Cardiovascular Risk FactorNCT04764162
Choline and Cardiometabolic Health
A study testing Choline in people with Cardiovascular Risk Factor, run by Virginia Polytechnic Institute and State University at 1 site in United States.
Trial summary
Trimethylamine-N-oxide (TMAO), a metabolite produced by gut microbial metabolism of dietary choline, has recently been causally linked to atherosclerosis in animal models and has been shown to be predictive of cardiovascular disease (CVD) risk in some but not all cohort studies. Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Risk Factor
- What is being tested?
- Choline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Aug 2021to 21 Nov 2023
- Phase
- Interventional
- 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 18 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18-79 years
- Weight stable for previous 6 months (+2.0kg)
- Sedentary to recreationally active (<30 min aerobic exercise <2x/wk)
- No plans to gain/lose weight or change physical activity level
- Verbal and written informed consent
- Willing to be randomized to treatment order
- Fully vaccinated against COVID-19
Who cannot join
- BMI > 35 kg/m2
- Smoking
- Pregnant or plans of becoming pregnant
- Vegetarian or Vegan
- Changed dietary patterns within the last month
- Diabetes (or use of diabetes medications) or unstable heart disease
Show all 11Show fewer
- Untreated high blood pressure or high cholesterol
- Health problems that mide it unsafe to participate
- Taking medications, vitamins or supplements that could affect study outcomes (including but not limited to aspirin, antibiotics, prebiotics, and probiotics)
- Known allergy, hypersensitivity, intolerance to choline supplement or its ingredients
- Trimethylaminuria or "fish odor" syndrome
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Polytechnic and State University
Blacksburg, Virginia, 24060
About this study
Official title: Short Term Choline Supplementation and Cardiometabolic Health in Adults
Trimethylamine-N-oxide (TMAO), a metabolite produced by gut microbial metabolism of dietary choline, has recently been causally linked to atherosclerosis in animal models and has been shown to be predictive of cardiovascular disease (CVD) risk in some but not all cohort studies. The relevance of observations in animals to humans is unclear and little information is available on the mechanisms linking TMAO to increased CVD risk. Vascular dysfunction plays a critical role in the initiation and progression of atherothrombotic disease. Whether TMAO impairs vascular function in humans is not known. The purpose of this study is to determine if short term supplementation of dietary choline, which increases TMAO, affects CVD risk factors, such as glucose homeostasis and vascular function.
- Conditions
- Cardiovascular Risk Factor
- Being tested
- Choline, Placebo
- Keywords
- insulin sensitivity, vascular function, blood pressure, continuous glucose monitoring, trimethylamine N-oxide (TMAO)
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CholineDietary supplement
1000 mg (2 x 500 mg) choline bitartrate capsules (over-the-counter supplement)
PlaceboDietary supplement
Choline-matched 1000 mg (2 x 500 mg) placebo (maltodextrin) capsules
| Study group | Role | What they receive |
|---|---|---|
| Choline, then Placebo | Experimental | Participants will consume 1000 mg (2 x 500 mg) of choline supplement per day for 4 weeks, including post-testing sessions. A 2-week washout period will follow the first intervention. Then the participants will consume 1000 mg (2 x 500 mg) of placebo per day for 4 weeks, including post-testing sessions. Receives: Dietary Supplement: Choline; Dietary Supplement: Placebo |
| Placebo, then Choline | Experimental | Participants will consume 1000 mg (2 x 500 mg) of placebo per day for 4 weeks, including post-testing sessions. A 2-week washout period will follow the first intervention. Then the participants will consume 1000 mg (2 x 500 mg) of choline supplement per day for 4 weeks, including post-testing sessions. Receives: Dietary Supplement: Choline; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Insulin Sensitivity at 4 Weeks
Participants will complete a 2-hour glucose tolerance test at baseline, immediately following the first intervention, after a 2-week washout, and immediately following the second intervention. A catheter will be placed in one of the participant's arms. After a baseline blood draw to measure fasting levels of glucose, insulin, cholesterol and other factors, participants will drink a glucose beverage (75 g). Blood will be collected in small amounts (less than one half teaspoon) at eight timepoints over a 2-hour period. Insulin sensitivity will be calculated using Matsuda's index (a ratio with no units). This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).
Measured: Calculated difference between the baseline and 4-week testing session for each intervention
Secondary outcomes (1)
Change in 24-hour Area Under the Curve for Glucose Levels After Supplementation
Glucose will be monitored by a Continuous Glucose Monitor (CGM) sensor (Enlite Sensor; Medtronic, Inc. or FreeStyle Libre Pro; Abbott) and this will be placed on the participant's abdomen or back of the upper arm in order to measure glucose continuously. The measured glucose levels will be assessed by an iPro2 Professional CGM; Medtronic, Inc. or FreeStyle Libre Pro reader; Abbott; and the CGM will be worn for 4 consecutive days. This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).
