Secondary Outcome Measures

    1. Osteoclast-osteoblast coupling factor changes [3 months]

      Ratio of selected genes as expressed between each of the 3 arms (i.e. relative runx2 gene expression levels in each arm).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    25 Years to 80 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes

    • Inclusion Criteria:

    • normal premenopausal women aged 25-40 years

    • normal postmenopausal women aged 60-80 years

    • at least 5 yrs since their last menses

    • follicle stimulating hormone (FSH) > 20 IU/L

    • Exclusion Criteria:

    • Abnormality in any of the screening laboratory studies

    • Presence of significant liver or renal disease

    • Malignancy (including myeloma)

    • Malabsorption

    • Diabetes

    • Hypoparathyroidism

    • Hyperparathyroidism

    • Acromegaly

    • Cushing's syndrome

    • Hypopituitarism

    • Severe chronic obstructive pulmonary disease

    • Undergoing treatment with any medications that affect bone turnover, including the following:

    • adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)

    • anticonvulsant therapy (within the previous year)

    • pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)

    • calcium supplementation of > 1200 mg/d (within the preceding 3 months)

    • bisphosphonates (within the past 3 yrs)

    • denosumab

    • estrogen (E) therapy within the past year

    • treatment with a selective E receptor modulator within the past year

    • teriparatide within the past yr

    • Clinical history of osteoporotic fracture (vertebral, hip, or distal forearm)

    • Recent (within the past 6 months) fracture

    • Serum 25-hydroxyvitamin D levels of < 20 ng/ml

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic

    Investigators

    • Principal Investigator: Sundeep Khosla, MD, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sundeep Khosla, M.D., PI, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT02554695
    Other Study ID Numbers:
    • 15-002313
    First Posted:
    Sep 18, 2015
    Last Update Posted:
    Jan 5, 2018
    Last Verified:
    Jan 1, 2018
    Keywords provided by Sundeep Khosla, M.D., PI, Mayo Clinic
    adrenergic
    Additional relevant MeSH terms:
    Denosumab

    Study Results

    No Results Posted as of Jan 5, 2018