Clinical trial NCT06370936: The EXPLAIN Study: Exploring Plant-Based Meat Analogues for Their Impact on Health
Official title: The EXPLAIN Study: Exploring Plant-Based Meat Analogues for Their Impact on Health
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Blood Pressure
Cardiometabolic Health
Keywords: Standardized diet
Plant based meat analogues
Blood pressure
Cardiometabolic health
Intestinal health
Microbiome
Animal meat
Lead sponsor: Wageningen University
Sponsor class: OTHER
First posted: 2024-04-17
Enrollment: 114
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will follow both an 8-week completely controlled dietary intervention followed by a 10-week washout period followed by another 8-week completely controlled dietary intervention.
Primary purpose: PREVENTION

Brief summary: Plant-based diets with little to no meat are considered healthy and sustainable by the general public. The increasingly popular plant-based meat analogues (PBMAs) allow consumers to easily decrease meat intake while maintaining their dietary patterns. However, scientific knowledge on the health impact of PBMAs on humans is currently very limited.

The primary objective of this clinical trial is to evaluate if and to what extent replacing all meat products in an average Dutch diet with currently commercially available PBMAs affects the systolic blood pressure of middle-aged men and women in a 2x8 week fully dietary controlled crossover intervention study. The secondary objectives are to assess the effect of this replacement of meat products with PBMAs on cardiometabolic health, gut microbiome, intestinal health, well-being, and underlying biological mechanisms.

114 men and women with a BMI of 23-40 kg/m2, aged 45-75 years will be included in the study. Participants will follow both an 8-week completely controlled diet in which all meats are of plant-based origin (PBMAs) and an 8-week diet in which all meats are of animal origin in randomized order with a 10-week wash-out period. Before the intervention starts, the participants will be characterized to describe them on anthropometrics, glucose tolerance and insulin sensitivity, genetics, sleep patterns, and stress levels. Before the start and at the end of each 8-week dietary intervention period, several measurements, including systolic blood pressure monitoring and secondary outcome measures will be done. Additionally, systolic and diastolic blood pressure will be monitored throughout the dietary interventions and a small quantity of parameters related to the secondary objectives will be measured.

Detailed description: Plant-based diets with little to no meat are considered healthy and sustainable by the general public. The increasingly popular plant-based meat analogues (PBMAs) allow consumers to easily decrease meat intake while maintaining their dietary patterns. PBMAs are designed to mimic the sensory and textural properties of meat and to replace animal protein with plant protein. Processing of plant-based ingredients is needed to achieve this, which potentially compromises the sustainability and health assets of PBMAs. One of the concerns with processing is that it results in relatively high salt levels in the products, which could affect the blood pressure of consumers. However, scientific knowledge on the health impact of PBMAs on humans is currently very limited. Therefore, a fully controlled dietary intervention with a standardized diet is needed to evaluate the health impact of commercially available PBMAs.

The primary objective is to evaluate if and to what extent replacing all meat products in an average Dutch diet with currently commercially available PBMAs affects the systolic blood pressure of middle-aged men and women in a 2x8 week fully dietary controlled crossover intervention study. The secondary objectives are to assess the effect of this replacement of meat products with PBMAs on cardiometabolic health, gut microbiome, and intestinal health, well-being, and underlying biological mechanisms. In addition, the investigators aim to study the relation between diet-specific responses (comparing PBMAs and meat products) and phenotype, including glucose responses and body composition.

The study compromises a randomized crossover fully controlled dietary intervention at Wageningen University which consists of 2x8 week interventions separated by a 10-week washout period. Before the intervention starts, the participants will be characterized to describe them on anthropometrics, glucose tolerance and insulin sensitivity, genetics, sleep patterns, and stress levels. Before the start and at the end of each 8-week dietary intervention period, several measurements, including systolic blood pressure monitoring and secondary outcome measures will be done. Additionally, systolic and diastolic blood pressure will be monitored throughout the dietary interventions and a small quantity of parameters related to the secondary objectives will be measured.

The study population consists of 114 men and women with a BMI of 23-40 kg/m2, aged 45-75 years, and weight stable (± \<3kg) for at least three months before inclusion. Participants will follow both an 8-week completely controlled diet in which all meats are of plant-based origin (PBMAs) and an 8-week diet in which all meats are of animal origin in randomized order with a 10-week wash-out period. Diets are fully controlled which implies that all foods and meals are provided to participants by the Human Nutrition Research Unit (HNRU) and are based on participants' habitual energy needs to maintain a stable body weight throughout the study. Except for PBMAs/meat, all other foods will be identical in both intervention diets. The composition of the diets is based on the Dutch National Food Consumption Survey. All food products provided, including the PBMAs, are commercially available.

The total study duration for a participant will be a little over \>6 months, including the 10-week washout. The total time that needs to be invested by participants in this study with visits and at-home measurements is 72 hours. Participants are restricted for a total of 16 weeks in their eating habits since they need to follow a fully standardized diet. Subjects will have their blood pressure measured at the HNRU and additionally will have to measure their blood pressure at home. In addition, subjects have to wear continuous glucose and physical activity monitors twice during the study for a total of approximately 28 days. During the characterization period, participants will visit the HNRU once or twice depending on participant preference. For the measurements before and at the end of each dietary intervention period, participants visit the HNRU three times per intervention period (one extra visit after for the HFMM), so six times total. Additionally, during the dietary intervention, participants will visit the Human Research Unit twice a week during dinner time.

Eligibility criteria: Inclusion Criteria:

* BMI of 23-40 kg/m2
* Age 45-75 years
* Willing to consume both meat and PBMAs
* Stable body weight (lost/gained ± \<3 kg over the last 3 months prior to inclusion)

Exclusion Criteria:

* Diseases or prior surgeries affecting the stomach, liver, kidneys or intestines (allowed i.e. appendectomy)
* Food allergies, intolerances (including lactose/gluten intolerance) for products used in the study design, and/or dietary restrictions interfering with the study (including special diets, vegetarians, and eating disorders)
* Cardiovascular diseases (e.g. heart failure. But hypertension up to 160 mmHg is allowed for inclusion as indicated by the research physician) or cancer (e.g. non-invasive skin cancer allowed)
* Anemia defined as Hb concentrations \<8.5 mmol/L for men and \<7.5 mmol/L for women
* Diagnosed with type 1 or type 2 diabetes
* Blood pressure \>160 mmHg\*
* Major mental disorders
* Drug-treated thyroid diseases (well-substituted hypothyroidism is allowed for inclusion)
* Diseases with a life expectation shorter than 5 years
* Regular use of/receiving medication interfering with research outcomes (as judged by research physician), such as the use of glucose-lowering drugs, insulin, use of medication that impacts gastric emptying, use of antipsychotics
* Starting or changing blood pressure medication type or dose during the study. (Continuation of blood pressure medication usage is allowed during the study)
* Use of anti-biotics over the last 3 months before the study start
* Dietary habits interfering with study design (vegan/vegetarian, ketogenic diet, etc.)
* Intention to change the intensity of exercise during the study period;
* Intention to lose weight during the study period
* Current smokers (including use of e-cigarettes)
* Use of soft and/or hard drugs (cannabis included)
* Abuse of alcohol (alcohol consumption defined as \>14 glasses (women) or \>21 glasses (men) of alcoholic beverages per week)
* Use of strong vitamins or other dietary supplements (e.g. iron- or B12-supplements, pre- or probiotics) expected to interfere with the study outcomes.
* Donated blood within 2 months prior to the screening
* Inability to comply with the study diet
* Being pregnant or lactating or planning to become pregnant
* Unable/unwilling to download a research application on the mobile phone
* Inability to understand study information and/or communicate with staff
* Inability/unwillingness to comply with staff instructions
* Displaying misbehavior towards other participants/staff
* Participation in another study that involves an intervention within two months prior to the intervention
* Working or doing a thesis/internship at the Division of Human Nutrition and Health or the Laboratory of Microbiology of Wageningen University.

