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Cheese Consumption and Human Microvascular Function

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ClinicalTrials.gov Identifier: NCT03376555
Recruitment Status : Recruiting
First Posted : December 18, 2017
Last Update Posted : December 20, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Increased dairy intake is associated with improved measures of blood vessel health. Dairy cheese, however, is often high in sodium. Dietary sodium can impair blood vessel function. The researchers examine if and how natural cheese may protect against impairments in blood vessel function caused by sodium. For this study, participants complete four 8-day controlled feeding periods in which they eat cheese (6 oz/day) or no cheese during a low-sodium or high-sodium base-diet. The participants complete baseline experiments while on their normal personal diet and then repeat experiments at the end of each controlled feeding period. In some of our experiments, the researchers use a technique called "microdialysis" (MD). With MD, the researchers perfuse some research drugs into the skin on the forearm through tiny tubing that mimics capillaries. These MD drugs mimic or block substances the body naturally makes to control the small blood vessels in the skin. The drugs remain in nickel-sized areas around the tubing and do not go into the rest of the body. The researchers also use a standard technique called "flow mediated dilation" (FMD) that uses blood pressure cuffs and ultrasound to look at the health of larger blood vessels in the body. FMD includes placing a small tablet of nitroglycerin under the tongue during part of the test.

Condition or disease Intervention/treatment Phase
Microvascular Dysfunction Drug: Acetylcholine (ACh) Dose Response Drug: Local Heating (LH) Drug: Flow Mediated Dilation with nitroglycerin Phase 1 Phase 2

Detailed Description:

Subject screening will be performed by the Penn State Clinical Translational Research Center (CTRC) medical staff and will include a physical exam by a clinician, anthropometry, and a chemical and lipid profile, liver and renal function. Participants meet with a registered dietitian to determine their caloric energy requirements and identify food preferences. The interview includes surveying the subject's physical activity over the previous 7 days.

Subjects will undergo baseline microdialysis experiments to examine the function of the blood vessels in the skin microcirculation. Subjects will also go through a baseline assessment of conduit vessel endothelial and vascular smooth muscle function with brachial artery flow-mediated vasodilation (FMD), and sublingual nitroglycerin. Following baseline experiments, subjects participate in 4 controlled feeding periods, each 8 days in duration. The controlled feeding periods are assigned in a randomized order. At the end of each 8-day controlled dietary period, subjects will repeat microdialysis experiments, brachial artery FMD, and responsiveness to sublingual nitroglycerin.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: All subjects participate in 4 diets in randomized order. The diets differ in the amount of sodium and dairy cheese content. Each diet is consumed for 8 days. Minimum washout of 1 week between diets. Baseline experiment is conducted prior to first dietary intervention, and the experiment is repeated after each dietary intervention.
Masking: Double (Investigator, Outcomes Assessor)
Masking Description: Investigator and Outcomes Assessor are masked according to treatment.
Primary Purpose: Basic Science
Official Title: Cheese Consumption and Human Microvascular Function
Actual Study Start Date : March 2016
Estimated Primary Completion Date : June 30, 2018
Estimated Study Completion Date : June 30, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Baseline
Subjects on normal personal diet Acetylcholine (ACh) Dose Response, Local heating (LH), and Flow Mediated Dilation with nitroglycerin experiments
Drug: Acetylcholine (ACh) Dose Response
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + N-G-nitro-L-arginine methyl ester (LNAME) Probe 3. Lactated Ringer's + Ascorbate Probe 4. Lactated Ringer's + Tempol Probe 5. Lactated Ringer's + Apocynin
Other Name: ACh Dose Response
Drug: Local Heating (LH)
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + Ascorbate Probe 3. Lactated Ringer's + Tempol Probe 4. Lactated Ringer's + Apocynin
Other Name: LH
Drug: Flow Mediated Dilation with nitroglycerin

BP cuff on a forearm, gel on the upper arm just above the elbow, and a Doppler ultrasound probe on the gel. The ultrasound measures vessel size and blood velocity. After a 3-minute "resting" measurement, the cuff inflates for 5 minutes to occlude forearm blood flow (BF). After the cuff deflates, we perform a second reading.

Sublingual nitroglycerin: The subject is supine. We measure blood pressure. Also, we perform ultrasonography at the brachial artery at the elbow during the procedure. Nurse places a 0.4 mg nitroglycerin tablet under the subject's tongue. The subject remains supine for 20 minutes following the nitroglycerin administration.

Other Name: FMD
Experimental: Low Sodium, No Cheese

Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese

After 8 days on diet:

Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments

Drug: Acetylcholine (ACh) Dose Response
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + N-G-nitro-L-arginine methyl ester (LNAME) Probe 3. Lactated Ringer's + Ascorbate Probe 4. Lactated Ringer's + Tempol Probe 5. Lactated Ringer's + Apocynin
Other Name: ACh Dose Response
Drug: Local Heating (LH)
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + Ascorbate Probe 3. Lactated Ringer's + Tempol Probe 4. Lactated Ringer's + Apocynin
Other Name: LH
Drug: Flow Mediated Dilation with nitroglycerin

BP cuff on a forearm, gel on the upper arm just above the elbow, and a Doppler ultrasound probe on the gel. The ultrasound measures vessel size and blood velocity. After a 3-minute "resting" measurement, the cuff inflates for 5 minutes to occlude forearm blood flow (BF). After the cuff deflates, we perform a second reading.

Sublingual nitroglycerin: The subject is supine. We measure blood pressure. Also, we perform ultrasonography at the brachial artery at the elbow during the procedure. Nurse places a 0.4 mg nitroglycerin tablet under the subject's tongue. The subject remains supine for 20 minutes following the nitroglycerin administration.

Other Name: FMD
Experimental: Low Sodium, Cheese

Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day

After 8 days on diet:

Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments

Drug: Acetylcholine (ACh) Dose Response
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + N-G-nitro-L-arginine methyl ester (LNAME) Probe 3. Lactated Ringer's + Ascorbate Probe 4. Lactated Ringer's + Tempol Probe 5. Lactated Ringer's + Apocynin
Other Name: ACh Dose Response
Drug: Local Heating (LH)
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + Ascorbate Probe 3. Lactated Ringer's + Tempol Probe 4. Lactated Ringer's + Apocynin
Other Name: LH
Drug: Flow Mediated Dilation with nitroglycerin

BP cuff on a forearm, gel on the upper arm just above the elbow, and a Doppler ultrasound probe on the gel. The ultrasound measures vessel size and blood velocity. After a 3-minute "resting" measurement, the cuff inflates for 5 minutes to occlude forearm blood flow (BF). After the cuff deflates, we perform a second reading.

Sublingual nitroglycerin: The subject is supine. We measure blood pressure. Also, we perform ultrasonography at the brachial artery at the elbow during the procedure. Nurse places a 0.4 mg nitroglycerin tablet under the subject's tongue. The subject remains supine for 20 minutes following the nitroglycerin administration.

Other Name: FMD
Experimental: High Sodium, No Cheese

Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese

After 8 days on diet:

Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments

Drug: Acetylcholine (ACh) Dose Response
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + N-G-nitro-L-arginine methyl ester (LNAME) Probe 3. Lactated Ringer's + Ascorbate Probe 4. Lactated Ringer's + Tempol Probe 5. Lactated Ringer's + Apocynin
Other Name: ACh Dose Response
Drug: Local Heating (LH)
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + Ascorbate Probe 3. Lactated Ringer's + Tempol Probe 4. Lactated Ringer's + Apocynin
Other Name: LH
Drug: Flow Mediated Dilation with nitroglycerin

BP cuff on a forearm, gel on the upper arm just above the elbow, and a Doppler ultrasound probe on the gel. The ultrasound measures vessel size and blood velocity. After a 3-minute "resting" measurement, the cuff inflates for 5 minutes to occlude forearm blood flow (BF). After the cuff deflates, we perform a second reading.

Sublingual nitroglycerin: The subject is supine. We measure blood pressure. Also, we perform ultrasonography at the brachial artery at the elbow during the procedure. Nurse places a 0.4 mg nitroglycerin tablet under the subject's tongue. The subject remains supine for 20 minutes following the nitroglycerin administration.

