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

Diabetes Mellitus, Type 2 Clinical Trial

— SFRNDM2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05139914
• Other study ID #: H-41648
• Secondary ID: 20SFRN35120118
• Status: Recruiting
• Phase: Phase 4
• Start date: May 31, 2022
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Boston University
• Contact: Naomi Hamburg, MD
• Phone: (617) 638-7260
• Email: nhamburg[@]bu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Endothelial Dysfunction

Intervention

Drug:
• Dapagliflozin
10 mg/day (in capsule form) of dapagliflozin for 6 weeks

Other:
• Placebo
Placebo capsule for 6 weeks

Locations

Country	Name	City	State
United States	BU School of Medicine Evans 748	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston University	American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 weeks
Primary	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.	14 weeks
Secondary	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.	6 weeks
Secondary	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.	14 weeks
Secondary	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.	6 weeks
Secondary	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.	14 weeks
Secondary	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.	6 weeks
Secondary	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.	14 weeks
Secondary	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.	6 weeks
Secondary	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.	14 weeks
Secondary	EC measures of noncoding RNA at 6 weeks	Non-coding RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.	6 weeks
Secondary	EC measures of noncoding RNA at 14 weeks	Non-coding RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.	14 weeks
Secondary	EC measures of coding RNA at 6 weeks	RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.	6 weeks
Secondary	EC measures of coding RNA at 14 weeks	RNA levels will be assessed using quantitative PCR of RNA isolated from endothelial cells.	14 weeks
Secondary	Circulating brain natriuretic peptide (BNP) biomarkers of vascular health at 6 weeks	A BNP result greater than 100 pg/mL is abnormal.	6 weeks
Secondary	Circulating brain natriuretic peptide (BNP) biomarkers of vascular health at 14 weeks	A BNP result greater than 100 pg/mL is abnormal.	14 weeks
Secondary	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.	6 weeks
Secondary	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.	14 weeks