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

NCT03938389 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2018H0061K23DK117041
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PreDiabetes; Impaired Glucose Tolerance; Obesity; Blood Pressure

Keywords

African American; Black; Prediabetes; Impaired Glucose Tolerance

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Central Aortic Pressure (mmHg) from Baseline to 26 weeks

  26 weeks

Study Arms (3)

Valsartan

ACTIVE COMPARATOR

Valsartan 160 mg twice daily for 26 weeks

Drug: Valsartan 160mg

Sacubitril/Valsartan

EXPERIMENTAL

Sacubitril/Valsartan (97/103 mg) twice daily for 26 weeks

Drug: Sacubitril-Valsartan Tab 97-103 MG

Placebo

PLACEBO COMPARATOR

placebo (+/- amlodipine 2.5-5 mg twice daily if high blood pressure)

Drug: Placebo Oral Tablet

Interventions

Sacubitril-Valsartan Tab 97-103 MG DRUG

Participants will take Sacubitril-Valsartan for 26 weeks

Also known as: Entresto

Sacubitril/Valsartan

Valsartan 160mg DRUG

Participant will take Valsartan for 26 weeks

Also known as: Diovan

Valsartan

Placebo Oral Tablet DRUG

Participant with take placebo for 26 weeks or if blood pressure elevated will receive standard of care blood pressure medication, amlodipine.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ohio State University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance; Obesity

Interventions

sacubitril and valsartan sodium hydrate drug combination; Valsartan

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Joshua J Joseph, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Randomized prospective controlled clinical trial with three parallel arms, no crossover.

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 6, 2019
• Study Start: February 25, 2020
• Primary Completion: February 8, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)