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

Sponsor

Ohio State University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03938389

Collaborator

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

Enrollment

Location

Arms

41.2

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
PreDiabetes Impaired Glucose Tolerance Obesity Blood Pressure	Drug: Sacubitril-Valsartan Tab 97-103 MG Drug: Valsartan 160mg Drug: Placebo Oral Tablet	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Blinding

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 25, 2020

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.