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

Boston University

Status and phase: Enrolling; Phase 4

Conditions: Endothelial Dysfunction; Diabetes Mellitus, Type 2

Treatments: Drug: Dapagliflozin; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05139914

H-41648

20SFRN35120118 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

Dapagliflozin then Placebo

Experimental group

Description:

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

Treatment:

Other: Placebo

Drug: Dapagliflozin

Placebo then dapagliflozin

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo

Drug: Dapagliflozin