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Assessment of Dapagliflozin on Vascular Health in Patients With Type 2 Diabetes (SFRNDM2)

Primary Purpose

Diabetes Mellitus, Type 2, Endothelial Dysfunction

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dapagliflozin
Placebo
Sponsored by
Boston University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Mellitus, Type 2 focused on measuring Sodium-Glucose Cotransporter-2 (SGLT2) inhibitor, Dapagliflozin, Endothelial cell (EC) Health, Vascular function, EC gene expression levels, Circulating miRNA, Biomarkers

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of T2DM for minimum of 3 months defined as fasting glucose greater than or equal to 120 mg/dL, hemoglobin A1C (HbA1C) ≥6.5%
  • Body mass index (BMI) >25
  • Willing to give written informed consent and able to understand, to participate in and to comply with the study requirements.

Exclusion Criteria:

  • Treatment with anticoagulation
  • Treatment with SGLT-2 inhibitor
  • HbA1c >9.5% within the last 3 months
  • Systolic blood pressure less than 120mm Hg
  • History of genital mycotic infections: more than one genital mycotic infection in the past two years
  • History of recurrent urinary tract infections: history of chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year)
  • History of allergy to SGLT-2 inhibitor
  • History of bladder cancer or prior pelvic radiation
  • More than one hypoglycemic events in the past 6 months and/or HbA1c <7.0%
  • Women lactating or pregnant. All women with childbearing potential will undergo a blood pregnancy test at each visit to exclude pregnancy.
  • Treatment with an investigational product within the last 30 days.
  • Clinically evident major illness of other organ systems, including clinically evident cancer, renal failure (GFR<60 mL/min), or other conditions that in the opinion of the principal investigator make a clinical study inappropriate

Sites / Locations

  • BU School of Medicine Evans 748Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dapagliflozin then Placebo

Placebo then dapagliflozin

Arm Description

Participants in this arm will receive dapagliflozin and then placebo with a 2 week wash out period in between.

Participants in this arm will receive placebo and then dapagliflozin with a 2 week wash out period in between.

Outcomes

Primary Outcome Measures

Insulin-mediated endothelial nitric oxide synthase (eNOS) phosphorylation measured in endothelial cells (ECs) at 6 weeks
The percentage change in the phosphorylation of eNOS is measured using quantitative immunofluorescence microscopy in EC collected before and after each treatment period.
Insulin-mediated endothelial nitric oxide synthase (eNOS) phosphorylation measured in endothelial cells (ECs) at 14 weeks
The percentage change in the phosphorylation of eNOS is measured using quantitative immunofluorescence microscopy in EC collected before and after each treatment period.

Secondary Outcome Measures

Flow-mediated dilation of the brachial artery at 6 weeks
The percentage change in the diameter of the brachial artery will be measured before and after a 5 minute cuff occlusion on the arm as a measure of endothelial cell (EC) function.
Flow-mediated dilation of the brachial artery at 14 weeks
The percentage change in the diameter of the brachial artery will be measured before and after a 5 minute cuff occlusion on the arm as a measure of endothelial cell (EC) function.
Arterial stiffness at 6 weeks
Arterial stiffness/compliance of the central aorta and upper extremity will be assessed by measuring carotid-femoral and carotid-radial pulse wave velocity (PWV). A small probe is used to record signals from the carotid, radial, and femoral arteries.
Arterial stiffness at 14weeks
Arterial stiffness/compliance of the central aorta and upper extremity will be assessed by measuring carotid-femoral and carotid-radial pulse wave velocity (PWV). A small probe is used to record signals from the carotid, radial, and femoral arteries.
Microvascular dilator function by EndoPAT at 6 weeks
EndoPAT is a noninvasive test to measure the amount of blood flow through the arteries. It determines if the artery is healthy.
Microvascular dilator function by EndoPAT at 14 weeks
EndoPAT is a noninvasive test to measure the amount of blood flow through the arteries. It determines if the artery is healthy.
Plasma non-coding RNA (ncRNA) measurement at 6 weeks
Non-coding RNAs (ncRNAs) levels will be assessed using quantitative polymerase chain reaction (PCR) of RNA isolated from plasma.
Plasma non-coding RNA (ncRNA) measurement at 14 weeks
Non-coding RNAs (ncRNAs) levels will be assessed using quantitative PCR of RNA isolated from plasma.
EC measures of noncoding RNA at 6 weeks
Non-coding RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
EC measures of noncoding RNA at 14 weeks
Non-coding RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
EC measures of coding RNA at 6 weeks
RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
EC measures of coding RNA at 14 weeks
RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
Circulating brain natriuretic peptide (BNP) biomarkers of vascular health at 6 weeks
A BNP result greater than 100 pg/mL is abnormal.
Circulating brain natriuretic peptide (BNP) biomarkers of vascular health at 14 weeks
A BNP result greater than 100 pg/mL is abnormal.
Circulating C-reactive protein (CRP) biomarkers of vascular health at 6 weeks
Normal CRP is <10 mg/L. Results 10 or greater are considered abnormal.
Circulating C-reactive protein (CRP) biomarkers of vascular health at 14 weeks
Normal CRP is <10 mg/L. Results 10 or greater are considered abnormal.

