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

May 4, 2019 updated by: Richard Bruno, Ohio State University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
23

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Glucose
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.
Other: Glucose
Following baseline measurements, participants will consume a 75 g glucose solution within five minutes.
Experimental: Glucose with Non-fat Milk
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.
Other: Glucose with Non-fat Milk
Following baseline measurements, participants will consume 75 g glucose dissolved in two cups of non-fat milk within five minutes.
Experimental: Glucose with Whey Protein Isolate
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.
Other: Glucose with Whey Protein Isolate
Following baseline measurements, participants will consume 75 g glucose and whey protein isolate dissolved in 2 cups water within five minutes.
Experimental: Glucose with Sodium Caseinate
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.
Other: Glucose with Sodium Caseinate
Following baseline measurements, participants will consume 75 g glucose and sodium caseinate dissolved in 2 cups water within five minutes.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Vascular Endothelial Function
Time Frame: Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)
Flow mediated dilation (FMD) of the brachial artery, calculated as FMD AUC for 0-180 minutes (change from baseline)
Area under curve for FMD for three hours (0, 30, 60, 90, 120, 180 minutes)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Nitrite/Nitrate (NOx)
Time Frame: Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline)
NOx AUC for 0-180 minutes
Area under curve for nitrite/nitrate for three hours (0, 30, 60, 90, 120, 180 min) (change from baseline)
Plasma Glucose
Time Frame: Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline)
Plasma glucose concentration from 0-180 minutes
Area under the curve for glucose for three hours (0, 30, 60, 90, 120, 180 minutes) (change from baseline)
Malondialdehyde (MDA)
Time Frame: Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline)
Plasma MDA measured as MDA AUC from 0-180 minutes
Area under curve for MDA for three hours (0, 30, 60, 90, 120, 150, 180 min.) (change from baseline)
Arginine (ARG)
Time Frame: ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma arginine concentration, calculated as ARG AUC from 0-180 minutes
ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Asymmetric Dimethylarginine/Arginine (ADMA/ARG)
Time Frame: ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma ADMA/arginine concentration, calculated as ADMA/ARG AUC from 0-180 minutes
ADMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Symmetric Dimethylarginine/Arginine (SDMA/ARG)
Time Frame: SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma SDMA/arginine concentration, calculated as SDMA/ARG AUC from 0-180 minutes
SDMA/ARG area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Tetrahydrobiopterin/Dihydrobiopterin (BH4/BH2)
Time Frame: Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma BH4/BH2 concentration, calculated as BH4/BH2 AUC from 0-180 minutes
Plasma BH4/BH2 concentration area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Insulin
Time Frame: Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma insulin concentration, calculated as insulin AUC from 0-180 minutes
Insulin area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Cholecystokinin (CCK)
Time Frame: CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma CCK concentration, calculated as CCK AUC from 0-180 minutes
CCK area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
8-isoprostaglandin-F2a
Time Frame: 8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Plasma 8-isoprostaglandin-F2a concentration, calculated as 8-isoprostaglandin-F2a AUC from 0-180 minutes
8-isoprostaglandin-F2a area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
8-isoprostaglandin-F2a/Arachidonic Acid
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)
Plasma 8-isoprostaglandin-F2a/Arachidonic acid concentration, calculated as 8-isoprostaglandin-F2a/Arachidonic acid AUC from 0-180 minutes
8-isoprostaglandin-F2a/Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Arachidonic Acid
Time Frame: Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)
Arachidonic acid concentration, calculated as Arachidonic acid AUC from 0-180 minutes
Arachidonic acid area under the curve for 3 hours (0, 30, 60, 90, 120, 150, 180 minutes) (change from baseline)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ohio State University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Richard S Bruno, PhD, RD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 24, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 14, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2015H0088

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