Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab

August 1, 2022 updated by: Mishaela Rubin
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Type 2 Diabetes Mellitus (T2DM) has become one of the most important diseases of our time. Recent research shows that diabetes has negative effects on bones and that people with diabetes might be more likely to break a bone. We don't know the reasons for this, but we suspect that normal bone replacement is slowed down in diabetes and this could slow down the growth of new bone. It is possible that the normal bone material becomes weaker because sugar-related components ("Advanced Glycation Endproducts") are making the bone more brittle. The investigators have shown in past research that people who have type 2 diabetes are more likely to have both weaker bone with lower "bone material strength" and also higher levels of sugar-related components ("Advanced Glycation Endproducts"). This study will focus on attempting to lower the sugar-related components ("Advanced Glycation Endproducts") by treating a group of patients with type 2 diabetes with a medication Prolia® or denosumab for one year. The investigators will compare postmenopausal women both before and after denosumab use and study them in terms of different bone features based on blood tests, bone imaging, a bone indentation test and a measurement of sugar-related components in the skin. This study will help to clarify if using this medication helps improve bone strength in women with diabetes.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center - Harkness Pavillion

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment Group
Denosumab 60 mg/ml [Prolia] SC at baseline and 6 months.
Drug: Denosumab 60 mg/ml [Prolia]
Denosumab 60 mg will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits
Other Names:
  • Prolia®
Placebo Comparator: Control Group
Placebo SC at Baseline and 6 months.
Other: Placebo
Placebo will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Cortical Porosity (Ct.Po) (%) by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging From Baseline to 6 and 12 Months.
Time Frame: Baseline, 6 months and 12 months
The primary outcome is the 12 months change in Ct.Po and the primary intent-to-treat analysis is a one-way ANCOVA with the fixed effect of treatment (treated vs. placebo), and baseline Ct.Po as a continuous covariate.
Baseline, 6 months and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Collagen Type I C-Telopeptide (s-CTX) (ng/ml) and Tartrate-resistant Acid Phosphatase 5b (TRAP 5b) (ng/ml) by Blood Test From Baseline to 3, 6 and 12 Months.
Time Frame: Baseline, 3 months, 6 months and 12 months
Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.
Baseline, 3 months, 6 months and 12 months
Change in Dual-energy X-ray Absorptiometry (DXA) (gm/cm2) at Lumbar Spine, Femoral Neck, Total Hip and Radius From Baseline to 6 and 12 Months.
Time Frame: Screening visit, 6 months and 12 months
Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.
Screening visit, 6 months and 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Skin Autofluorescence (SAF) (Unitless) From Baseline to 6 and 12 Months.
Time Frame: Baseline, 6 months and 12 months
Exploratory outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.
Baseline, 6 months and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mishaela Rubin

Investigators

  • Principal Investigator: Mishaela Rubin, MD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 7, 2018

Primary Completion (Actual)

June 10, 2020

Study Completion (Actual)

June 10, 2020

Study Registration Dates

First Submitted

January 18, 2018

First Submitted That Met QC Criteria

March 6, 2018

First Posted (Actual)

March 8, 2018

Study Record Updates

Last Update Posted (Actual)

August 3, 2022

Last Update Submitted That Met QC Criteria

August 1, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAR7827

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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