Full Information

First Posted
November 19, 2021
Last Updated
May 25, 2023
Sponsor
Boston University
Collaborators
American Heart Association
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1. Study Identification

Unique Protocol Identification Number
NCT05139914
Brief Title
Assessment of Dapagliflozin on Vascular Health in Patients With Type 2 Diabetes
Acronym
SFRNDM2
Official Title
Assessment of Dapagliflozin on Vascular Health in Patients With Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston University
Collaborators
American Heart Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients with Type 2 Diabetes Mellitus (T2DM) have changes in blood vessel health that can lead to a higher chance of developing heart attacks or strokes. New medications for T2DM including dapagliflozin, which is a Sodium-Glucose Cotransporter-2 inhibitor (SGLT2) inhibitor, may help protect the heart and blood vessels. The overarching objective of this mechanistic study is to learn how a Sodium-Glucose Cotransporter-2 (SGT2) inhibitor, dapagliflozin, impacts vascular health in patients with Type 2 Diabetes Mellitus (T2DM). The investigators will compare the changes in vascular health to changes in endothelial cell (EC) phenotype including non-coding RNA (ncRNA) to develop evidence supporting the mechanism of cardiovascular benefit of SGLT2 inhibitors. This study will provide novel information regarding the mechanism of effects of novel treatments for endothelial function and vascular health in patients with T2DM to reduce cardiovascular (CV) risk. The research aims to assess the: effects of dapagliflozin on EC phenotype. impact of dapagliflozin on vasodilator function and additional measures of vascular health including arterial stiffness and circulating markers of vascular health.
Detailed Description
The study design is a two-treatment, two-period crossover, double-blind, placebo-controlled design study to investigate the effect of the SGLT2 inhibitor, dapagliflozin, on EC phenotype, EC RNA levels, circulating microRNA (miRNA), and biomarkers in patients with T2DM. Subjects will be randomized to treatment order in a 1:1 ratio to receive SGLT2 inhibitor (dapagliflozin) and then placebo or vice versa in a crossover design. Total study period for each study subject is 14 weeks consisting of: two treatment periods (dapagliflozin and placebo) lasting 6 weeks each (12 weeks total) and a 2 week washout period between treatment periods. Each subject undergoes a washout period of 2 weeks after completing first 6 weeks of treatment with either placebo or dapagliflozin. This is followed by crossover to the alternate treatment period of 6 weeks with dapagliflozin or placebo depending on their first treatment. Randomization will be done in block sizes of 2 or 4. Once assigned to treatment, participants will receive dapagliflozin 10 mg/day or placebo for 6 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Endothelial Dysfunction
Keywords
Sodium-Glucose Cotransporter-2 (SGLT2) inhibitor, Dapagliflozin, Endothelial cell (EC) Health, Vascular function, EC gene expression levels, Circulating miRNA, Biomarkers

