Back to results

Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab

Primary Purpose

Diabetes Mellitus, Type 2, Osteoporosis

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Denosumab 60 mg/ml [Prolia]

Placebo

About this trial

This is an interventional prevention trial for Diabetes Mellitus, Type 2 focused on measuring Prolia, Denosumab, Diabetes

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

An understanding, ability and willingness to fully comply with study procedures and restrictions.
Ability to voluntarily provide written, signed and dated informed consent as applicable to participate in the study.
Postmenopausal women age ≥ 50 and ≤ 90 years at time of consent.
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.
DXA T-score ≤ -1.0 at one or more sites (lumbar spine, femoral neck, total hip or distal 1/3 radius).
Normal albumin-adjusted serum calcium level.

Exclusion Criteria:

Hormone replacement treatment use (to avoid the influence of estrogen).
Fractures (excluding skull, facial bones, metacarpals, fingers, toes, and fractures associated with severe trauma) within 12 months.
A history of pathological fractures (eg, due to Paget's disease, myeloma, metastatic malignancy).
Type 1 diabetes.
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).
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.
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.
Clinically significant hypersensitivity to denosumab or any components of denosumab 60 mg.
Known sensitivity to any of the products to be administered during the study (e.g., calcium or vitamin D).
Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment.
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.
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
DXA T-score of ≤ -3.5 at any site.

Sites / Locations

Columbia University Irving Medical Center - Harkness Pavillion

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment Group

Control Group

Arm Description

Denosumab 60 mg/ml [Prolia] SC at baseline and 6 months.

Placebo SC at Baseline and 6 months.

Outcomes

Primary Outcome Measures

Change in Cortical Porosity (Ct.Po) (%) by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging From Baseline to 6 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.

Secondary Outcome Measures

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.

Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.

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.

Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.

Full Information

NCT ID

NCT03457818

First Posted

January 18, 2018

Last Updated

August 1, 2022

Sponsor

Mishaela Rubin

1. Study Identification

Unique Protocol Identification Number

NCT03457818

Brief Title

Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab

Official Title

Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Terminated

Why Stopped

Due to enrollment difficulties compounded by the COVID pandemic.

Study Start Date

November 7, 2018 (Actual)

Primary Completion Date

June 10, 2020 (Actual)

Study Completion Date

June 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mishaela Rubin

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2, Osteoporosis

Keywords

Prolia, Denosumab, Diabetes

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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

ParticipantInvestigator

Masking Description

Clinical Research Coordinators

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment Group

Arm Type

Experimental

Arm Description

Denosumab 60 mg/ml [Prolia] SC at baseline and 6 months.

Arm Title

Control Group

Arm Type

Placebo Comparator

Arm Description

Placebo SC at Baseline and 6 months.

Intervention Type

Drug

Intervention Name(s)

Denosumab 60 mg/ml [Prolia]

Other Intervention Name(s)

Prolia®

Intervention Description

Denosumab 60 mg will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits

Primary Outcome Measure Information:

Title

Change in Cortical Porosity (Ct.Po) (%) by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging From Baseline to 6 and 12 Months.

Description

Time Frame

Baseline, 6 months and 12 months

Secondary Outcome Measure Information:

Title

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.

Description

Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.

Time Frame

Baseline, 3 months, 6 months and 12 months

Title

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.

Description

Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.

Time Frame

Screening visit, 6 months and 12 months

Other Pre-specified Outcome Measures:

Title

Change in Skin Autofluorescence (SAF) (Unitless) From Baseline to 6 and 12 Months.

Description

Exploratory outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.

Time Frame

Baseline, 6 months and 12 months

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: An understanding, ability and willingness to fully comply with study procedures and restrictions. Ability to voluntarily provide written, signed and dated informed consent as applicable to participate in the study. Postmenopausal women age ≥ 50 and ≤ 90 years at time of consent. 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. DXA T-score ≤ -1.0 at one or more sites (lumbar spine, femoral neck, total hip or distal 1/3 radius). Normal albumin-adjusted serum calcium level. Exclusion Criteria: Hormone replacement treatment use (to avoid the influence of estrogen). Fractures (excluding skull, facial bones, metacarpals, fingers, toes, and fractures associated with severe trauma) within 12 months. A history of pathological fractures (eg, due to Paget's disease, myeloma, metastatic malignancy). Type 1 diabetes. 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). 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. 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. Clinically significant hypersensitivity to denosumab or any components of denosumab 60 mg. Known sensitivity to any of the products to be administered during the study (e.g., calcium or vitamin D). Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment. 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. 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 DXA T-score of ≤ -3.5 at any site.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mishaela Rubin, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Irving Medical Center - Harkness Pavillion

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

16804043

Citation

Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL. Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study. J Clin Endocrinol Metab. 2006 Sep;91(9):3404-10. doi: 10.1210/jc.2006-0614. Epub 2006 Jun 27.

Results Reference

background

PubMed Identifier

17068657

Citation

Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int. 2007 Apr;18(4):427-44. doi: 10.1007/s00198-006-0253-4. Epub 2006 Oct 27.

Results Reference

background

PubMed Identifier

27115060

Citation

Furst JR, Bandeira LC, Fan WW, Agarwal S, Nishiyama KK, McMahon DJ, Dworakowski E, Jiang H, Silverberg SJ, Rubin MR. Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes. J Clin Endocrinol Metab. 2016 Jun;101(6):2502-10. doi: 10.1210/jc.2016-1437. Epub 2016 Apr 26.

Results Reference

background

PubMed Identifier

27082709

Citation

Zebaze R, Libanati C, McClung MR, Zanchetta JR, Kendler DL, Hoiseth A, Wang A, Ghasem-Zadeh A, Seeman E. Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis. J Bone Miner Res. 2016 Oct;31(10):1827-1834. doi: 10.1002/jbmr.2855. Epub 2016 May 19.

Results Reference

background

Learn more about this trial

Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab

We'll reach out to this number within 24 hrs