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

• ClinicalTrials.gov Identifier: NCT03938389
• Recruitment Status: Recruiting
• First Posted: May 6, 2019
• Last Update Posted: February 20, 2020
• Sponsor: Ohio State University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Joshua Joseph, MD, Ohio State University

Tracking Information

• First Submitted Date: May 1, 2019
• First Posted Date: May 6, 2019
• Last Update Posted Date: February 20, 2020
• Estimated Study Start Date: February 25, 2020
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2019)

Change from Baseline to 26 weeks in β-cell function (first-phase insulin secretion) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 3, 2019)

Change in Central Aortic Pressure (mmHg) from Baseline to 26 weeks [ Time Frame: 26 weeks ]

Central Aortic Pressure, measured via a non-invasive method using the SphygmoCor XCEL device, in mmHg.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Blinding

Primary Purpose: Prevention

Condition

• PreDiabetes
• Impaired Glucose Tolerance
• Obesity
• Blood Pressure

Intervention

• Drug: Sacubitril-Valsartan Tab 97-103 MG
  Participants will take Sacubitril-Valsartan for 26 weeks
  Other Name: Entresto
• Drug: Valsartan 160mg
  Participant will take Valsartan for 26 weeks
  Other Name: Diovan
• 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.

Study Arms

• Active Comparator: Valsartan
  Valsartan 160 mg twice daily for 26 weeks
  Intervention: Drug: Valsartan 160mg
• Experimental: Sacubitril/Valsartan
  Sacubitril/Valsartan (97/103 mg) twice daily for 26 weeks
  Intervention: Drug: Sacubitril-Valsartan Tab 97-103 MG
• Placebo Comparator: Placebo
  placebo (+/- amlodipine 2.5-5 mg twice daily if high blood pressure)
  Intervention: Drug: Placebo Oral Tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 3, 2019): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2021
• Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amber Anaya, BS, CCRC; (614) 688-6257; Amber.Anaya@osumc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03938389
• Other Study ID Numbers: 2018H0061; K23DK117041 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Joshua Joseph, MD, Ohio State University
• Study Sponsor: Ohio State University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Joshua J Joseph, MD; The Ohio State University Wexner Medical Center

• PRS Account: Ohio State University
• Verification Date: February 2020