Measured: Difference in 24-hour glucose levels during free living at baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start20 Aug 2021
- Primary completion2 Dec 2022
- Study completion21 Nov 2023
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.
- Other trials for Cardiovascular Risk FactorStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, placebo-controlled, crossover design
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Polytechnic Institute and State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Kevin Davy, Virginia Polytechnic Institute and State University
- Investigators
- Kevin Davy, PhD, Principal investigator, Virginia Polytechnic Institute & State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764162
- Sponsor's protocol ID
- 25-521
- Other IDs
- R21AG067380
- Status last verified
- May 2025
- First submitted
- 17 Feb 2021
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Term Choline Supplementation and Cardiometabolic Health in Adults
- ClinicalTrials.gov ID
- NCT04764162
- Acronym / sponsor ID
- 25-521
- Conditions
- Cardiovascular Risk Factor
- Keywords
- insulin sensitivity, vascular function, blood pressure, continuous glucose monitoring, trimethylamine N-oxide (TMAO)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Virginia Polytechnic Institute and State UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 20 Aug 2021 (actual)
- Primary completion
- 2 Dec 2022 (actual)
- Study completion
- 21 Nov 2023 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Posted 29 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Trimethylamine-N-oxide (TMAO), a metabolite produced by gut microbial metabolism of dietary choline, has recently been causally linked to atherosclerosis in animal models and has been shown to be predictive of cardiovascular disease (CVD) risk in some but not all cohort studies. The relevance of observations in animals to humans is unclear and little information is available on the mechanisms linking TMAO to increased CVD risk. Vascular dysfunction plays a critical role in the initiation and progression of atherothrombotic disease. Whether TMAO impairs vascular function in humans is not known. The purpose of this study is to determine if short term supplementation of dietary choline, which increases TMAO, affects CVD risk factors, such as glucose homeostasis and vascular function.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, placebo-controlled, crossover design
| Arm | Type | Receives |
|---|---|---|
| Choline, then Placebo | Experimental | Dietary Supplement: Choline, Dietary Supplement: PlaceboParticipants will consume 1000 mg (2 x 500 mg) of choline supplement per day for 4 weeks, including post-testing sessions. A 2-week washout period will follow the first intervention. Then the participants will consume 1000 mg (2 x 500 mg) of placebo per day for 4 weeks, including post-testing sessions. |
| Placebo, then Choline | Experimental | Dietary Supplement: Choline, Dietary Supplement: PlaceboParticipants will consume 1000 mg (2 x 500 mg) of placebo per day for 4 weeks, including post-testing sessions. A 2-week washout period will follow the first intervention. Then the participants will consume 1000 mg (2 x 500 mg) of choline supplement per day for 4 weeks, including post-testing sessions. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18-79 years
- Weight stable for previous 6 months (+2.0kg)
- Sedentary to recreationally active (<30 min aerobic exercise <2x/wk)
- No plans to gain/lose weight or change physical activity level
- Verbal and written informed consent
Key exclusion criteria (11 listed)
- BMI > 35 kg/m2
- Smoking
- Pregnant or plans of becoming pregnant
- Vegetarian or Vegan
- Changed dietary patterns within the last month
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 |
|---|---|---|
| Choline1000 mg (2 x 500 mg) choline bitartrate capsules (over-the-counter supplement) | Dietary supplement | Choline, then Placebo, Placebo, then Choline |
| PlaceboCholine-matched 1000 mg (2 x 500 mg) placebo (maltodextrin) capsules | Dietary supplement | Choline, then Placebo, Placebo, then Choline |
Primary outcome
Change From Baseline in Insulin Sensitivity at 4 Weeks
Time frame: Calculated difference between the baseline and 4-week testing session for each intervention
Participants will complete a 2-hour glucose tolerance test at baseline, immediately following the first intervention, after a 2-week washout, and immediately following the second intervention. A catheter will be placed in one of the participant's arms. After a baseline blood draw to measure fasting levels of glucose, insulin, cholesterol and other factors, participants will drink a glucose beverage (75 g). Blood will be collected in small amounts (less than one half teaspoon) at eight timepoints over a 2-hour period. Insulin sensitivity will be calculated using Matsuda's index (a ratio with no units). This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).
1 secondary outcome
Change in 24-hour Area Under the Curve for Glucose Levels After Supplementation
Time frame: Difference in 24-hour glucose levels during free living at baseline and 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kevin Davy, PhD principal investigator
Virginia Polytechnic Institute & State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Choline in people with Cardiovascular Risk Factor, run by Virginia Polytechnic Institute and State University 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 7 inclusion and 11 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 31 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Nov 2024). 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?
Change From Baseline in Insulin Sensitivity at 4 Weeks (time frame: Calculated difference between the baseline and 4-week testing session for each intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 May 2025.