Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab
Condition: Diabetes Mellitus, Type 2; Osteoporosis
MeSH terms: Osteoporosis; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Denosumab 60 mg/ml [Prolia]; Placebo
Intervention description: Denosumab 60 mg will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits; Placebo will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits
Intervention MeSH terms: Denosumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study is a 12 month randomized (2:1 assignment) double-blind placebo-controlled trial of T2D postmenopausal women assigned to either Denosumab 60 mg subcutaneously (SC) at baseline and 6 months (n=44) or placebo (n=22); total study n=66.
Masking: Double (Participant, Investigator)
Masking description: Clinical Research Coordinators
Enrollment: 8.0
Sex: Female
Minimum age: 50 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Prolia; Denosumab; Diabetes

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.
    

Eligibility 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<normal is permitted if subject has
             normal T4, clinical euthyroidism and is in steady-state), adrenal or anabolic
             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.