Developing a Biomarker Panel to Assess Choline Nutritional Status
1 other identifier
interventional
16
1 country
1
Brief Summary
People who eat diets low in choline (LC) should deplete their choline (Cho) stores, and measurements of Cho pool size using isotope dilution should reflect this depletion. Investigators will identify a biomarker panel that correlates well with measured Cho pool size across the range of different degrees of depletion.The investigators propose that, as body stores of Cho diminish, cells and organs will reach the point when metabolism/function in the cell is altered, and that this will result in a progression of changes in biomarkers that reflect Cho status.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable healthy
Started Feb 2018
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 19, 2017
CompletedFirst Posted
Study publicly available on registry
July 31, 2017
CompletedStudy Start
First participant enrolled
February 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 18, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 18, 2018
CompletedDecember 3, 2019
December 1, 2019
8 months
July 19, 2017
December 2, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Change in biomarker panel measures and MRS/MRI scans correlated to different dietary choline levels
The investigator will evaluate direct measures of Choline derived pools and using isotope dilution will provide an estimate of the size of the body pool of choline, while also profiling choline-related metabolites. MRS/MRI will assess Cho compounds in liver and fatty liver (also used to validate Fibroscan) to confirm measures utilizing isotope dilution.
Samples taken on Day 12 and Day 14
Secondary Outcomes (2)
Genotyping for choline metabolism single nucleotide polymorphisms
At baseline visit
Metabolomic profiling to enhance Cho status score
Samples taken on Day 15
Study Arms (6)
25%Cho, 50%Cho, 100%Cho
EXPERIMENTALDiets containing 137.5mg (25% Cho diet), 275mg (50% Cho diet), and 550mg (100% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
25% Cho, 100% Cho, 50% Cho
EXPERIMENTALDiets containing 137.5mg (25% Cho diet) , 550mg (100% Cho diet), and 275mg Cho (50% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
50% Cho, 25% Cho, 100% Cho
EXPERIMENTALDiets containing 275mg (50% Cho diet), 137.5mg (25% Cho diet), and 550mg Cho (100% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
50% Cho, 100% Cho, 25% Cho
EXPERIMENTALDiets containing 275mg (50% Cho diet), 550mg (100% Cho diet), and 137.5mg Cho (25% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
100% Cho, 25% Cho, 50% Cho
EXPERIMENTALDiets containing 550mg (100% Cho diet), 137.5mg (25% Cho diet), and 275mg Cho (50% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
100% Cho, 50% Cho, 25% Cho
EXPERIMENTALDiets containing 550mg (100% Cho diet), 275mg (50% Cho diet), and 137.5mg Cho (25% Cho diet) will be given in that order for two weeks each with 2 weeks of washout between.
Interventions
Subjects will consume meals containing 25% of the recommended intake of Choline (137.5 mg Choline/day) for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride-(trimethyl-d9, 9%, Cambridge Isotope Laboratories, Tewksbury, Massachusetts, (USA), as a bolus.
Subjects will consume meals containing 50% of the recommended intake of Choline (275 mg Choline/day) for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride-(trimethyl-d9, 9%, Cambridge Isotope Laboratories, Tewksbury, Massachusetts, (USA), as a bolus.
Subjects will consume meals containing 100% of the recommended intake of Choline (550 mg Choline/day) for 2 weeks. On day 12 of the diet period, subjects will consume 250 mg of Cho in the form of Cho chloride-(trimethyl-d9, 9%, Cambridge Isotope Laboratories, Tewksbury, Massachusetts, (USA), as a bolus.
Eligibility Criteria
You may qualify if:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 17-70 years
- In good general health as evidenced by medical history, clinical chemistries, physical exam, and BMI≤ 30
- Women who are included in the study and are of pregnancy potential will have a urine pregnancy test at the beginning and end of each dietary intervention arm and must be using birth control during the study.
You may not qualify if:
- using drugs or medication known to be damaging to liver or muscle at typically prescribed doses or that have the potential to alter Cho metabolism (e.g., methotrexate);
- history of hepatic, renal, or other chronic systemic disease.
- subjects with liver abnormalities (e.g.cysts) as determined by ultrasound
- current smokers
- consume \>2 alcoholic beverages/d or \>14/wk
- substance abusers or drug addicted
- eating unusual diet that would interfere with the study
- food allergies, (e.g., soy) or any problems with eating all foods on required study diet
- using Cho-containing dietary supplements
- women who are breastfeeding, pregnant, or plan to become pregnant due to potential risk to fetus/child of low choline diet
- performing intense exercise of more than 1 hour a day or other intense muscle building exercise (such as weightlifting beyond low weight repetitions)
- Actively participating in other research study where required to exercise or ingest any food, medicine, or supplement in any manner
- claustrophobia
- has a cardiac pacemaker, artificial heart valve, metal plate, pin, or other metallic implant, intrauterine device, insulin or other drug pump, aneurysm clips, previous gunshot wound, cochlear implant or other implantable hearing device, employment history as a metalworker, or permanent cosmetic tattoos (eyeliner, eyebrow)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
UNC Chapel Hill Nutrition Research Institute
Kannapolis, North Carolina, 28081, United States
Study Officials
- PRINCIPAL INVESTIGATOR
Steven H Zeisel, MD, PhD
University of North Carolina, Chapel Hill
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Participant dietary arm assignment is randomized by a randomization plan created by the study coordinator at www.randomization.com. Each of the 3 hormonal related demographic groups (male, premenopausal females, and postmenopausal females) will have a list of the same order of diets created by the randomizer. Each participant will be assigned upon entry into the study into the next open diet for their group as ordered by the randomizer. No one collecting or processing data will be informed of the choline levels the participant is experiencing in their dietary arms at any given time to attempt to eliminate bias and ensure appropriate data collection. All staff who interact with participants or who are handling samples/data, will not be informed of the code linking dietary choline levels to diet order.
- Purpose
- SCREENING
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 19, 2017
First Posted
July 31, 2017
Study Start
February 15, 2018
Primary Completion
October 18, 2018
Study Completion
October 18, 2018
Last Updated
December 3, 2019
Record last verified: 2019-12
Data Sharing
- IPD Sharing
- Will not share