The EXPLAIN Study: Exploring Plant-Based Meat Analogues for Their Impact on Health

Blood Pressure Clinical Trial

— EXPLAIN  

Official title:

The EXPLAIN Study: Exploring Plant-Based Meat Analogues for Their Impact on Health

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06370936
• Other study ID #: NL84824.091.23
• Secondary ID: NL84824.091.23
• Status: Recruiting
• Phase: N/A
• