Microvascular DysfunctionPhase 1/2NCT03376555
Cheese Consumption and Human Microvascular Function
A Phase 1/2 study testing Low sodium no cheese, Low sodium cheese and High sodium no cheese in people with Microvascular Dysfunction, run by Lacy Alexander at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Microvascular Dysfunction
- What is being tested?
- Low sodium no cheese, Low sodium cheese and High sodium no cheese
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2017to 1 Mar 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Seated systolic pressure 120-140 mmHg
- Seated diastolic pressure 70-90 mmHg.
- Normoglycemic (HbA1C <5.7%)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Pennsylvania State University
University Park, Pennsylvania, 16802
About this study
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.
Read the 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.
- Conditions
- Microvascular Dysfunction
- Being tested
- Low sodium no cheese, Low sodium cheese, High sodium no cheese, High sodium cheese
- Keywords
- Sodium, Hypertension, Blood Pressure, Cardiovascular Disease, Nitric Oxide, Skin, Dairy, Cheese, Oxidative Stress, Diet, Flow Mediated Vasodilation, Nitroglycerin, Superoxide, Microcirculation
- Medical subject headings
- Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low sodium no cheeseDietary supplement
Diet contains 1,500 mg sodium per day Diet does not contain dairy cheese 8 days
Low sodium cheeseDietary supplement
Diet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days
High sodium no cheeseDietary supplement
Diet contains 5,500 mg sodium per day Diet does not contain dairy cheese 8 days
High sodium cheeseDietary supplement
Diet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days
| Study group | Role | What they receive |
|---|---|---|
| Impact of Dairy and Sodium on Microvascular Health | Experimental | Cross over design with a baseline and 4 dietary interventions Receives: Dietary Supplement: Low sodium no cheese; Dietary Supplement: Low sodium cheese; Dietary Supplement: High sodium no cheese; Dietary Supplement: High sodium cheese |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular Reactivity to Acetylcholine
Skin blood flow is measured with laser Doppler flowmetry (flux units) and normalized to cutaneous vascular conductance by dividing by mean arterial pressure. Log molar increasing concentrations of acetylcholine are perfused and dose response curves are generated. Dose response curves were analyzed to determine the logEC50 (log Molar)
Measured: 1 hour
Secondary outcomes (3)
Systolic Blood Pressure
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.
Measured: 8 days
Diastolic Blood Pressure
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.
Measured: 8 days
Flow Mediated Dilation
Flow mediated dilation is measured through Doppler ultrasound probe placed at brachial artery.
Measured: 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2017
- Study start1 Jul 2017
- Primary completion1 Mar 2021
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Microvascular DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- 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
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lacy Alexander
- Sponsor type
- University, hospital or other
- Collaborators
- National Dairy Council
- Responsible party
- Sponsor-investigator, Lacy Alexander, Penn State University
- Investigators
- Lacy M Alexander, PhD, Principal investigator, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03376555
- Sponsor's protocol ID
- STUDY4340
- Other IDs
- 129552
- Status last verified
- May 2025
- First submitted
- 13 Dec 2017
- Last updated
- 4 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alba BK, Stanhewicz AE, Dey P, Bruno RS, Kenney WL, Alexander LM. Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide. J Nutr. 2020 Jan 1;150(1):55-63. doi: 10.1093/jn/nxz205.
PubMed 31504721
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cheese Consumption and Human Microvascular Function
- ClinicalTrials.gov ID
- NCT03376555
- Acronym / sponsor ID
- STUDY4340
- Conditions
- Microvascular Dysfunction
- Keywords
- Sodium, Hypertension, Blood Pressure, Cardiovascular Disease, Nitric Oxide, Skin, Dairy, Cheese
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Lacy AlexanderUniversity, hospital or other
- Collaborators
- National Dairy Council
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 18 Dec 2017 (actual)
- Results
- Posted 4 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Impact of Dairy and Sodium on Microvascular Health | Experimental | Dietary Supplement: Low sodium no cheese, Dietary Supplement: Low sodium cheese, Dietary Supplement: High sodium no cheese, Dietary Supplement: High sodium cheeseCross over design with a baseline and 4 dietary interventions |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Seated systolic pressure 120-140 mmHg
- Seated diastolic pressure 70-90 mmHg.
- Normoglycemic (HbA1C <5.7%)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low sodium no cheeseDiet contains 1,500 mg sodium per day Diet does not contain dairy cheese 8 days | Dietary supplement | Impact of Dairy and Sodium on Microvascular Health |
| Low sodium cheeseDiet contains 1,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days | Dietary supplement | Impact of Dairy and Sodium on Microvascular Health |
| High sodium no cheeseDiet contains 5,500 mg sodium per day Diet does not contain dairy cheese 8 days | Dietary supplement | Impact of Dairy and Sodium on Microvascular Health |
| High sodium cheeseDiet contains 5,500 mg sodium per day Diet contains 6 oz dairy cheese per day 8 days | Dietary supplement | Impact of Dairy and Sodium on Microvascular Health |
Primary outcome
Microvascular Reactivity to Acetylcholine
Time frame: 1 hour
Skin blood flow is measured with laser Doppler flowmetry (flux units) and normalized to cutaneous vascular conductance by dividing by mean arterial pressure. Log molar increasing concentrations of acetylcholine are perfused and dose response curves are generated. Dose response curves were analyzed to determine the logEC50 (log Molar)
3 secondary outcomes
Systolic Blood Pressure
Time frame: 8 days
Diastolic Blood Pressure
Time frame: 8 days
Flow Mediated Dilation
Time frame: 8 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31504721Alba BK, Stanhewicz AE, Dey P, Bruno RS, Kenney WL, Alexander LM. Controlled Feeding of an 8-d, High-Dairy Cheese Diet Prevents Sodium-Induced Endothelial Dysfunction in the Cutaneous Microcirculation of Healthy, Older Adults through Reductions in Superoxide. J Nutr. 2020 Jan 1;150(1):55-63. doi: 10.1093/jn/nxz205.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lacy M Alexander, PhD principal investigator
Penn State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Low sodium no cheese, Low sodium cheese and High sodium no cheese in people with Microvascular Dysfunction, run by Lacy Alexander at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Microvascular Reactivity to Acetylcholine (time frame: 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03376555, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2025.