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

Primary Purpose

PreDiabetes, Impaired Glucose Tolerance, Obesity

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sacubitril-Valsartan Tab 97-103 MG
Valsartan 160mg
Placebo Oral Tablet
Sponsored by
Ohio State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for PreDiabetes focused on measuring African American, Black, Prediabetes, Impaired Glucose Tolerance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • The Ohio State University Wexner Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Placebo Comparator

Arm Label

Valsartan

Sacubitril/Valsartan

Placebo

Arm Description

Valsartan 160 mg twice daily for 26 weeks

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
May 1, 2019
Last Updated
August 10, 2023
Sponsor
Ohio State University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03938389
Brief Title
The Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose in African Americans
Official Title
The Role of the Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose Metabolism Among African Americans: Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 25, 2020 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PreDiabetes, Impaired Glucose Tolerance, Obesity, Blood Pressure
Keywords
African American, Black, Prediabetes, Impaired Glucose Tolerance

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized prospective controlled clinical trial with three parallel arms, no crossover.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Blinding
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Valsartan
Arm Type
Active Comparator
Arm Description
Valsartan 160 mg twice daily for 26 weeks
Arm Title
Sacubitril/Valsartan
Arm Type
Experimental
Arm Description
Sacubitril/Valsartan (97/103 mg) twice daily for 26 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo (+/- amlodipine 2.5-5 mg twice daily if high blood pressure)
Intervention Type
Drug
Intervention Name(s)
Sacubitril-Valsartan Tab 97-103 MG
Other Intervention Name(s)
Entresto
Intervention Description
Participants will take Sacubitril-Valsartan for 26 weeks
Intervention Type
Drug
Intervention Name(s)
Valsartan 160mg
Other Intervention Name(s)
Diovan
Intervention Description
Participant will take Valsartan for 26 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Participant with take placebo for 26 weeks or if blood pressure elevated will receive standard of care blood pressure medication, amlodipine.
Primary Outcome Measure Information:
Title
Change from Baseline to 26 weeks in β-cell function (first-phase insulin secretion)
Description
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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Change in Central Aortic Pressure (mmHg) from Baseline to 26 weeks
Description
Central Aortic Pressure, measured via a non-invasive method using the SphygmoCor XCEL device, in mmHg.
Time Frame
26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua J Joseph, MD
Organizational Affiliation
The Ohio State University Wexner Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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