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

NCT ID: NCT03938389

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-25
• Study Completion Date: 2026-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Valsartan

Valsartan 160 mg twice daily for 26 weeks

Group Type: ACTIVE_COMPARATOR

Valsartan 160mg

Intervention Type: DRUG

Participant will take Valsartan for 26 weeks

Sacubitril/Valsartan

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

Group Type: EXPERIMENTAL

Sacubitril-Valsartan Tab 97-103 MG

Intervention Type: DRUG

Participants will take Sacubitril-Valsartan for 26 weeks

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

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

Interventions

Sacubitril-Valsartan Tab 97-103 MG

Participants will take Sacubitril-Valsartan for 26 weeks

Intervention Type: DRUG

Valsartan 160mg

Participant will take Valsartan for 26 weeks

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Entresto; Diovan

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Joshua Joseph, MD

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua J Joseph, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

K23DK117041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2018H0061

Identifier Type: -

Identifier Source: org_study_id