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

Phase 4

Active, not recruiting

• Conditions: Impaired Glucose Tolerance; PreDiabetes; Obesity; Blood Pressure
• Interventions: Drug: Valsartan 160mg; Drug: Sacubitril-Valsartan Tab 97-103 MG; Drug: Placebo Oral Tablet

• Registration Number: NCT03938389
• Lead Sponsor: Ohio State University

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-05-01
• Study First Submitted QC: 2019-05-03
• Study First Posted: 2019-05-06
• Study Start: 2020-02-25
• Primary Completion: 2024-02-08
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-01
• Last Update Posted: 2024-08-05
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Valsartan	Valsartan 160mg	Valsartan 160 mg twice daily for 26 weeks
Sacubitril/Valsartan	Sacubitril-Valsartan Tab 97-103 MG	Sacubitril/Valsartan (97/103 mg) twice daily for 26 weeks
Placebo	Placebo Oral Tablet	placebo (+/- amlodipine 2.5-5 mg twice daily if high blood pressure)

Primary Outcome Measures

Name	Time	Method
Change from Baseline to 26 weeks in β-cell function (first-phase insulin secretion)	26 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States