Clinical trial NCT06843902: Improving Coronary Vascular Health in Women
Official title: ImproviNg Coronary Vascular Health in Women With Risk Factors fOR Myocardial Infarction Type 2 (INFORM-2)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HIV-1-infection
Coronary Microvascular Dysfunction
Metabolic Disease
Keywords: HIV
women
diabetes
chronic kidney disease
SGLT2 inhibitor therapy
coronary flow reserve
cardiovascular disease prevention
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2025-02-25
Enrollment: 80
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Women with HIV have an increased risk of having a myocardial infarction (heart attack) as compared to women without HIV. One of the mechanisms underlying the increased risk of myocardial infarction among women with HIV may involve reduced ability to increase blood flow through large and small coronary arteries at times when increased flow of oxygen-carrying blood is needed. We are conducting a study randomizing women with HIV and either diabetes, chronic kidney disease, or both to health education alone or to health education plus referral to see either an Endocrinologist or a Nephrologist in a subspecialty clinic for consideration of treatment with medication in a class known as sodium glucose transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors are clinically approved for use in patients with diabetes or chronic kidney disease but have been shown to be underutilized in people with HIV. One of our key analytic aims will be to test if SGLT2 inhibitor therapy results in improved blood flow through the large and small coronary arteries among women with HIV and either diabetes, chronic kidney disease, or both but who have no history of myocardial infarction. A second aim will be to test if subspecialty clinic referral (with or without SGLT2 inhibitor therapy prescription) results in improved blood flow through the large and small coronary arteries among the same group.

Detailed description: Women with HIV have an increased risk of having a myocardial infarction (heart attack) as compared to women without HIV. One of the mechanisms underlying the increased risk of myocardial infarction among women with HIV may involve reduced ability to increase blood flow through large and small coronary arteries at times when increased flow of oxygen-carrying blood is needed. We are conducting a study randomizing women with HIV and either diabetes, chronic kidney disease, or both to health education alone or to health education plus referral to see either an Endocrinologist or a Nephrologist in a subspecialty clinic for consideration of treatment with medication in a class known as sodium glucose transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors are clinically approved for use in patients with diabetes or chronic kidney disease but have been shown to be underutilized in people with HIV. Prior to randomization, to confirm eligibility, participants will have undergone history, physical, lab tests, and cardiac positron emission tomography/computed tomography (PET/CT) scanning to confirm that there is a measure of impairment in stimulated blood flow through the large and small arteries of the heart. Randomized participants in both groups will be followed for 6 months and then will undergo repeat history, physical, laboratory testing, and repeat cardiac PET/CT scanning. One of our key analytic aims will be to test if SGLT2 inhibitor therapy results in improved blood flow through the large and small coronary arteries among women with HIV and either diabetes, chronic kidney disease, or both but who have no history of myocardial infarction. A second aim will be to test if subspecialty clinic referral (with or without SGLT2 inhibitor therapy prescription) results in improved blood flow through the large and small coronary arteries among the same group. We will also investigate effects of SGLT inhibitor therapy (and, separately, of subspecialty clinic referral) on fat tissue around the heart, as well as on blood and urine-based markers of metabolic disease and inflammation.

Eligibility criteria: Inclusion Criteria:

* female sex-at-birth
* self-report of HIV on stable anitretroviral therapy ≥180 days
* age 45 -75 years
* at least 1 of the following 3 conditions: i) type 2 diabetes mellitus ii) estimated glomerular filtration rate 30-60 ml/min/1.73 m2 iii) urine albumin to creatinine ratio \>30 mg/g
* coronary flow reserve \<2.5 on screening cardiac positron emission tomography/computed tomography

Exclusion Criteria:

* current SGLT2 inhibitor use
* known allergy to SGLT2 inhibitor use
* type 1 diabetes or ketoacidosis prone diabetes (diabetes with a history of ketoacidosis)
* self-reported history of polycystic kidney disease
* self-reported history of myocardial infarction, stroke, or coronary revascularization
* stable or unstable angina
* self-reported history of heart failure
* hemoglobin A1c ≥8.5% at screen
* uncontrolled hypertension at screen, defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg
* estimated glomerular filtration rate \<30 ml/min/1.73 m2
* currently receiving hemodialysis or peritoneal dialysis
* CD4 \<400 cell/mm3
* current treatment with systemic (oral, IV, IM or intra-articular) steroids or anti-inflammatory/immune suppressant therapies (excluding topical therapies, UV therapy, ASA-derivatives, or NSAIDs) for any indication, including kidney disease
* pregnancy or breastfeeding
* known allergy to 13N Ammonia/82Rubidium or to Regadenoson/Adenosine
* concurrent enrollment in conflicting research study

Primary outcomes:
measure: Coronary Flow Reserve
timeFrame: 24 weeks
measure: Ectopic Adipose Tissue
timeFrame: 24 weeks
Secondary outcomes:
measure: Kidney-related biomarkers
timeFrame: 24 weeks
measure: Metabolic biomarkers
timeFrame: 24 weeks
measure: Immune/inflammatory biomarkers
timeFrame: 24 weeks
measure: HIV-specific parameters
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: MGH/HMS
name: Markella V Zanni, MD
role: PRINCIPAL_INVESTIGATOR
References: