Clinical trial NCT05071196: Facilitated Vegan Diet on Cardiometabolic Endpoints and Trimethylamine N-oxide
Official title: Impact of Facilitated Vegan Diet on Cardiometabolic Endpoints and Trimethylamine N-oxide
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cardiometabolic Risk Factors
Keywords: Vegan
boxed meal kit
trimethylamine N-oxide
cardiometabolic
Lead sponsor: David Grant U.S. Air Force Medical Center
Sponsor class: FED
First posted: 2021-10-08
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, controlled, prospective clinical trial
Primary purpose: PREVENTION

Brief summary: Vegan meal kit delivery offers consumer convenience and has shown benefit in cardiometabolic parameters such as low-density lipoprotein cholesterol (LDL-c) and weight. The purpose of this study is to evaluate the impact of meal kit facilitated vegan diet on LDL-c and trimethylamine N-oxide (TMAO) when compared to an omnivorous diet control.

Detailed description: This study will compare the impact of a vegan diet to a non-vegan diet, when provided with meal kits in participants who are overweight.

A vegan diet includes foods that come from plants and excludes foods that come from animals like meat, dairy, and eggs. Dietary modifications such as adopting a vegan diet are associated with significant improvements in cardiometabolic parameters, making it one of the preferred treatment options for obesity and preventing associated health conditions. Meal kits are packages that include: a quick (\~30-45 minutes) and simple recipe, all the recipe's required ingredients, and are conveniently delivered to patient homes. In this study, a facilitated vegan diet is defined as a change from an omnivorous diet to a vegan diet with the aid of boxed vegan meal kit delivery. A facilitated vegan diet has shown LDL-c and weight improvements over continuing an omnivorous diet in a preliminary study.

TMAO, changes in gut microbiome, and compliance to dietary modification impact cardiovascular and overall health. TMAO is a diet dependent biomarker for CVD, as elevated TMAO levels are associated with a 62% increased risk of heart attack, stroke, or death. TMAO increases platelet hyperactivity, inflammation, and foam cell generation, all of which contribute to atherosclerosis and may explain the increased risk of CVD. Additionally, TMAO predicts risk of major adverse cardiovascular events independently of other cardiovascular risk factors.

Consumption of animal products elevate TMAO levels due to its abundance of TMAO precursors: choline and carnitine. Chronic dietary red meat was associated with increased TMAO levels over white meat and non-meat protein. One study found that consuming plant-based alternative meat products improved TMAO levels over a mostly red meat diet. Both study interventions replaced protein sources but did not remove animal products such as eggs and dairy, which have conflicting evidence relative to TMAO. This study intervention will have participants adopt a full vegan diet, eliminating animal products.

The gut microbiome plays a crucial role in converting dietary precursors into TMAO. TMAO levels post l-carnitine ingestion were significantly higher in patients on a long-term omnivorous diet vs patients on a long-term vegan or vegetarian diet. This suggests that the gut microbiome in a plant-based diet lowers the formation of TMAO via the diet. This study will explore changes in gut microbiome from a dietary intervention in relation to TMAO and explore if these changes are sustained after discontinuing a 4-week facilitated vegan diet. Additionally, changes in gut microbiome will be explored in relation to microbiota changes seen in other disease states such as anxiety, irritable bowel disease, and other inflammatory diseases.

The impact of dietary modifications on controlling obesity and associated health conditions has room for improvement. Dietary modifications have long been one of the preferred treatments in obesity and CVD prevention, yet the obesity rates continue to rise. One potential area of improvement is compliance to dietary modification. This study will explore changes in food group restricted free diet patterns after a 4-week vegan meal kit intervention.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* BMI ≥ 25kg/m\^2
* Consume ≥ 5 servings red meat per week
* Active duty military and Department of Defense (DoD) Beneficiaries with active Tricare insurance
* Willing and able to adopt a vegan or standard omnivorous diet for 4 weeks
* Willing and able to track meal patterns, nutritional intake, exercise activity, and adverse events for 13 weeks
* Willing and able to come to David Grant USAF Medical Center for 4 blood draws
* Able to receive weekly emails and receive and prepare meal kits

