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Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk

Primary Purpose

Prediabetes

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Glucose
Glucose with Non-fat Milk
Glucose with Whey Protein Isolate
Glucose with Sodium Caseinate
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 Dairy, Milk, Glucose, Postprandial, Hyperglycemia, Prediabetes, Blood glucose, Oxidative stress, Vascular health, Vascular function

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. hemoglobin A1c 5.7-6.4%
  2. non-dietary supplement user
  3. no medications affecting vasodilation, inflammation, or energy metabolism
  4. no CVD
  5. nonsmokers
  6. individuals having blood pressure <140/90 mmHg and total cholesterol <240 mg/dL

Exclusion Criteria:

  1. unstable weight (±2 kg)
  2. vegetarian or dairy allergy
  3. alcohol intake >3 drinks/day or >10 drinks/week
  4. ≥7 hours/week of aerobic activity

Sites / Locations

  • The Ohio State University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Glucose

Glucose with Non-fat Milk

Glucose with Whey Protein Isolate

Glucose with Sodium Caseinate

Arm Description

This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.

This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.

This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.

This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.

Outcomes

Primary Outcome Measures

Vascular Endothelial Function
Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline)

Secondary Outcome Measures

Nitrite/Nitrate (NOx)
NOx AUC for 0-180 minutes
Plasma Glucose
Plasma glucose concentration from 0-180 minutes
Malondialdehyde (MDA)
Plasma MDA measured as MDA AUC from 0-180 minutes
Arginine (ARG)
Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes
Asymmetric Dimethylarginine/Arginine (ADMA/ARG)
Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes
Symmetric Dimethylarginine/Arginine (SDMA/ARG)
Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes
Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2)
Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes
Insulin
Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes
Cholecystokinin (CCK)
Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes
8-isoprostaglandin-F2a
Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes
8-isoprostaglandin-F2a/Arachidonic Acid
Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes
Arachidonic Acid
Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes

Full Information

First Posted
June 24, 2015
Last Updated
May 4, 2019
Sponsor
Ohio State University
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1. Study Identification

Unique Protocol Identification Number
NCT02482675
Brief Title
Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk
Official Title
Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
June 2015 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
February 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Cardiovascular disease (CVD) is the leading cause of death in the United States. Short-term increases in blood sugar, or postprandial hyperglycemia (PPH), affect blood vessel function and increase the risk of CVD. Greater intakes of dairy foods have been associated with a lower risk of CVD, but whether these effects occur directly or indirectly by displacing foods in the diet that might increase CVD risk is unclear. The health benefits of dairy on heart health are at least partly attributed to its ability to limit PPH and resulting PPH-mediated responses leading to vascular dysfunction. This provides rationale to further investigate dairy as a dietary strategy to reduce PPH and risk for CVD. The objective of this study is to define the extent to which dairy milk, and its whey and casein protein fractions, protect against postprandial vascular dysfunction by reducing oxidative stress responses that limit nitric oxide bioavailability to the vascular endothelium in adults with prediabetes.
Detailed Description
This study consists of four, 3-hour postprandial trials in response to consuming the following dietary treatments: 1. oral glucose challenge, 2. oral glucose challenge in combination with non-fat milk, 3. oral glucose challenge in combination with whey protein isolate, and 4. oral glucose challenge in combination with sodium caseinate. For three days preceding each trial, participants will be provided all meals to standardize physiologic responses to test meals. On each trial day, vascular function will be assessed and blood samples collected prior to and at 30 minute intervals for 3 hours following test meal ingestion.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prediabetes
Keywords
Dairy, Milk, Glucose, Postprandial, Hyperglycemia, Prediabetes, Blood glucose, Oxidative stress, Vascular health, Vascular function

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Glucose
Arm Type
Active Comparator
Arm Description
This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.
Arm Title
Glucose with Non-fat Milk
Arm Type
Experimental
Arm Description
This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.
Arm Title
Glucose with Whey Protein Isolate
Arm Type
Experimental
Arm Description
This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.
Arm Title
Glucose with Sodium Caseinate
Arm Type
Experimental
Arm Description
This study day will last approximately three hours and will be separated from the other arms by four days for men and one month for women.
Intervention Type
Other
Intervention Name(s)
Glucose
Intervention Description
Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.
Intervention Type
Other
Intervention Name(s)
Glucose with Non-fat Milk
Intervention Description
Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.
Intervention Type
Other
Intervention Name(s)
Glucose with Whey Protein Isolate
Intervention Description
Following baseline measurements, participants will consume 75 g glucose and whey protein isolate dissolved in 2 cups water within five minutes.
Intervention Type
Other
Intervention Name(s)
Glucose with Sodium Caseinate
Intervention Description
Following baseline measurements, participants will consume 75 g glucose and sodium caseinate dissolved in 2 cups water within five minutes.
Primary Outcome Measure Information:
Title
Vascular Endothelial Function
Description
Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline)
Time Frame
Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)
Secondary Outcome Measure Information:
Title
Nitrite/Nitrate (NOx)
Description
NOx AUC for 0-180 minutes
Time Frame
Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline)
Title
Plasma Glucose
Description
Plasma glucose concentration from 0-180 minutes
Time Frame
Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline)
Title
Malondialdehyde (MDA)
Description
Plasma MDA measured as MDA AUC from 0-180 minutes
Time Frame
Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline)
Title
Arginine (ARG)
Description
Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes
Time Frame
ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
Asymmetric Dimethylarginine/Arginine (ADMA/ARG)
Description
Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes
Time Frame
ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
Symmetric Dimethylarginine/Arginine (SDMA/ARG)
Description
Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes
Time Frame
SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2)
Description
Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes
Time Frame
Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
Insulin
Description
Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes
Time Frame
Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
Cholecystokinin (CCK)
Description
Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes
Time Frame
CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
8-isoprostaglandin-F2a
Description
Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes
Time Frame
8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
8-isoprostaglandin-F2a/Arachidonic Acid
Description
Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes
Time Frame
8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Title
Arachidonic Acid
Description
Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes
Time Frame
Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: hemoglobin A1c 5.7-6.4% non-dietary supplement user no medications affecting vasodilation, inflammation, or energy metabolism no CVD nonsmokers individuals having blood pressure <140/90 mmHg and total cholesterol <240 mg/dL Exclusion Criteria: unstable weight (±2 kg) vegetarian or dairy allergy alcohol intake >3 drinks/day or >10 drinks/week ≥7 hours/week of aerobic activity
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard S Bruno, PhD, RD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25520374
Citation
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27;131(4):e29-322. doi: 10.1161/CIR.0000000000000152. Epub 2014 Dec 17. No abstract available. Erratum In: Circulation. 2015 Jun 16;131(24):e535. Circulation. 2016 Feb 23;133(8):e417.
Results Reference
background
PubMed Identifier
11176766
Citation
DECODE Study Group, the European Diabetes Epidemiology Group.. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001 Feb 12;161(3):397-405. doi: 10.1001/archinte.161.3.397.
Results Reference
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PubMed Identifier
26024056
Citation
Ballard KD, Bruno RS. Protective role of dairy and its constituents on vascular function independent of blood pressure-lowering activities. Nutr Rev. 2015 Jan;73(1):36-50. doi: 10.1093/nutrit/nuu013.
Results Reference
background
PubMed Identifier
23966328
Citation
Ballard KD, Mah E, Guo Y, Pei R, Volek JS, Bruno RS. Low-fat milk ingestion prevents postprandial hyperglycemia-mediated impairments in vascular endothelial function in obese individuals with metabolic syndrome. J Nutr. 2013 Oct;143(10):1602-10. doi: 10.3945/jn.113.179465. Epub 2013 Aug 21.
Results Reference
background
PubMed Identifier
30412905
Citation
McDonald JD, Mah E, Chitchumroonchokchai C, Dey P, Labyk AN, Villamena FA, Volek JS, Bruno RS. Dairy milk proteins attenuate hyperglycemia-induced impairments in vascular endothelial function in adults with prediabetes by limiting increases in glycemia and oxidative stress that reduce nitric oxide bioavailability. J Nutr Biochem. 2019 Jan;63:165-176. doi: 10.1016/j.jnutbio.2018.09.018. Epub 2018 Sep 25.
Results Reference
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Regulation of Postprandial Nitric Oxide Bioavailability and Vascular Function By Dairy Milk

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