The Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose in African Americans

The Role of the Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose Metabolism Among African Americans: Pilot Study

The primary objective is to examine the impact of the Renin-Angiotensin-Aldosterone System (RAAS) blockade with medications (valsartan) or RAAS and neprilysin inhibition (valsartan/sacubitril) vs. placebo on changes in blood sugar and insulin secretion from the pancreas over 26 weeks assessed with glucose clamp studies among African Americans (AAs) with impaired glucose tolerance.

The investigators hypothesize that combined RAAS/neprilysin inhibition will lead to greater improvement in insulin release from the pancreas and improved blood sugar compared to RAAS inhibition alone among AAs with impaired glucose tolerance.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; PreDiabetes; Blood Pressure; Impaired Glucose Tolerance
• Intervention / Treatment: Drug: Valsartan 160mg; Drug: Sacubitril-Valsartan Tab 97-103 MG; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amber Anaya, BS, CCRC; Phone Number: (614) 688-6257; Email: Amber.Anaya@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• African Americans aged 18-65 years old with a history of impaired fasting glucose, impaired glucose tolerance, hemoglobin A1c 5.7-6.4% or other risk factors for diabetes including metabolic syndrome, family history of type 2 diabetes in the parents or siblings or history of gestational diabetes will be invited to attend a formal screening visit. Participants with impaired glucose tolerance defined as 2-hour plasma glucose 140-199 mg/dl after a fasting 75-g oral glucose tolerance test and who meet other enrollment criteria will be enrolled.

Exclusion Criteria:

• Type 2 Diabetes (American Diabetes Association Criteria)
• Hypertension with systolic blood pressure (SBP) > 150 mmHg or diastolic blood pressure (DBP) > 100 mmHg or taking anti-hypertensive medications
• SBP < 100 mmHg or DBP < 60 mmHg
• Pharmacologic treatment with statins, β-Blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, and/or mineralocorticoid antagonists
• Steroid use
• Hyperkalemia (Potassium > 5.0 milliequivalent/L)
• Abnormal renal function tests: Glomerular Filtration Rate calculated using the Chronic Kidney Disease Epidemiology Equation < 60 ml/min/1.73 m²
• Treatment with oral hypoglycemic medications,
• Use of antipsychotic medications or severe psychiatric disorders (severe mental illness)

Severe Psychiatric Disorders:

• Schizophrenia
• Paranoid and other psychotic disorders
• Bipolar disorders (hypomanic, manic, depressive, and mixed)
• Major depressive disorders (single episode or recurrent)
• Schizoaffective disorders (bipolar or depressive)
• Pervasive developmental disorders
• Obsessive-compulsive disorders
• Depression in childhood and adolescence
• Panic disorder
• Post-traumatic stress disorders (acute, chronic, or with delayed onset)
• Bulimia Nervosa

• Anorexia Nervosa

  • History of, or planned, bariatric surgery,
  • Weight loss > 5% over the previous 6 months,
  • Pregnancy, planning to conceive a child in the next 9 months, or progesterone based contraception and unable to switch to non-progesterone based contraception,
  • Previous or current diagnosis of cardiac structural and functional abnormalities, history or current diagnosis of heart failure (New York Heart Association classes II-IV), history of myocardial infarction, coronary bypass surgery, or percutaneous coronary intervention during the 6 months prior to screening,
  • History of angioedema, or known hypersensitivity to study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Valsartan; Valsartan 160 mg twice daily for 26 weeks	Drug: Valsartan 160mg; Participant will take Valsartan for 26 weeks; Other Names: Diovan
Experimental: Sacubitril/Valsartan; Sacubitril/Valsartan (97/103 mg) twice daily for 26 weeks	Drug: Sacubitril-Valsartan Tab 97-103 MG; Participants will take Sacubitril-Valsartan for 26 weeks; Other Names: Entresto
Placebo Comparator: Placebo; placebo (+/- amlodipine 2.5-5 mg twice daily if high blood pressure)	Drug: Placebo Oral Tablet; Participant with take placebo for 26 weeks or if blood pressure elevated will receive standard of care blood pressure medication, amlodipine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to 26 weeks in β-cell function (first-phase insulin secretion)	β-cell function will be assessed by first-phase insulin secretion, calculated as the mean insulin concentration (uIU/mL) over 10 minutes during the hyperglycemic clamp.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Central Aortic Pressure (mmHg) from Baseline to 26 weeks	Central Aortic Pressure, measured via a non-invasive method using the SphygmoCor XCEL device, in mmHg.	26 weeks

Collaborators and Investigators

• Sponsor: Ohio State University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Joshua J Joseph, MD, The Ohio State University Wexner Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 1, 2019
• First Submitted That Met QC Criteria: May 3, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Prediabetes; African American; Impaired Glucose Tolerance; Black
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: 2018H0061; K23DK117041 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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