Bone Modeling Effects of Combined Anabolic/Antiresorptive Administration

NCT04026256 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 2018P0025375R01AR073191-04
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine, via iliac crest bone biopsies, the mechanism of combined teriparatide and denosumab on the bone of postmenopausal osteoporotic women after 3 months of treatment.

Conditions

Postmenopausal Osteoporosis

Keywords

osteoporosis; histomorphometry; bone density; teriparatide; denosumab

Outcome Measures

Primary Outcomes (1)

• Cancellous Bone Formation Rate at Month 3

  Cancellous bone formation rate at month 3 is calculated from the cancellous (trabecular) compartment of the iliac crest bone biopsy specimens. Bone formation rate (BFR/BS, mm3/mm2/day): amount of new bone formed in unit time per unit of bone surface. It is calculated by multiplying the mineralizing surface/bone surface (MS/BS) by the mineral apposition rate (MAR) - see below for how MS/BS and MAR are calculated. Mineralizing surface (MS/BS, %): is the percent of bone surface that displays a tetracycline label reflecting active mineralization. It is calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface. It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. Mineral apposition rate (MAR mm/day): is the mean distance between the double labels, divided by the time interval between them.

  3 months after first dose of study drug

Study Arms (3)

Teriparatide only

ACTIVE COMPARATOR

daily subcutaneous injection teriparatide for 3 months

Drug: Teriparatide

Denosumab only

ACTIVE COMPARATOR

one dose of subcutaneous injection denosumab

Drug: Denosumab

Denosumab and teriparatide

ACTIVE COMPARATOR

daily subcutaneous injection teriparatide for 3 months plus one dose of subcutaneous injection denosumab

Drug: Teriparatide; Drug: Denosumab

Interventions

Teriparatide DRUG

teriparatide daily subcutaneous injection

Also known as: Forteo

Denosumab and teriparatide; Teriparatide only

Denosumab DRUG

denosumab subcutaneous injection

Also known as: Prolia

Denosumab and teriparatide; Denosumab only

Eligibility Criteria

• Age: 45 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• women aged 45+
• postmenopausal
• osteoporotic with high risk of fracture

You may not qualify if:

• significant previous use of bone health modifying treatments
• 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/mL or \>60ng/mL
• serum alkaline phosphatase above upper normal limit with no explanation
• anemia (hematocrit \<32%)
• history of malignancy (except non-melanoma skin carcinoma), radiation therapy, or gouty arthritis
• history of urolithiasis within the last one year
• excessive alcohol use or substance abuse
• use of oral or parenteral glucocorticoids for more than 14 days within the past 6 months
• extensive dental work involving extraction or dental implant within the past or upcoming 2 months
• known sensitivity to mammalian cell-derived drug products
• known contraindications to denosumab, teriparatide, or any of their excipients
• known contraindications to tetracycline, demeclocycline, or other antibiotics in this drug class

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Osteoporosis, Postmenopausal; Osteoporosis

Interventions

Teriparatide; Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Benjamin Leder
• Organization: Massachusetts General Hospital

bzleder@mgh.harvard.edu

617-724-2039

Study Officials

• Benjamin Leder, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Study Start: September 2, 2019
• Primary Completion: April 18, 2022
• Study Completion: April 18, 2022
• Last Updated: August 2, 2023
• Results First Posted: August 2, 2023

Record last verified: 2023-08

Locations

US (1)