Effect of Plasma Ceramides on Peripheral Vascular Function

June 25, 2025 updated by: Julie K. Freed, Medical College of Wisconsin
The goal of this clinical trial is to determine the effect of elevated plasma ceramides on peripheral vascular function. Subjects will consume a high fat meal consisting of long chain fatty acids (to increase plasma ceramides) or medium chain fatty acids (control). Subjects' vascular function will be assessed with laser Doppler flowmetry to measure their artery function and with the CytoCam device to assess their peripheral microvascular endothelial function.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Purpose: The overarching goal of this project is to correlate the effects of plasma ceramide with human in vivo vascular function.

Formulation of Research Questions: Following decades of decline in mortality, death due to heart disease is increasing, and remains the #1 cause of death in the United States. Although acute ischemic events are typically due to obstructive plaque within the coronary conduit arteries, strong evidence suggests that dysfunction within the coronary microvasculature is a more powerful predictor of major adverse cardiac events (MACE) than severity of atherosclerosis1. The coronary microvasculature likely also contributes to other forms of cardiovascular disease including heart failure with preserved ejection fraction (HFpEF)2. While assessment of the coronary microvasculature is highly invasive and expensive, interrogation of the peripheral microvasculature offers a more feasible approach. Recent studies have concluded that peripheral microvascular dysfunction mirrors the functional status of the coronary microvasculature3. Further, impaired peripheral microvascular function is associated with increased risk of MACE in patients with stable coronary artery disease (CAD), suggesting that the microvasculature plays a critical role in the pathogenesis of heart disease4.

Elevated plasma ceramides are also associated with risk of MACE in otherwise healthy individuals5 as well as in heart failure both with and without reduced ejection fraction (HFrEF and HFpEF, respectively)6. Recently it was shown that ceramide levels are increased in patients with early CAD that also exhibit impaired coronary microvascular endothelial dysfunction7. Using an in vitro model, the investigators have previously shown that exposure to exogenous ceramide causes microvascular endothelial dysfunction in arterioles from healthy individuals8. However the effect of ceramide on human in vivo peripheral microvascular function represents a critical knowledge gap that needs to be addressed. Increased plasma ceramide may evoke peripheral in vivo microvascular dysfunction that mirrors that of the coronary microvasculature thus providing a less invasive means to assess future cardiovascular risk.

Hypothesis: Following a single high-fat meal, increases in plasma ceramides will correlate with a reduction in peripheral large and small vascular function in the intact human adult.

At Adult TRU:

  1. Patient arrives at the Adult Translational Unit (ATRU) and checks in with the nurse at the front desk.
  2. TRU nurse informs study team that the subject has arrived.
  3. Dr. Freed or study team member consents the subject.

  4. Once the subject completes the consent form, the nurse brings them to the patient room.

    1. If the subject is female, they are required to take a pregnancy test.
    2. The nurse completes the pregnancy test and gives the results to the study team member.
    3. The nurse takes baseline vital signs (height, weight, blood pressure, heart rate).

  5. Baseline testing begins: (time 0)

    1. Baseline blood draw (10mL) to measure plasma ceramide levels.
    2. Baseline flow-mediated dilation (FMD) and reactive hyperemia measurements
    3. Baseline cytocam assessment
  6. High-fat meal: Subjects will be given one high-fat meal by the ATRU dietitian to be ingested within 20 minutes.

  7. 2-hour timepoint testing: (time 2)

    1. Blood draw (10mL) at 2hrs post initiation of high-fat meal to measure ceramide levels
    2. FMD and reactive hyperemia measurements

  8. 4-hour timepoint testing: (time 4)

    1. Blood draw (10mL) at 4hrs post initiation of high-fat meal to measure ceramide levels
    2. FMD and reactive hyperemia measurements
    3. 4-hour cytocam assessment

  9. After the study is completed, the patient remains in the exam room for 30 min under nurse observation

    1. During this time, vital signs are assessed by the nurse
    2. The patient may order food off the Froedtert menu

Flow-Mediated Dilation/Reactive Hyperemia Protocol Flow mediated dilation (FMD) and blood flow velocity will be assessed using a portable ultrasound machine with a 13 mHz probe. All images will be continuously captured onto using the Vascular Imager (Medical Imaging, Iowa City, IA) software. Artery diameter will automatically be measured using the boarder sensing function in the Brachial Analyzer (Medical Imaging) software.

