AzTrials
AzTrials

MetabolismNCT04255368

Choline Source, Gut Microbiota and Trimethylamine-N-oxide Response

A study testing Water-soluble choline and Fat-soluble choline in people with Metabolism, run by Utah State University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this research is to determine the production of trimethylamine-N-oxide (TMAO) from different forms of choline and whether this response is modified by the gut microbiota composition. Read more about this study

Who is it for?
Ages 21 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Metabolism
What is being tested?
Water-soluble choline and Fat-soluble choline
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
9 Nov 2017to 25 Jul 2020
Phase
Interventional
Are there results?
None posted in the registry

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 21 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy men and women of any race or ethnicity
  • Age 21-50 y
  • BMI 20-24.9 kg/m2 or BMI 30-39.9 kg/m2

Who cannot join

  • Age > 50 y
  • BMI outside of the normal-weight or obese range (BMI < 20 kg/m2; BMI 25-29.9 kg/m2; or BMI > or = 40 kg/m2)
  • Pregnant or planning to become pregnant during the course of the study; currently breastfeeding (females)
  • Vegetarians
  • Smokers or recreational drug users
  • Individuals with gastrointestinal diseases or complaints, chronic illnesses or other metabolic diseases (including trimethylaminuria)
  • Individuals who have taken antibiotics within the past 2 months
  • Individuals who are not willing to discontinue pre- and probiotics and dietary supplements for the time leading up to 2 months before the study and during the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Center for Human Nutrition Studies Clinic, Utah State University

    Logan, Utah, 84322

Other trials in United States

About this study

Official title: Effect of Choline Source and Gut Microbiota Composition on Trimethylamine-N-oxide Response in Humans

The purpose of this research is to determine the production of trimethylamine-N-oxide (TMAO) from different forms of choline and whether this response is modified by the gut microbiota composition.

Read the detailed description

The overall goal of this research is to identify dietary and physiological factors contributing to elevated levels of trimethylamine-N-oxide (TMAO), a choline-derived gut-microbiome-dependent metabolite that has been identified to increase cardiovascular disease risk. Our recent findings indicate that the gut microbiome may account for variations in TMAO levels, whereby those with a greater enrichment of Firmicutes to Bacteroidetes had elevated TMAO response to dietary precursor intake. However, the interaction between choline intake and gut microbiota composition as a determinant of interindividual variations in TMAO response has not been investigated. This study sought to i) compare plasma and urinary TMAO response after acute challenge containing different forms of choline; and ii) to determine the association between differences in TMAO response with differences in gut microbiota composition. To accomplish these objectives, a randomized, controlled cross-over study was conducted in healthy participants (n=41). The study incorporated three arms comprised of study meals containing (i) 600 mg choline as choline bitartrate; (ii) 600 mg choline as phosphatidylcholine; or (iii) no choline. Each meal was served with a bagel with margarine-butter spread and one cup of water, administered in a single day and separated by a 1-week washout period. Baseline blood sample was obtained by a phlebotomist using a standard venipuncture procedure, and participants collected their baseline urine sample. They also turned in a one-time self-collected baseline stool sample. Following the consumption of the study meal, serial blood samples were collected at 30 min and 1, 2, 4 and 6 h, and urine samples collected throughout the 6 h study period. At 4.5 h, participants were provided a fixed fruit snack (i.e., 2 single serving prepackaged applesauce) and water.

Conditions
Metabolism
Being tested
Water-soluble choline, Fat-soluble choline, No choline control
Keywords
Dietary precursor, Metabolism, Gut microbiota

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Water-soluble cholineOther

    600 mg choline as choline bitartrate

  • Fat-soluble cholineOther

    600 mg choline as phosphatidylcholine

  • No choline controlOther

    No choline

Study groups in NCT04255368
Study groupRoleWhat they receive
Water-soluble cholineExperimentalA breakfast meal consisting of 1 cup of tomato soup containing 600 mg choline as choline bitartrate; served with a bagel with margarine-butter spread and one cup of water.
Receives: Other: Water-soluble choline
Fat-soluble cholineExperimentalA breakfast meal consisting of 1 cup of tomato soup containing 600 mg choline as phosphatidylcholine; served with a bagel with margarine-butter spread and one cup of water.
Receives: Other: Fat-soluble choline
No cholineActive comparatorA breakfast meal consisting of 1 cup of tomato soup containing no choline; served with a bagel with margarine-butter spread and one cup of water.
Receives: Other: No choline control

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. TMAO metabolite concentration change

    Plasma TMAO metabolite response

    Measured: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours

  2. TMAO metabolite concentration change

    Urinary TMAO metabolite response

    Measured: Urine: study baseline, pooled 6 hours study period

  3. Gut microbiome profile

    16S rRNA

    Measured: Stool: one-time baseline

Secondary outcomes (5)

  1. One-carbon metabolite concentration change

    Plasma choline metabolite response

    Measured: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours

  2. Phosphatidylcholine concentration change

    Plasma phosphatidylcholine response

    Measured: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours

  3. One-carbon metabolite concentration change

    Urinary choline metabolite response

    Measured: Urine: study baseline, pooled 6 hours study period

  4. Inflammation and cardiovascular disease risk marker concentration change

    Plasma TNF-α and IL-6

    Measured: Blood: study baseline to 6 hours

  5. Flavin monooxygenase 3 (FMO3) 472 G>A genotype variant

    Genetic polymorphism

    Measured: Blood: study baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2020
  2. Study start9 Nov 2017
  3. Primary completion16 Jun 2018
  4. Study completion25 Jul 2020

Resources

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
Basic science
Allocation
Randomised
Intervention model
Crossover
Model description
Randomized, controlled crossover design where participants consume 3 meals containing (i) free choline; (ii) phosphatidylcholine; or (iii) no choline in a random order separated by a 1-week washout period
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04255368
Sponsor's protocol ID
8547
Status last verified
Nov 2020
First submitted
22 Jan 2020
Last updated
4 Nov 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.

    PubMed 23614584

  • Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922.

    PubMed 21475195

  • Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, Sutter JL, Caudill MA. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201600324. Epub 2016 Aug 3.

    PubMed 27377678

Questions about this trial

What is this clinical trial studying?

A study testing Water-soluble choline and Fat-soluble choline in people with Metabolism, run by Utah 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 3 inclusion and 8 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 Nov 2020. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

TMAO metabolite concentration change (time frame: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours). The study lists 3 primary outcomes in all. 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 NCT04255368, which also lists 3 linked publications.

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 Nov 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in