NCT03623633

Brief Summary

Osteoporosis remains a significant healthcare burden for the United States. Current FDA-approved osteoporosis treatments include teriparatide, abaloparatide, bisphosphonates, denosumab, and raloxifene. Denosumab is a fully human monoclonal antibody that specifically binds to receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab potently suppresses osteoclastic activity but bone turnover rapidly normalizes and bone turnover marker levels can rebound above baseline levels after the drug is discontinued. This study will help us determine the optimal duration and relative efficacy of two oral antiresorptive medications that are FDA-approved for treatment of postmenopausal osteoporosis (alendronate and raloxifene) in preventing the rebound increase in bone turnover that occurs after denosumab discontinuation.

Trial Health

55
Monitor

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
51

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Nov 2018

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
active not recruiting

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

August 6, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 9, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

November 30, 2018

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2023

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2023

Completed
Last Updated

June 7, 2023

Status Verified

June 1, 2023

Enrollment Period

4.2 years

First QC Date

August 6, 2018

Last Update Submit

June 5, 2023

Conditions

Osteoporosis, PostmenopausalOsteoporosis

Outcome Measures

Primary Outcomes (2)

  • Serum c-telopeptide (CTX)

    Change in serum CTX between month 12 and month 18

    Month 12 to 18 months

  • Bone mineral density (BMD)

    Change in PA spine BMD between month 24 and month 36

    Month 24 to 36 months

Study Arms (2)

Denosumab and Raloxifene

ACTIVE COMPARATOR

denosumab and raloxifene

Drug: denosumabDrug: raloxifene

Denosumab and Alendronate

ACTIVE COMPARATOR

denosumab and alendronate

Drug: denosumabDrug: alendronate

Interventions

denosumabDRUG

denosumab 60 milligrams subcutaneously every 6 months

Also known as: Prolia
Denosumab and AlendronateDenosumab and Raloxifene
alendronateDRUG

alendronate 70 milligrams weekly

Also known as: Fosamax
Denosumab and Alendronate
raloxifeneDRUG

raloxifene 60 milligrams daily

Also known as: Evista
Denosumab and Raloxifene

Eligibility Criteria

Age45 Years+
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsPostmenopausal women
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • women aged 45+
  • postmenopausal
  • osteoporotic with high risk of fracture as per National Osteoporosis Foundation guidelines

You may not qualify if:

  • no significant previous use of bone health modifying treatments
  • hip fracture within one year of enrollment
  • known congenital or acquired bone disease other than osteoporosis
  • significant renal disease, liver disease, cardiopulmonary disease, or psychiatric disease
  • abnormal calcium or parathyroid hormone level
  • serum vitamin D \<20 ng/dL
  • anemia (hematocrit \<32%)
  • history of malignancy (except non-melanoma skin carcinoma)
  • excessive alcohol use or substance abuse
  • extensive dental work involving extraction or dental implant within the past 6 months or in the upcoming 12 months
  • known contraindications to denosumab, alendronate, or raloxifene

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

  • Tsai JN, Jordan M, Lee H, Leder BZ. One versus 2 years of alendronate following denosumab: the CARD extension. Osteoporos Int. 2024 Dec;35(12):2225-2230. doi: 10.1007/s00198-024-07213-2. Epub 2024 Aug 7.

    PMID: 39112628DERIVED

MeSH Terms

Conditions

Osteoporosis, PostmenopausalOsteoporosis

Interventions

DenosumabAlendronateRaloxifene Hydrochloride

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsDiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsTamoxifenStilbenesBenzylidene CompoundsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons

Study Officials

  • Joy Tsai, MD

    MGH

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor, Harvard Medical School

Study Record Dates

First Submitted

August 6, 2018

First Posted

August 9, 2018

Study Start

November 30, 2018

Primary Completion

February 1, 2023

Study Completion

August 1, 2023

Last Updated

June 7, 2023

Record last verified: 2023-06

Locations

US(1)