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出境医 / 临床实验 / The Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose in African Americans

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

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
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
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 : February 25, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : December 2022
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 Name: 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 Name: 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 :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

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

Locations
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United States, Ohio
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Amber Anaya, BS, CCRCLPN    614-688-6257    Amber.Anaya@osumc.edu   
Principal Investigator: Joshua J Joseph, MD         
Sponsors and Collaborators
Ohio State University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Joshua J Joseph, MD The Ohio State University Wexner Medical Center
Tracking Information
First Submitted Date  ICMJE May 1, 2019
First Posted Date  ICMJE May 6, 2019
Last Update Posted Date March 3, 2021
Actual Study Start Date  ICMJE February 25, 2020
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Renin-Angiotensin-Aldosterone System in Adiposity, Blood Pressure and Glucose in African Americans
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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  ICMJE
  • PreDiabetes
  • Impaired Glucose Tolerance
  • Obesity
  • Blood Pressure
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2019) 		90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amber Anaya, BS, CCRC (614) 688-6257 Amber.Anaya@osumc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03938389
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Joshua Joseph, MD, Ohio State University
Study Sponsor  ICMJE Ohio State University
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Joshua J Joseph, MD The Ohio State University Wexner Medical Center
PRS Account Ohio State University
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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