Type 2 DiabetesPhase 4NCT02796170
Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes
A Phase 4 study testing Dapagliflozin in people with Type 2 Diabetes and Hypertension, run by Tulane University School of Medicine at 1 site in United States.
Trial summary
To assess the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on blood pressure and urinary angiotensinogen. This is a cross over study design, where 40 subjects will receive Dapagliflozin for 6 weeks followed by placebo for 6 weeks, or placebo for 6 weeks followed by Dapagliflozin for 6 weeks. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 2 Diabetes, Hypertension
- 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
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to Aug 2020
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetes with hypertension and on RAAS blocking drugs OR
- Type 2 diabetes without hypertension and not on RAAS blocking drugs
- Hemoglobin A1c between 7% and 9% (inclusive)
- Estimated glomerular filtration rate (eGFR) ≥60 ml/min
- Capacity to understand and sign informed consent
Who cannot join
- Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3x upper limit of normal (ULN)
- Total bilirubin >2.0 mg/dL
- Positive serologic evidence of current infectious liver disease, including Hepatitis B viral antibody immunoglobulin M (IGM), Hepatitis B surface antigen, and Hepatitis C virus antibody
- Estimated glomerular filtration rate (eGFR) <60 ml/min
- Recent cardiovascular events with the last 2 months: acute coronary syndrome (ACS), hospitalization for unstable angina or acute myocardial infarction, acute stroke or transient ischemic attack (TIA), or post coronary artery revascularization
- Congestive Heart Failure defined as New York Heart Association (NYHA) class IV, unstable or acute congestive heart failure
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- Pregnant or breastfeeding patients
- Patients who, in the judgement of the investigator, may be at risk for dehydration
- Blood pressure at enrollment: Systolic ≥165 mmHg and/or Diastolic ≥110 mmHg; At randomization: Systolic ≥160 mmHg and/or Diastolic ≥100 mmHg
- Use of SGLT-2 inhibitor class drugs is an exclusion for all patients. For patients in the sulfonylurea arm, use of sulfonylurea class drugs is an exclusion.
Trial locations and contacts
1 site in 1 country.
About this study
To assess the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on blood pressure and urinary angiotensinogen. This is a cross over study design, where 40 subjects will receive Dapagliflozin for 6 weeks followed by placebo for 6 weeks, or placebo for 6 weeks followed by Dapagliflozin for 6 weeks. In addition there will be an arm of 10 subjects who will receive sulfonylurea in an open label as a comparative to the cross over subjects to assess if the effect of Dapagliflozin may also be in part due to improved glycemic control.
Read the detailed description
Clinical trials of two SGLT2 inhibitors, canagliflozin and dapagliflozin, have reported drops in systolic blood pressure of ~5 mmHg. Inappropriate activation of intrarenal renin-angiotensin system (RAS) is a major contributor to the increased arterial pressure and tissue injury including diabetic nephropathy. A key factor in the intrarenal RAS activation is stimulation of intrarenal angiotensinogen (AGT) which is the precursor of angiotensin peptides. From previous studies, it has been shown that high blood sugars in patients with type1 and type 2 diabetes mellitus is accompanied by elevated intrarenal AGT and urinary AGT levels. High glucose results in stimulation of AGT production. The high glucose levels augments intrarenal AGT levels in diabetes mellitus leading to the development of high blood pressure and diabetic nephropathy.
The investigators propose to conduct a single-center randomized, double blind, cross over study of the effect of Dapagliflozin over 6 weeks, followed by placebo over 6 weeks on the other treatment allocation (those getting placebo first will cross over to Dapagliflozin and vice versa). Treatment will be stratified according to the underlying presence or absence of hypertension.
- Type 2 diabetes with hypertension and on renin-angiotensin-aldosterone system (RAAS) blocking drugs with stable blood pressure on therapy; n= 20
- Type 2 diabetes without hypertension and not on RAAS blocking drugs n=10
If unable to recruit 10 participants without hypertension the investigators will increase the number with hypertension for a total of 30. Stratification by hypertension status will remain and is important in understanding the effect of SGLT2 inhibition in patients not on BP lowering drugs.