\[\*Participants with a screening systolic blood pressure \>140 mmHg - ≤160 mmHg need written permission for participation without having (medical) treatment for the study period granted by their general practitioner after assessment of their cardiovascular risk. Participants within this screening range who cannot hand over written clearance from their general practitioner will be excluded from participation. Participants whose blood pressure has measured \>140 mmHg (systolic) or \>90 mmHg (diastolic) one or more times during the study, will receive a letter for referral to the general practitioner.\]

Primary outcomes:
measure: Systolic blood pressure
timeFrame: 12 times during the trial, 6 times per 8-week intervention (1 time before intervention period, then biweekly measurements, and 1 measurements in week 8 of 8-week intervention)
Secondary outcomes:
measure: Diastolic blood pressure
timeFrame: 12 times during the trial, 6 times per 8-week intervention (1 time before intervention period, then biweekly measurements, and 1 measurements in week 8 of 8-week intervention)
measure: Home systolic blood pressure
timeFrame: Twice daily for 16 weeks total (both 8-week interventions)
measure: Home diastolic blood pressure
timeFrame: Twice daily for 16 weeks total (both 8-week interventions)
measure: Home heart rate
timeFrame: Twice daily for 16 weeks total (both 8-week interventions)
measure: Fasting blood HbA1c levels
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood glucose levels
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood insulin levels
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood lipid spectrum
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood metabolite profile
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood proteomic profile
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood cell transcriptomic profile
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Fasting blood nutritional status
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Blood immune markers
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Blood immune cell populations
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Metabolites in 24-hour urine
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Interstitial glucose profile
timeFrame: 4 weeks during trial, 2 continuous weeks per 8-week intervention
measure: Physical activity
timeFrame: 4 weeks during trial, 2 continuous weeks per 8-week intervention
measure: Fecal microbiome composition
timeFrame: 18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
measure: Fasting and postprandial circulating metabolites with a high fat mixed meal (HFMM) challenge
timeFrame: 2 times during the trial. 1 time at the end of each 8 week-intervention.
measure: Oral microbiome composition
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Microbiome metabolites
timeFrame: 18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
measure: Microbiome functionality
timeFrame: 18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
measure: Self-reported gastro-intestinal symptoms
timeFrame: 18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
measure: Self-reported constipation
timeFrame: 18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
measure: Self-reported stool consistency and frequency
timeFrame: 18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
measure: Gastro-intestinal transit time
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
measure: Self reported product-specific attitude towards meat and PBMAs
timeFrame: 6 times during trial. 3 times per 8-week intervention, during CGM (continuous glucose monitor) wearing period.
measure: Self reported meal-specific satiety with meat and PBMAs
timeFrame: 6 times during trial. 3 times per 8-week intervention, during CGM (continuous glucose monitor) wearing period.
measure: Self-reported general attitude toward meat and PBMAs
timeFrame: 10 times during trial. 5 times per 8-week intervention (before intervention, week 1,2,4 and 8).
Other outcomes:
measure: Body composition
timeFrame: Baseline
measure: Genetic variation
timeFrame: Baseline
measure: Oral glucose tolerance test (OGTT)
timeFrame: Baseline
measure: Habitual dietary intake
timeFrame: Baseline
measure: Perceived stress
timeFrame: Baseline
measure: Chronotype assessment
timeFrame: Baseline
measure: Sleeping habits
timeFrame: Baseline
measure: Self reported habitual meat and PBMA consumption
timeFrame: 3 times during trial. At baseline and 2 times during 10-week washout period.
measure: 24-hour dietary recall
timeFrame: 6 times during the 10-week washout period
measure: Home environment microbiome composition
timeFrame: 4 times during the trial. 2 times per 8 week-intervention (1 time before intervention and 1 time during week 8 of 8-week intervention)
Locations:
city: Wageningen
country: Netherlands
facility: Wageningen University, Division of Human Nutrition
state: Gelderland
Study officials:
affiliation: Wageningen University and Research
name: Lydia Afman
role: PRINCIPAL_INVESTIGATOR
References: