Overview
Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab
Status:
Terminated
Terminated
Trial end date:
2020-06-10
2020-06-10
Target enrollment:
0
0
Participant gender:
Female
Female
Summary
The goal of the study is to characterize the effect of Prolia® (denosumab) on indices of bone strength in type 2 diabetes (T2D). The investigational plan involves administration of Prolia® or identical placebo for 12 months as a randomized double-blind placebo-controlled trial in 66 T2D postmenopausal women assigned to Prolia® or placebo. The study will include assessment of different measures of bone quality: skeletal microarchitecture, including measurement of skeletal cortical pores; bone mineral density; bone material quality, and accumulation of advanced glycation endproducts (AGEs) in collagen. This information will help to determine whether Prolia® treatment in type 2 diabetes has skeletal benefits.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Mishaela RubinTreatments:
Denosumab
Criteria
Inclusion Criteria:1. An understanding, ability and willingness to fully comply with study procedures and
restrictions.
2. Ability to voluntarily provide written, signed and dated informed consent as
applicable to participate in the study.
3. Postmenopausal women age ≥ 50 and ≤ 90 years at time of consent.
4. Diagnosis of T2D for ≥ 2 years. Upon review of patient's medical history, patient will
be confirmed to currently have reasonably controlled T2D as assessed by the
investigator, with HbA1c ≤ 8.4%. If HbA1c is ≥ 8.5%, re-screening will be allowed
after approximately 3 months following adjustment of diabetes therapy.
5. DXA T-score ≤ -1.0 at one or more sites (lumbar spine, femoral neck, total hip or
distal 1/3 radius).
6. Normal albumin-adjusted serum calcium level.
Exclusion Criteria:
1. Hormone replacement treatment use (to avoid the influence of estrogen).
2. Fractures (excluding skull, facial bones, metacarpals, fingers, toes, and fractures
associated with severe trauma) within 12 months.
3. A history of pathological fractures (eg, due to Paget's disease, myeloma, metastatic
malignancy).
4. Type 1 diabetes.
5. Disorders associated with altered skeletal structure or function (chronic renal
disease stage 4 or worse, chronic liver disease, malignancy, hypoparathyroidism or
hyperparathyroidism, acromegaly, Cushing's syndrome, hypopituitarism, chronic
obstructive pulmonary disease, alcohol intake > 3 units/day).
6. Treatment with any of the following drugs in past year: anticonvulsant therapy,
pharmacological doses of thyroid hormone (TSH
steroids, calcitonin, estrogen or selective estrogen receptor modulator, sodium
fluoride (other than dental treatment), teriparatide, denosumab, abaloparatide,
strontium or aromatase inhibitors; any history of bisphosphonate treatment.
Corticosteroid use permitted if subject is in steady-state.
7. Serum 25(OH)D levels < 20 ng/ml. If 25(OH)D levels are < 20 ng/ml, rescreening will be
allowed following a vitamin D loading regimen of 50,000 IU/week for 4 weeks. If serum
25(OH)D levels are ≥ 20 ng/ml after supplementation, the subject will be allowed to
enroll.
8. Clinically significant hypersensitivity to denosumab or any components of denosumab 60
mg.
9. Known sensitivity to any of the products to be administered during the study (e.g.,
calcium or vitamin D).
10. Subject is pregnant or breast feeding, or planning to become pregnant within 5 months
after the end of treatment.
11. Female subject of child bearing potential and is not willing to use, in combination
with her partner, highly effective contraception during treatment and for 5 months
after the end of treatment.
12. Significant dental/oral disease, including prior history or current evidence of
osteonecrosis/osteomyelitis of the jaw, or the following:
- Active dental or jaw condition which requires oral surgery
- Non-healed dental/oral surgery
- Planned invasive dental procedures for the course of the study
13. DXA T-score of ≤ -3.5 at any site.