Diabetes Mellitus, Type 2Phase 2NCT03457818

Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab

A Phase 2 study testing Denosumab 60 mg/ml [Prolia] in people with Diabetes Mellitus, Type 2 and Osteoporosis, run by Mishaela Rubin at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

Who is it for?: Ages 50 to 90 years, women only
Conditions the study is for: Diabetes Mellitus, Type 2, Osteoporosis
What is being tested?: Denosumab 60 mg/ml [Prolia]
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 8 participants
Where: 1 siteUnited States
Study dates: 7 Nov 2018to 10 Jun 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 to 90 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

Other trials in United States

About this study

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.

Read the 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.

Conditions: Diabetes Mellitus, Type 2, Osteoporosis
Being tested: Denosumab 60 mg/ml [Prolia], Placebo
Keywords: Prolia, Denosumab, Diabetes
Medical subject headings: Diabetes Mellitus, Type 2, Osteoporosis, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Denosumab 60 mg/ml [Prolia]Drug
Also called Prolia®
Denosumab 60 mg will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits
PlaceboOther
Placebo will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits

Study groups in NCT03457818
Study group	Role	What they receive
Treatment Group	Experimental	Denosumab 60 mg/ml [Prolia] SC at baseline and 6 months. Receives: Drug: Denosumab 60 mg/ml [Prolia]
Control Group	Placebo comparator	Placebo SC at Baseline and 6 months. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, 6 months and 12 months

Secondary outcomes (2)

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.
Measured: 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.
Secondary outcomes will be analyzed using ANCOVA models with P-value adjustment for multiple endpoint comparisons.
Measured: Screening visit, 6 months and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Nov 201810 Jun 2020

First posted8 Mar 2018
Study start7 Nov 2018
Primary completion10 Jun 2020
Study completion10 Jun 2020

Why it stopped: Due to enrollment difficulties compounded by the COVID pandemic.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
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 blind
Who is masked: Participant, Investigator
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03457818
Sponsor's protocol ID: AAAR7827
Status last verified: Jun 2024
First submitted: 18 Jan 2018
Last updated: 3 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 16804043
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.
PubMed 17068657
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.
PubMed 27115060
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.
PubMed 27082709

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Therapy of the Skeletal Disease of Type 2 Diabetes With Denosumab
ClinicalTrials.gov ID: NCT03457818
Acronym / sponsor ID: AAAR7827
Conditions: Diabetes Mellitus, Type 2, Osteoporosis
Keywords: Prolia, Denosumab, Diabetes
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Due to enrollment difficulties compounded by the COVID pandemic.
Enrolment: 8 participants (actual)
Lead sponsor: Mishaela RubinUniversity, hospital or other
Study start: 7 Nov 2018 (actual)
Primary completion: 10 Jun 2020 (actual)
Study completion: 10 Jun 2020 (actual)
First posted: 8 Mar 2018 (actual)
Results: Posted 11 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2
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.

Arm	Type	Receives
Treatment Group	Experimental	Drug: Denosumab 60 mg/ml [Prolia]Denosumab 60 mg/ml [Prolia] SC at baseline and 6 months.
Control Group	Placebo comparator	Other: PlaceboPlacebo SC at Baseline and 6 months.

Who may qualify

Ages: 50 to 90 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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).

Key exclusion criteria (16 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Denosumab 60 mg/ml [Prolia]Also: Prolia®Denosumab 60 mg will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits	Drug	Treatment Group
PlaceboPlacebo will be administered subcutaneously in the upper arm at the Baseline and 6 Month Visits	Other	Control Group

Primary outcome

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.

2 secondary outcomes

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
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

Results and safety

Results posted to the registry on 11 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Group	4	0
Control Group	4	0

Primary outcome: 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

Population analysed: The study was terminated due to poor enrollment compounded by the COVID-19 pandemic. Data for Primary Outcome Measure was not collected.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 1 year. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Group	0 of 4 (0%)	1 of 4 (25%)	0 of 4
Control Group	1 of 4 (25%)	1 of 4 (25%)	0 of 4

Limitations and caveats (from the sponsor): The study was terminated due to poor enrollment compounded by the COVID-19 pandemic. Data was not collected.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 16804043Bonds 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.
Background: PubMed 17068657Vestergaard 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.
Background: PubMed 27115060Furst 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.
Background: PubMed 27082709Zebaze 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mishaela Rubin, MD principal investigator

Columbia University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denosumab 60 mg/ml [Prolia] in people with Diabetes Mellitus, Type 2 and Osteoporosis, run by Mishaela Rubin at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03457818, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.