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Bisphosphonates for Prevention of Post-Denosumab Bone Loss

Sponsor
Columbia University (Other)
Overall Status
Recruiting
CT.gov ID
NCT03396315
Collaborator
Amgen (Industry)
34
Enrollment
2
Locations
2
Arms
71.1
Anticipated Duration (Months)
17
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary goal of the study is to assess the extent to which bisphosphonate therapy will prevent decreases in bone mass that may occur after cessation of denosumab in premenopausal women with idiopathic osteoporosis (IOP) enrolled in AAAN0161 (FD05114) "Denosumab for the prevention of post-teriparatide bone loss in premenopausal women with idiopathic osteoporosis".

In addition, the investigator will observe participants for a second year off bisphosphonate therapy to assess duration of response.

The hypothesis is that bisphosphonate therapy with alendronate or zoledronic acid, initiated after recovery of bone remodeling activity, will prevent significant bone loss after discontinuing denosumab.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Osteoporosis in premenopausal women with normal menstrual function and no specific cause is termed idiopathic osteoporosis (IOP). IOP is a rare disease with an estimated prevalence of <200,000 affected premenopausal women in the United States.

Women with IOP completing at least one year and up to three years of denosumab (Protocol AAAN0161) will be offered participation in this open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg. Subjects and study personnel will be blinded to BMD outcomes until 12 months.

Discontinuation of denosumab is followed by substantial increases in bone turnover markers to well above baseline, bone resorption reaching twice baseline levels for about 6 months. Over the first 12 months off therapy, all the bone density gained on treatment is lost. Studies done at the institution has demonstrated the occurrence of multiple vertebral fractures in some patients who have stopped denosumab. Based upon these new fracture data, the Prolia label is currently recommending that consideration should be given to transition to another antiresorptive drug in patients stopping denosumab. The main goals of this extension study are to determine rates of bone loss and incidence of radiographic vertebral fractures during one year of bisphosphonate therapy (oral alendronate or intravenous zoledronic acid) initiated after completing denosumab.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
34 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg.open-label study in which they would choose whether to take oral alendronate 70 mg weekly for 12 months or a single intravenous dose of zoledronic acid 5 mg.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Bisphosphonates for Prevention of Post-Denosumab Bone Loss in Premenopausal Women With Idiopathic Osteoporosis
Actual Study Start Date :
Jan 29, 2018
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: alendronate

Subjects will receive oral alendronate

Drug: Alendronate
oral alendronate 70 mg weekly for 12 months will be given for the prevention of osteoporosis
Other Names:
  • fosamax

    		•
    Active Comparator: zoledronic acid

    Subjects will receive zoledronic acid

    Drug: Zoledronic Acid
    single intravenous dose of zoledronic acid 5 mg will be given for the prevention of osteoporosis
    Other Names:
  • Reclast

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Difference in BMD at the Lumbar spine (L1-4) within group [Baseline, 12 month]

      Within-group difference (percent change) in BMD at the lumbar spine (L1-4) will be measured by Dual-energy X-ray absorptiometry (DXA) and calculated.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 55 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • All women completing at least 12 months of Forteo treatment and at least 12 months of denosumab under previous research studies who remain without a diagnosis of an excluded medical condition and medication exposures as detailed below, will be offered enrollment into this study.
    Exclusion Criteria:

    • Known intolerance to calcium supplements

    • Contraindications to bisphosphonate treatment:

    1. Hypocalcemia

    2. Pregnancy

    3. Known hypersensitivity to bisphosphonates

    • History of osteomalacia

    • History of osteonecrosis of the jaw

    • History of dental extraction or other invasive dental surgery within the prior 4 weeks

    • Invasive dental work planned in the next 12 months

    • Any condition or illness (acute, chronic, or history), which in the opinion of the Investigator might interfere with the evaluation of efficacy and safety during the study or may otherwise compromise the safety of the subject

    • Self-reported or known alcohol or drug abuse within the previous 12 months

    • Current or recent (within 1 year of enrollment) inflammatory bowel disease or malabsorption

    • Abnormal laboratory tests performed during Visit 1

    1. Renal insufficiency or liver disease: estimated glomerular filtration rate (eGFR) < 35 ml/min, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >50% above upper limit of normal

    2. Hypercalcemia, hypocalcemia

    3. Vitamin D deficiency: 25-Hydroxyvitamin D (25-OHD) < 30 ng/mL

    • Subjects must be willing to participate voluntarily. Specifically excluded are the following: 1) women less than 20 (or 35 in the case of those who wish to participate because they have low BMD); 2) protected individuals (institutionalized); 3) prisoners; 4) any other prospective participant who, for any reason, might not be able to give voluntary informed consent.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Creighton University Omaha Nebraska United States 68131
    2 Columbia University Medical Center New York New York United States 10032

    Sponsors and Collaborators

    • Columbia University
    • Amgen

    Investigators

    • Principal Investigator: Elizabeth Shane, MD, Columbia University

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Elizabeth Shane, Professor of Medicine, Columbia University
    ClinicalTrials.gov Identifier:
    NCT03396315
    Other Study ID Numbers:
    • AAAR5220
    First Posted:
    Jan 10, 2018
    Last Update Posted:
    Jan 26, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Elizabeth Shane, Professor of Medicine, Columbia University
    premenopausal women
    Additional relevant MeSH terms:
    Osteoporosis
    Zoledronic Acid
    Alendronate

    Study Results

    No Results Posted as of Jan 26, 2021