Other Name: FMD
Experimental: High Sodium, Cheese

Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day

After 8 days on diet:

Acetylcholine Dose Response, Local heating, and Flow Mediated Dilation with nitroglycerin experiments

Drug: Acetylcholine (ACh) Dose Response
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + N-G-nitro-L-arginine methyl ester (LNAME) Probe 3. Lactated Ringer's + Ascorbate Probe 4. Lactated Ringer's + Tempol Probe 5. Lactated Ringer's + Apocynin
Other Name: ACh Dose Response
Drug: Local Heating (LH)
Probe 1. Lactated Ringer's only (control) Probe 2. Lactated Ringer's + Ascorbate Probe 3. Lactated Ringer's + Tempol Probe 4. Lactated Ringer's + Apocynin
Other Name: LH
Drug: Flow Mediated Dilation with nitroglycerin

BP cuff on a forearm, gel on the upper arm just above the elbow, and a Doppler ultrasound probe on the gel. The ultrasound measures vessel size and blood velocity. After a 3-minute "resting" measurement, the cuff inflates for 5 minutes to occlude forearm blood flow (BF). After the cuff deflates, we perform a second reading.

Sublingual nitroglycerin: The subject is supine. We measure blood pressure. Also, we perform ultrasonography at the brachial artery at the elbow during the procedure. Nurse places a 0.4 mg nitroglycerin tablet under the subject's tongue. The subject remains supine for 20 minutes following the nitroglycerin administration.

Other Name: FMD


Outcome Measures

Primary Outcome Measures :
  1. laser Doppler blood flow [ Time Frame: 8 weeks ]
    This measurement is performed using a laser Doppler flow meter. The flow meter produces a non-invasive qualitative and dimensionless index of blood flow in blood vessels.


Secondary Outcome Measures :
  1. Systolic Blood Pressure [ Time Frame: 8 weeks ]
    Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The peak blood pressure during a cardiac cycle when the heart contracts.

  2. Diastolic Blood Pressure [ Time Frame: 8 weeks ]
    Blood pressure is measured via brachial auscultation manually or with a critical care monitor. The lowest blood pressure during a cardiac cycle when the heart is between beats.

  3. Flow Mediated Dilation [ Time Frame: 8 weeks ]
    Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Seated systolic pressure 120-140 mmHg
  • Seated diastolic pressure 70-90 mmHg.
  • Normoglycemic (HbA1C <5.7%)

Exclusion Criteria:

  • Taking pharmacotherapy that alters peripheral vascular control
  • Pregnancy
  • Breastfeeding
  • Females taking contraceptives (pills, patches, shots, etc.) or hormone replacement therapy
  • Taking illicit and/or recreational drugs
  • Use of nicotine containing-products (e.g. smoking, chewing tobacco, etc.)
  • Known allergy to latex or investigative substances
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376555


Contacts
Contact: Susan K Slimak, RN 814-863-8556 sks31@psu.edu
Contact: Billie K Alba, MBA 814-863-8557 bka125@psu.edu

Locations
United States, Pennsylvania
Pennsylvania State University Recruiting
University Park, Pennsylvania, United States, 16802
Sponsors and Collaborators
Lacy M. Alexander
National Dairy Council
Investigators
Principal Investigator: Lacy M Alexander, PhD Penn State University
More Information

Responsible Party: Lacy M. Alexander, Associate Professor of Kinesiology, Penn State University
ClinicalTrials.gov Identifier: NCT03376555     History of Changes
Other Study ID Numbers: STUDY4340
129552 ( Other Identifier: FDA )
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lacy M. Alexander, Penn State University:
Sodium
Hypertension
Blood Pressure
Cardiovascular Disease
Nitric Oxide
Skin
Dairy
Cheese
Oxidative Stress
Diet
Flow Mediated Vasodilation
Nitroglycerin
Superoxide
Microcirculation

Additional relevant MeSH terms:
Nitroglycerin
Acetylcholine
Vasodilator Agents
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs