Type 2 Diabetes MellitusPhase 4NCT02608905
Effect of Dapagliflozin on Inflammation and Endothelial Function
A Phase 4 study testing Dapagliflozin in people with Type 2 Diabetes Mellitus, run by Baylor College of Medicine at 1 site in United States.
Trial summary
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce hyperglycemia and improve peripheral insulin sensitivity by ameliorating glucotoxicity. Insulin resistance in type 2 diabetes (T2DM) is associated with endothelial dysfunction and vascular inflammation. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Mar 2019
- Phase
- Phase 4
- 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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures
- Men and women, ages 21 to 70 years. i) Women of childbearing potential must be using an acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
- Women must not be pregnant or breastfeeding.
- Patients with Type 2 Diabetes Mellitus with the following parameters at study entry: hemoglobin A1c ranging from 7.0% to 9.0% and a fasting blood glucose less than or equal to 200 mg/dL.
- Patients must be on a stable dose of Metformin therapy for 3 months; the dose of metformin will not change for the duration of the study.
- Patients are allowed, but not required, to be on statins, Angiotensin Converting Enzyme (ACE) inhibitors, and angiotensin-receptor blockers at doses that have been stable for at least the last 3 months prior to enrollment in the study. Doses will not be changed for the duration of the study.
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- Patients must have a Body Mass Index between 27-35 kg/m2
- Patients must have a stable body weight for three months prior to enrollment in the study.
- Patients must have a Creatinine Clearance greater than 60 mL/min (calculated by Cockcroft-Gault formula).
- Patients must have Hematocrit greater than or equal to 34%; Serum creatinine less than1.5 mg/dl in men and 1.4 mg/dl in women and Creatinine Clearance greater than 60 ml/min; and serum aspartate aminotransferase (AST) less than 2.5 times upper limit of normal, serum alanine transaminase (ALT) less than 2.5 times upper limit of normal, serum alkaline phosphatase less than 2.5 times upper limit of normal.
Who cannot join
- History of Type 1 diabetes mellitus
- Women who are pregnant or breastfeeding
- Patients receiving lipid-lowering medications other than statins within the last 3 months.
- Patient receiving SGLT-2 inhibitors, incretin therapy, dipeptidyl peptidase 4 (DPP-4) inhibitors, thiazolidinediones, insulin, sulfonylureas, alpha-glucosidase inhibitors, corticosteroids, immunosuppressive therapy, thiazide or loop diuretics, or hormone replacement therapy within the last 3 months .
- Patient must stop treatment with nonsteroidal anti-inflammatory drugs (NSAID) and antioxidant vitamin supplements at least one week prior to the start of the study
- Patients with diabetic gastroparesis.
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- Patients with current tobacco use.
- Patients with active malignancy.
- Patients with history of urinary bladder cancer
- Patients with a history of clinically significant heart disease, peripheral vascular disease, or pulmonary disease will not be studied
- Subjects with a history of any serious hypersensitivity reaction to dapagliflozin.
- Prisoners, or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
- Patients with significant cardiac,hepatic or renal disease (Creatinine Clearance less than 60 mL/min calculated by Cockcroft-Gault formula) will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Dapagliflozin on Inflammation and Endothelial Function
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce hyperglycemia and improve peripheral insulin sensitivity by ameliorating glucotoxicity. Insulin resistance in type 2 diabetes (T2DM) is associated with endothelial dysfunction and vascular inflammation. Thus strategies to improve insulin sensitivity and lower glucotoxicity may improve endothelial inflammation and vascular inflammation. However, the effects of these agents on vascular inflammation and endothelial function is not known in patients with type 2 diabetes although anti-inflammatory properties have been demonstrated in various animal models. In the present study the investigators will assess if dapagliflozin treatment for 12 weeks decreases monocyte inflammation and improves endothelial function in patients with type 2 diabetes on metformin monotherapy.
Read the detailed description
The insulin-resistant state of type 2 diabetes mellitus (T2DM) is largely mediated by inflammatory pathways affecting skeletal muscle which is the primary site of whole body insulin resistance. Nuclear factor kappa B (NFkappaB) regulates pro-inflammatory cytokines which ultimately impair skeletal muscle insulin signaling and fatty acid oxidation; its activity reflects overall inflammatory tone in skeletal muscle. Recent human studies confirm that NFkappaB is elevated in the skeletal muscle of T2DM human subjects. Furthermore, the same inflammatory processes and signaling impairments contribute to worsening endothelial dysfunction, which is an independent predictor for future cardiovascular events in T2DM. In addition, these SGLT-2 Inhibitors reduce body weight, visceral adiposity, systolic and diastolic blood pressure, microalbuminuria, and oxidative stress. However, there are no studies examining the effects of SGLT-2 inhibitor therapy on NFkappaB and other inflammatory mediators in humans with T2DM. Moreover, no studies have examined the effect of SGLT-2 inhibitor therapy on endothelial function in this population. In the present study the investigators will assess whether dapagliflozin treatment for 12 weeks reduces monocyte inflammation and improves endothelial dysfunction in patients with type 2 diabetes on metformin monotherapy.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Dapagliflozin, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Also called Farxiga
Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.
PlaceboDrug
Patients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Experimental | Dapagliflozin 5 mg daily by mouth for 2 weeks followed by 10 mg by mouth daily for 10 weeks Receives: Drug: Dapagliflozin |
| Placebo | Placebo comparator | Placebo tablets by mouth daily for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)
The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline in patients with type 2 diabetes.
