Choline and Cardiometabolic Health

Sponsor

Virginia Polytechnic Institute and State University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04764162

Collaborator

(none)

Enrollment

Location

Arms

23.5

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Risk Factor	Dietary Supplement: Choline capsule Dietary Supplement: Placebo capsule	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Double-blind, placebo-controlled, crossover designDouble-blind, placebo-controlled, crossover design

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Short Term Choline Supplementation and Cardiometabolic Health in Adults

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Choline supplementation Participants will consume 1000 mg of choline per day for 4 weeks.	Dietary Supplement: Choline capsule Participants will consume 1000 mg (2 x 500 mg) of choline bitartrate (over-the-counter supplement) for 28 consecutive days. They will continue to consume 1000 mg of choline bitartrate during the post-testing period.
Placebo Comparator: Placebo supplementation Participants will consume 1000 mg of placebo per day for 4 weeks.	Dietary Supplement: Placebo capsule Participants will consume 1000 mg (2 x 500 mg) of placebo (maltodextrin) for 28 consecutive days. They will continue to consume 1000 mg of placebo during the post-testing period.

Arm

Intervention/Treatment

Active Comparator: Choline supplementation

Participants will consume 1000 mg of choline per day for 4 weeks.

Dietary Supplement: Choline capsule

Participants will consume 1000 mg (2 x 500 mg) of choline bitartrate (over-the-counter supplement) for 28 consecutive days. They will continue to consume 1000 mg of choline bitartrate during the post-testing period.

Placebo Comparator: Placebo supplementation

Participants will consume 1000 mg of placebo per day for 4 weeks.

Dietary Supplement: Placebo capsule

Participants will consume 1000 mg (2 x 500 mg) of placebo (maltodextrin) for 28 consecutive days. They will continue to consume 1000 mg of placebo during the post-testing period.

Outcome Measures

Primary Outcome Measures

Change in Insulin Response after Supplementation [3-hour test in laboratory at 4 timepoints; baseline, week 4, week 6, and week 10]
Participants will complete a mixed meal tolerance test at baseline, after a 2-week washout, and immediately following each 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 mixed meal beverage (Ensure original®, 220 calories, 32 g carbohydrate, 6 g fat, and 9 g protein). Blood will be collected in small amounts (less than one half teaspoon) at eight timepoints over a three-hour period. This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).

Secondary Outcome Measures

Change in 24-hour Area Under the Curve for Glucose Levels after Supplementation [4-day measurement during free living]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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

Exclusion Criteria:

BMI > 35 kg/m2
Smoking
Pregnant or plans of becoming pregnant
Vegetarian or Vegan
Changed dieatry patterns within the last month
Diabetes (or use of diabetes medications) or unstable heart disease
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