Choline Nutritional Status: Development of a Biomarker Panel

Study at a glance

From the registry record, last updated by the sponsor on 6 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Choline Nutritional Status: Development of a Biomarker Panel

ClinicalTrials.gov ID

NCT03726671

Acronym / sponsor ID

17-1982

Conditions

Healthy

Study type

Interventional

Recruitment status

Completed

Enrolment

101 participants (actual)

Lead sponsor

University of North Carolina, Chapel HillUniversity, hospital or other

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study start

1 Nov 2018 (actual)

Primary completion

20 Oct 2021 (actual)

Study completion

20 Oct 2021 (actual)

First posted

31 Oct 2018 (actual)

Results

Posted 6 Jan 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Screening

Allocation

Randomised

Intervention model

Crossover

Masking

Triple blind (participant, investigator, outcomes assessor)

Number of arms

6

Model description

Healthy volunteers will consume meals, provided by the investigator, in two week intervals with 3 different levels of choline (Cho). Participants will receive 100% of the recommended daily intake (RDI) of Cho (550 mg Cho/day); 50% of the RDI of Cho (275mg/day); and 25% of the RDI of Cho (137.5 mg/day). The meal order will be randomly assigned and all participants will receive all diets at some point in the study. There will be a minimum of a two week washout between diet intervals where participants return to their regular diets. Both participants and researchers will be blinded to the diet order.

Who may qualify

Ages

17 to 70 years

Sex

All

Healthy volunteers

Accepted

Age groups

Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Ratio of Liver Choline Pool Size by Isotope Dilution

   Time frame: 24 hours following administration of choline-d9 on day 12 of respective dietary intervention

   The liver choline pool determined by the dilution of the deuterated choline metabolites formed in liver and released to plasma as measured by isotopic enrichment ratio (IER). The IER for a given metabolite is defined as the concentration of a deuterated metabolite divided by the sum of deuterated and non-deuterated metabolite.

2. Difference in Choline Deficiency Signature

   Time frame: At the end of 2 weeks of respective Cho diet

   Plasma choline metabolites (micromolar): choline, dimethylglycine, betaine, phosphatidylcholine, sphingomyelin, trimethylamine-oxide, and homocysteine measured by targeted metabolomic profiling. The signature for choline deficiency is defined by choline <0.793 mmol/L or betaine <34.9 mmol/L. The levels of these metabolites at the end of each intervention will be compared. The association between choline metabolites and choline pool size will be investigated.

3. Comparison of Choline Pool Size Between Participants With and Without Choline Metabolites Signature During Cho Depletion

   Time frame: 24 hours following administration of choline-d9 on day 12 of 25% Cho diet

   The 25% Cho arm was selected because only at that intake level is sufficient depletion achieved. Participants with plasma choline <0.793 mmol/L or betaine <34.9 mmol/L were considered as choline depleted (showing signature), participants with plasma choline >=0.793 mmol/L and betaine >=34.9 mmol/L were considered as not choline depleted (not showing signature). Available choline pool size was determined by the dilution of the deuterated choline metabolites formed in liver and released to plasma as measured by isotopic enrichment ratio (IER). The IER for a given metabolite is defined as the concentration of a deuterated metabolite divided by the sum of deuterated and non-deuterated metabolite.

4. Ion Abundance (Intensity) of Metabolites as Indicators of the Intake of 25%, 50%, or 100% Choline in the Diet. The Ratio of the Intensity of Metabolite Signals for Each Dietary Group Can be Calculated and Correlated With the Level of Choline in the Diet

   Time frame: At the end of 2 weeks of respective Cho diet

   Metabolomics was conducted on plasma that was collected from individuals at the end of each 2-week diet period. UHPLC High Resolution Mass Spectrometry was used for differential profiling (PMID: 33415121). Supervised Orthogonal Partial Least Squares Discriminant Analysis was used to determine signals that differentiated the 25% choline dietary group from the 100% choline dietary group. Metabolites that differentiated the 25% and 100% choline dietary groups with variable importance to projection (VIP) >1 and p-value < 0.05 are reported. The signals for these metabolites were matched by retention time, exact mass, and MS/MS to standards run on the same platform. Because this is a differential profiling method (not quantitative), the mean and standard deviation of peak intensities detected on the untargeted platform are reported. Results are reported for the selected metabolites for the 25%, 50%, and 100% choline dietary groups. Ratios can be obtained by division of the intensity data.

5. Comparison of Choline Pool Size Between Participants With Different Genotypes in Phosphatidylethanolamine-N-methyltransferase (PEMT) Single Nucleotide Polymorphism (SNP rs12325817)

   Time frame: 24 hours following administration of choline-d9 on day 12 of respective dietary intervention

   DNA was collected and evaluated for the presence of the PEMT SNP rs12325817. Genotypes was measured by real time polymerase chain reaction (RT-PCR). The magnitude of changes in choline pool size as measured by IER at the end of each dietary intervention was compared among subjects with different genotypes in the PEMT SNP. Linear mixed model with repeated measures was performed for each group (healthy males, pre- and postmenopausal females) separately to study the genotype effect and genotype x diet interaction effect on choline pool size.

6. Change in Liver Fat Content Based on CAP Values

   Time frame: Day 1 and Day 15 of respective Cho diet

   Controlled attenuation parameter (CAP) as measured by Fibroscan is an ultrasound-based technique to measure liver fat. This method will be used with other biomarkers to indicate functional signs of choline status.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2023.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 41687879Trujillo-Gonzalez I, Horita DA, Stegall J, Coble R, Paules EM, Lulla AA, Baah E, Bottiglieri T, Sha W, Kohlmeier M, Friday WB, Zeisel SH. Choline and betaine concentrations in plasma discriminate levels of dietary choline intake in healthy adults: analysis of a double-blind randomized crossover controlled feeding study. Am J Clin Nutr. 2026 Apr;123(4):101236. doi: 10.1016/j.ajcnut.2026.101236. Epub 2026 Feb 11.
• Derived from this study: PubMed 33668062Horita DA, Hwang S, Stegall JM, Friday WB, Kirchner DR, Zeisel SH. Two methods for assessment of choline status in a randomized crossover study with varying dietary choline intake in people: isotope dilution MS of plasma and in vivo single-voxel magnetic resonance spectroscopy of liver. Am J Clin Nutr. 2021 Jun 1;113(6):1670-1678. doi: 10.1093/ajcn/nqaa439.

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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.

1 site in 1 country: see every site and its status.