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dapagliflozin then Placebo
Arm Type
Experimental
Arm Description
Participants in this arm will receive dapagliflozin and then placebo with a 2 week wash out period in between.
Arm Title
Placebo then dapagliflozin
Arm Type
Placebo Comparator
Arm Description
Participants in this arm will receive placebo and then dapagliflozin with a 2 week wash out period in between.
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Other Intervention Name(s)
Sodium-Glucose Cotransporter-2 (SGLT2) inhibitor
Intervention Description
10 mg/day (in capsule form) of dapagliflozin for 6 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo capsule for 6 weeks
Primary Outcome Measure Information:
Title
Insulin-mediated endothelial nitric oxide synthase (eNOS) phosphorylation measured in endothelial cells (ECs) at 6 weeks
Description
The percentage change in the phosphorylation of eNOS is measured using quantitative immunofluorescence microscopy in EC collected before and after each treatment period.
Time Frame
6 weeks
Title
Insulin-mediated endothelial nitric oxide synthase (eNOS) phosphorylation measured in endothelial cells (ECs) at 14 weeks
Description
The percentage change in the phosphorylation of eNOS is measured using quantitative immunofluorescence microscopy in EC collected before and after each treatment period.
Time Frame
14 weeks
Secondary Outcome Measure Information:
Title
Flow-mediated dilation of the brachial artery at 6 weeks
Description
The percentage change in the diameter of the brachial artery will be measured before and after a 5 minute cuff occlusion on the arm as a measure of endothelial cell (EC) function.
Time Frame
6 weeks
Title
Flow-mediated dilation of the brachial artery at 14 weeks
Description
The percentage change in the diameter of the brachial artery will be measured before and after a 5 minute cuff occlusion on the arm as a measure of endothelial cell (EC) function.
Time Frame
14 weeks
Title
Arterial stiffness at 6 weeks
Description
Arterial stiffness/compliance of the central aorta and upper extremity will be assessed by measuring carotid-femoral and carotid-radial pulse wave velocity (PWV). A small probe is used to record signals from the carotid, radial, and femoral arteries.
Time Frame
6 weeks
Title
Arterial stiffness at 14weeks
Description
Arterial stiffness/compliance of the central aorta and upper extremity will be assessed by measuring carotid-femoral and carotid-radial pulse wave velocity (PWV). A small probe is used to record signals from the carotid, radial, and femoral arteries.
Time Frame
14 weeks
Title
Microvascular dilator function by EndoPAT at 6 weeks
Description
EndoPAT is a noninvasive test to measure the amount of blood flow through the arteries. It determines if the artery is healthy.
Time Frame
6 weeks
Title
Microvascular dilator function by EndoPAT at 14 weeks
Description
EndoPAT is a noninvasive test to measure the amount of blood flow through the arteries. It determines if the artery is healthy.
Time Frame
14 weeks
Title
Plasma non-coding RNA (ncRNA) measurement at 6 weeks
Description
Non-coding RNAs (ncRNAs) levels will be assessed using quantitative polymerase chain reaction (PCR) of RNA isolated from plasma.
Time Frame
6 weeks
Title
Plasma non-coding RNA (ncRNA) measurement at 14 weeks
Description
Non-coding RNAs (ncRNAs) levels will be assessed using quantitative PCR of RNA isolated from plasma.
Time Frame
14 weeks
Title
EC measures of noncoding RNA at 6 weeks
Description
Non-coding RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
Time Frame
6 weeks
Title
EC measures of noncoding RNA at 14 weeks
Description
Non-coding RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
Time Frame
14 weeks
Title
EC measures of coding RNA at 6 weeks
Description
RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
Time Frame
6 weeks
Title
EC measures of coding RNA at 14 weeks
Description
RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.
Time Frame
14 weeks
Title
Circulating brain natriuretic peptide (BNP) biomarkers of vascular health at 6 weeks
Description
A BNP result greater than 100 pg/mL is abnormal.
Time Frame
6 weeks
Title
Circulating brain natriuretic peptide (BNP) biomarkers of vascular health at 14 weeks
Description
A BNP result greater than 100 pg/mL is abnormal.
Time Frame
14 weeks
Title
Circulating C-reactive protein (CRP) biomarkers of vascular health at 6 weeks
Description
Normal CRP is <10 mg/L. Results 10 or greater are considered abnormal.
Time Frame
6 weeks
Title
Circulating C-reactive protein (CRP) biomarkers of vascular health at 14 weeks
Description
Normal CRP is <10 mg/L. Results 10 or greater are considered abnormal.
Time Frame
14 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of T2DM for minimum of 3 months defined as fasting glucose greater than or equal to 120 mg/dL, hemoglobin A1C (HbA1C) ≥6.5% Body mass index (BMI) >25 Willing to give written informed consent and able to understand, to participate in and to comply with the study requirements. Exclusion Criteria: Treatment with anticoagulation Treatment with SGLT-2 inhibitor HbA1c >9.5% within the last 3 months Systolic blood pressure less than 120mm Hg History of genital mycotic infections: more than one genital mycotic infection in the past two years History of recurrent urinary tract infections: history of chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year) History of allergy to SGLT-2 inhibitor History of bladder cancer or prior pelvic radiation More than one hypoglycemic events in the past 6 months and/or HbA1c <7.0% Women lactating or pregnant. All women with childbearing potential will undergo a blood pregnancy test at each visit to exclude pregnancy. Treatment with an investigational product within the last 30 days. Clinically evident major illness of other organ systems, including clinically evident cancer, renal failure (GFR<60 mL/min), or other conditions that in the opinion of the principal investigator make a clinical study inappropriate
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Naomi Hamburg, MD
Phone
(617) 638-7260
Email
nhamburg@bu.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Leili Behrooz, MD
Phone
(617) 638-7260
Email
leili.behrooz@bmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naomi M Hamburg, MD
Organizational Affiliation
BU School of Medicine, Cardiovascular Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
BU School of Medicine Evans 748
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naomi M Hamburg, MD
Phone
617-638-7260
Email
naomi.hamburg@bmc.org
First Name & Middle Initial & Last Name & Degree
Leili Behrooz, MD
Phone
(617) 638-7260
Email
leili.behrooz@bmc.org

12. IPD Sharing Statement

Plan to Share IPD
No

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Assessment of Dapagliflozin on Vascular Health in Patients With Type 2 Diabetes

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