Measured: 12 weeks
Secondary outcomes (1)
Arterial Flow Mediated Dilatation (%)
The percentage change in arterial flow mediated dilation (%) from baseline as measured by ultrasound in patients with type 2 diabetes.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study startNov 2015
- Primary completionMar 2019
- Study completionMar 2019
Why it stopped: Due to difficulty with enrollment of subjects
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.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mandeep Bajaj, Baylor College of Medicine
- Investigators
- Mandeep Bajaj, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02608905
- Sponsor's protocol ID
- H-35985
- Status last verified
- Apr 2020
- First submitted
- 17 Nov 2015
- Last updated
- 8 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dapagliflozin on Inflammation and Endothelial Function
- ClinicalTrials.gov ID
- NCT02608905
- Acronym / sponsor ID
- H-35985
- Conditions
- Type 2 Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to difficulty with enrollment of subjects
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 20 Nov 2015 (estimated)
- Results
- Posted 8 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduce hyperglycemia and improve peripheral insulin sensitivity by ameliorating glucotoxicity. Insulin resistance in type 2 diabetes (T2DM) is associated with endothelial dysfunction and vascular inflammation. Thus strategies to improve insulin sensitivity and lower glucotoxicity may improve endothelial inflammation and vascular inflammation. However, the effects of these agents on vascular inflammation and endothelial function is not known in patients with type 2 diabetes although anti-inflammatory properties have been demonstrated in various animal models. In the present study the investigators will assess if dapagliflozin treatment for 12 weeks decreases monocyte inflammation and improves endothelial function in patients with type 2 diabetes on metformin monotherapy.
Detailed description
The insulin-resistant state of type 2 diabetes mellitus (T2DM) is largely mediated by inflammatory pathways affecting skeletal muscle which is the primary site of whole body insulin resistance. Nuclear factor kappa B (NFkappaB) regulates pro-inflammatory cytokines which ultimately impair skeletal muscle insulin signaling and fatty acid oxidation; its activity reflects overall inflammatory tone in skeletal muscle. Recent human studies confirm that NFkappaB is elevated in the skeletal muscle of T2DM human subjects. Furthermore, the same inflammatory processes and signaling impairments contribute to worsening endothelial dysfunction, which is an independent predictor for future cardiovascular events in T2DM. In addition, these SGLT-2 Inhibitors reduce body weight, visceral adiposity, systolic and diastolic blood pressure, microalbuminuria, and oxidative stress. However, there are no studies examining the effects of SGLT-2 inhibitor therapy on NFkappaB and other inflammatory mediators in humans with T2DM. Moreover, no studies have examined the effect of SGLT-2 inhibitor therapy on endothelial function in this population. In the present study the investigators will assess whether dapagliflozin treatment for 12 weeks reduces monocyte inflammation and improves endothelial dysfunction in patients with type 2 diabetes on metformin monotherapy.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Experimental | Drug: DapagliflozinDapagliflozin 5 mg daily by mouth for 2 weeks followed by 10 mg by mouth daily for 10 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablets by mouth daily for 12 weeks |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of informed consent prior to any study specific procedures
- Men and women, ages 21 to 70 years. i) Women of childbearing potential must be using an acceptable method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized.
- Patients with Type 2 Diabetes Mellitus with the following parameters at study entry: hemoglobin A1c ranging from 7.0% to 9.0% and a fasting blood glucose less than or equal to 200 mg/dL.
- Patients must be on a stable dose of Metformin therapy for 3 months; the dose of metformin will not change for the duration of the study.
- Patients are allowed, but not required, to be on statins, Angiotensin Converting Enzyme (ACE) inhibitors, and angiotensin-receptor blockers at doses that have been stable for at least the last 3 months prior to enrollment in the study. Doses will not be changed for the duration of the study.
Key exclusion criteria (14 listed)
- History of Type 1 diabetes mellitus
- Women who are pregnant or breastfeeding
- Patients receiving lipid-lowering medications other than statins within the last 3 months.
- Patient receiving SGLT-2 inhibitors, incretin therapy, dipeptidyl peptidase 4 (DPP-4) inhibitors, thiazolidinediones, insulin, sulfonylureas, alpha-glucosidase inhibitors, corticosteroids, immunosuppressive therapy, thiazide or loop diuretics, or hormone replacement therapy within the last 3 months .
- Patient must stop treatment with nonsteroidal anti-inflammatory drugs (NSAID) and antioxidant vitamin supplements at least one week prior to the start of the study
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 |
|---|---|---|
| DapagliflozinAlso: FarxigaPatients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo. | Drug | Dapagliflozin |
| PlaceboPatients with Type 2 diabetes will be randomized to receive dapagliflozin 5 mg daily for 2 weeks followed by10 mg daily for 10 weeks by mouth or matching placebo for 12 weeks. All subjects will receive measurements of fasting plasma glucose, Free Fatty Acids, inflammatory markers and adipocytokines, monocyte inflammation, as well as ultrasound assessment of flow-mediated dilatation (FMD) of the brachial artery at baseline and after 12 weeks of drug treatment with either dapagliflozin or placebo. | Drug | Placebo |
Primary outcome
Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)
Time frame: 12 weeks
The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline in patients with type 2 diabetes.
1 secondary outcome
Arterial Flow Mediated Dilatation (%)
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Mandeep Bajaj, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin in people with Type 2 Diabetes Mellitus, run by Baylor College of Medicine 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 10 inclusion and 14 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 8 Apr 2020. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 8 Apr 2020). 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?
Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2020.