In addition a Sulfonylurea (SU) arm will also be included - 10 participants who are on metformin and other background therapy (with the exclusion of SGLT-2 inhibitor and sulfonylurea) will be recruited. This will be an open-labeled arm. Participants will assessed at baseline. Participants will then receive usual care for 6 weeks. At the end of 6 weeks, participants will then undergo another assessment before being provided SU for 6 weeks. At the end of 6 weeks, participants will undergo assessment again. The aim is to determine whether any effects seen with Dapagliflozin are specific to that drug or related simply to improved glycemic control.
- Conditions
- Type 2 Diabetes, Hypertension
- Being tested
- Dapagliflozin, Placebo
- Keywords
- SGLT-2 inhibitor, urinary angiotensinogen
- Medical subject headings
- Diabetes Mellitus, Type 2, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
5mg pill taken once daily
PlaceboDrug
5mg pill taken once daily- placebo of Dapagliflozin
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Active comparator | Participants underwent 6 weeks of Dapagliflozin or placebo (washout period for 2 weeks) and then crossed over to 6 weeks of placebo or Dapagliflozin. Receives: Drug: Dapagliflozin; Drug: Placebo |
| Placebo | Active comparator | Participants underwent 6 weeks of Dapagliflozin or placebo (washout period for 2 weeks) and then crossed over to 6 weeks of placebo or Dapagliflozin. Receives: Drug: Dapagliflozin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Blood Pressure From Baseline to 6 Weeks Measured by ABPM
Blood pressure was measured at baseline with a 24 hour ambulatory blood pressure machine (ABPM), and again after 6 weeks of treatment.
Measured: Baseline to 6 weeks
Secondary outcomes (1)
Change in Urinary AGT Levels From Baseline to 6 Weeks
Urinary Angiotensinogen (AGT) was measured through the collection of 24 hour urine at baseline and again after 6 weeks of treatment. Angiotensinogen was normalized to creatinine.
Measured: Baseline to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2016 (estimated)
- Study startMar 2016
- Primary completionAug 2019
- Study completionAug 2020
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 DiabetesStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tulane University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Dragana Lovre, MD, Principal investigator, Tulane University School of MedicineTina Thethi, MD, Principal investigator, AdventHealth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02796170
- Sponsor's protocol ID
- 812701
- Status last verified
- Oct 2022
- First submitted
- 26 Apr 2016
- Last updated
- 1 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibition of Urinary Angiotensinogen and the Reduction of Blood Pressure by SGLT2 Inhibition in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT02796170
- Acronym / sponsor ID
- 812701
- Conditions
- Type 2 Diabetes, Hypertension
- Keywords
- SGLT-2 inhibitor, urinary angiotensinogen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Tulane University School of MedicineUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Mar 2016 (actual)
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 10 Jun 2016 (estimated)
- Results
- Posted 1 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the effect of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on blood pressure and urinary angiotensinogen. This is a cross over study design, where 40 subjects will receive Dapagliflozin for 6 weeks followed by placebo for 6 weeks, or placebo for 6 weeks followed by Dapagliflozin for 6 weeks. In addition there will be an arm of 10 subjects who will receive sulfonylurea in an open label as a comparative to the cross over subjects to assess if the effect of Dapagliflozin may also be in part due to improved glycemic control.
Detailed description
Clinical trials of two SGLT2 inhibitors, canagliflozin and dapagliflozin, have reported drops in systolic blood pressure of ~5 mmHg. Inappropriate activation of intrarenal renin-angiotensin system (RAS) is a major contributor to the increased arterial pressure and tissue injury including diabetic nephropathy. A key factor in the intrarenal RAS activation is stimulation of intrarenal angiotensinogen (AGT) which is the precursor of angiotensin peptides. From previous studies, it has been shown that high blood sugars in patients with type1 and type 2 diabetes mellitus is accompanied by elevated intrarenal AGT and urinary AGT levels. High glucose results in stimulation of AGT production. The high glucose levels augments intrarenal AGT levels in diabetes mellitus leading to the development of high blood pressure and diabetic nephropathy.
The investigators propose to conduct a single-center randomized, double blind, cross over study of the effect of Dapagliflozin over 6 weeks, followed by placebo over 6 weeks on the other treatment allocation (those getting placebo first will cross over to Dapagliflozin and vice versa). Treatment will be stratified according to the underlying presence or absence of hypertension.
- Type 2 diabetes with hypertension and on renin-angiotensin-aldosterone system (RAAS) blocking drugs with stable blood pressure on therapy; n= 20
- Type 2 diabetes without hypertension and not on RAAS blocking drugs n=10
If unable to recruit 10 participants without hypertension the investigators will increase the number with hypertension for a total of 30. Stratification by hypertension status will remain and is important in understanding the effect of SGLT2 inhibition in patients not on BP lowering drugs.
In addition a Sulfonylurea (SU) arm will also be included - 10 participants who are on metformin and other background therapy (with the exclusion of SGLT-2 inhibitor and sulfonylurea) will be recruited. This will be an open-labeled arm. Participants will assessed at baseline. Participants will then receive usual care for 6 weeks. At the end of 6 weeks, participants will then undergo another assessment before being provided SU for 6 weeks. At the end of 6 weeks, participants will undergo assessment again. The aim is to determine whether any effects seen with Dapagliflozin are specific to that drug or related simply to improved glycemic control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Active comparator | Drug: Dapagliflozin, Drug: PlaceboParticipants underwent 6 weeks of Dapagliflozin or placebo (washout period for 2 weeks) and then crossed over to 6 weeks of placebo or Dapagliflozin. |
| Placebo | Active comparator | Drug: Dapagliflozin, Drug: PlaceboParticipants underwent 6 weeks of Dapagliflozin or placebo (washout period for 2 weeks) and then crossed over to 6 weeks of placebo or Dapagliflozin. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type 2 diabetes with hypertension and on RAAS blocking drugs OR
- Type 2 diabetes without hypertension and not on RAAS blocking drugs
- Hemoglobin A1c between 7% and 9% (inclusive)
- Estimated glomerular filtration rate (eGFR) ≥60 ml/min
- Capacity to understand and sign informed consent
Key exclusion criteria (10 listed)
- Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3x upper limit of normal (ULN)
- Total bilirubin >2.0 mg/dL
- Positive serologic evidence of current infectious liver disease, including Hepatitis B viral antibody immunoglobulin M (IGM), Hepatitis B surface antigen, and Hepatitis C virus antibody
- Estimated glomerular filtration rate (eGFR) <60 ml/min
- Recent cardiovascular events with the last 2 months: acute coronary syndrome (ACS), hospitalization for unstable angina or acute myocardial infarction, acute stroke or transient ischemic attack (TIA), or post coronary artery revascularization
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 |
|---|---|---|
| Dapagliflozin5mg pill taken once daily | Drug | Dapagliflozin, Placebo |
| Placebo5mg pill taken once daily- placebo of Dapagliflozin | Drug | Dapagliflozin, Placebo |
Primary outcome
Change in Blood Pressure From Baseline to 6 Weeks Measured by ABPM
Time frame: Baseline to 6 weeks
Blood pressure was measured at baseline with a 24 hour ambulatory blood pressure machine (ABPM), and again after 6 weeks of treatment.
1 secondary outcome
Change in Urinary AGT Levels From Baseline to 6 Weeks
Time frame: Baseline to 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Dragana Lovre, MD principal investigator
Tulane University School of Medicine
Tina Thethi, MD principal investigator
AdventHealth
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 and Hypertension, run by Tulane University School 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 5 inclusion and 10 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: finished, as of the sponsor's last update on 1 Nov 2022. 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. 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 1 Nov 2022). 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 Blood Pressure From Baseline to 6 Weeks Measured by ABPM (time frame: Baseline to 6 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 1 Nov 2022.