After the subjects have rested in the supine position for 15 minutes their arm will be abducted ~80° with the pneumatic cuff placed on their forearm. Baseline brachial artery diameter and blood flow velocity through the artery will be measured 3 cm proximal to the antecubital fossa. The ultrasound probe will be positioned at 90° to the vessel to visualize anterior and posterior lumen-intimal interfaces. After baseline images have been captured, the pneumatic cuff will be inflated to 225 mmHg for 5 minutes to occlude blood flow to the lower leg or forearm. Immediately after cuff release, the increased blood flow velocity due to the reactive hyperemia response will be measured. To assess vasodilation, images will be captured at a rate of 10 images/second for 3 minutes after cuff release.

Cytocam Assessment for Microvascular Function Approximately 10 images will be taken to establish a baseline. The study team will administer 1% acetylcholine (via Q-tip, liquid dropper or gauze) under the tongue for 1 minute. The CytoCam is reinserted to take approximately 10 more images. The patient will be allowed 30 minutes to rest while the nurse retakes vital signs. After 30 minutes, a new set of approximately 10 baseline images are taken. The study team will administer a nitroglycerin tablet (0.3mg) under the tongue. Once the tablet dissolves the CytoCam will be reinserted to image the vessels (approximately 10 images) after 2-3 minutes following tablet administration.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • 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
    • Wisconsin
      • Wauwatosa, Wisconsin, United States, 53226
        • Froedtert Hospital

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

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Health adults aged 18-40 years
  2. English-speaking only
  3. Not pregnant

Exclusion Criteria:

  1. Healthy individuals under 18 years or over 40 years of age
  2. Non-English speaking
  3. Pregnant individuals
  4. Heart rate <60 or >100
  5. Systolic blood pressure <100 or >160
  6. Subjects with visible open sores or wounds in mouth
  7. Lactose intolerant or allergy to dairy products
  8. Diabetes Mellitus
  9. Coronary Artery Disease
  10. High blood pressure
  11. High cholesterol
  12. Heart failure
  13. Current tobacco use
  14. Chemotherapy within the last 6 months

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Medium Chain Fatty Acid High Fat Meal
This arm will assess the effect of increased plasma ceramide on peripheral microvascular function after consuming a medium chain fatty acid high fat meal.
Other: High Saturated Fat
High saturated fat meal
Experimental: Long Chain Fatty Acid High Fat Meal
This arm will assess the effect of increased plasma ceramide on peripheral microvascular function after consuming a long chain fatty acid high fat meal.
Other: High Saturated Fat
High saturated fat meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Cardiovascular Conductance
Time Frame: 6 hours
Use laser Doppler flowmetry to measure blood flow
6 hours
Endothelial-Dependent Total Vessel Density
Time Frame: 6 hours
Use a microscope (CytoCam) to look at blood vessels
6 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reactive Hyperemia
Time Frame: Year 2
Measure the volume of flow following cuff release
Year 2
Endothelial-Dependent Total Vessel Density
Time Frame: Year 2
Use incident dark field technology to assess endothelial dependent increases in total vessel density
Year 2

Collaborators and Investigators

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

Sponsor

Medical College of Wisconsin

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 (Actual)

May 1, 2023

Primary Completion (Actual)

May 7, 2025

Study Completion (Actual)

May 7, 2025

Study Registration Dates

First Submitted

October 4, 2021

First Submitted That Met QC Criteria

November 3, 2021

First Posted (Actual)

November 4, 2021

Study Record Updates

Last Update Posted (Actual)

June 29, 2025

Last Update Submitted That Met QC Criteria

June 25, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 00041566

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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