Exclusion Criteria:

* Currently on a vegetarian, vegan, or food-group restricted diet
* Currently taking or planning to initiate medications or supplements that significantly affect TMAO levels, carnitine, choline, or gut microbiome (Systemic antibiotics, antifungals, antivirals, antiparasitic, corticosteroids, methotrexate, cytokines, or immunosuppressive cytotoxic agents, laxatives, proton pump inhibitors, resveratrol, meldonium, or metformin)
* Currently consuming the following ≥ 2 times per week: probiotics/prebiotics, probiotic enhanced foods (eg. enhanced yogurt, kefir, kombucha), or energy drinks, multivitamins, or supplements with choline, carnitine, or betaine (Acceptable to consume: non-probiotic enhanced yogurts, energy drinks and multivitamins without choline, carnitine, or betaine)
* Participants will have the option to delay study start if they express interest in the study and have permanently discontinued one of the excluded diet, medication, or supplement listed previously within the past 4 weeks (minimum 4 week time between discontinuation of excluded item and study start)
* Clinically significant or unstable cardiovascular, gastrointestinal, hepatic, or renal disease states defined as requiring on-going changes to medication or medical management
* Consumption of smoking or chewing tobacco, or other nicotine-containing products for \>1 day per week
* Consumption of \>14 alcohol drinks per week
* Pregnant, breastfeeding, or plan to become pregnant

Primary outcomes:
measure: Change between intervention arms in baseline adjusted LDL-c at 4 weeks
timeFrame: 4 weeks
measure: Change between intervention arms in baseline adjusted TMAO at 4 weeks
timeFrame: 4 weeks
Secondary outcomes:
measure: Change between intervention arms in baseline adjusted LDL-c at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted LDL-c at 12 weeks
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted TMAO at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted TMAO at 12 weeks
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted lipid panel parameters at 4 weeks
timeFrame: 4 weeks
measure: Change between intervention arms in baseline adjusted lipid panel parameters at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted lipid panel parameters at 12 weeks
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted BMI at 4 weeks
timeFrame: 4 weeks
measure: Change between intervention arms in baseline adjusted BMI at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted BMI at 12 weeks
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted blood pressure at 4 weeks
timeFrame: 4 weeks
measure: Change between intervention arms in baseline adjusted blood pressure at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted blood pressure at 12 weeks
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted hemoglobin A1c at 4 weeks
timeFrame: 4 weeks
measure: Change between intervention arms in baseline adjusted hemoglobin A1c at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted hemoglobin A1c at 12 weeks
timeFrame: 12 weeks
Other outcomes:
measure: Difference between intervention arms in baseline adjusted gut microbiome at 4 weeks
timeFrame: 4 weeks
measure: Change between intervention arms in baseline adjusted gut microbiome at 8 weeks
timeFrame: 8 weeks
measure: Change between intervention arms in baseline adjusted gut microbiome at 12 weeks
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted complete blood count
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted serum C-reactive protein
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted serum high sensitivity C-reactive protein
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted serum vitamin B12 level
timeFrame: 12 weeks
measure: Change between intervention arms in baseline adjusted serum iron
timeFrame: 12 weeks
measure: Change in calorie intake
timeFrame: 12 weeks
measure: Change in meal patterns post vegan meal kit intervention
timeFrame: 12 weeks
Locations:
city: Travis Air Force Base
country: United States
facility: David Grant U.S. Air Force Medical Center
state: California
Study officials:
References:
citation: The Vegan Diet. National Health Service website. Updated Aug 2018. Accessed 10 Jan 2021.
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citation: Crimarco A, Springfield S, Petlura C, Streaty T, Cunanan K, Lee J, Fielding-Singh P, Carter MM, Topf MA, Wastyk HC, Sonnenburg ED, Sonnenburg JL, Gardner CD. A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood-Meat Eating Alternative Trial (SWAP-MEAT). Am J Clin Nutr. 2020 Nov 11;112(5):1188-1199. doi: 10.1093/ajcn/nqaa203.
citation: Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7.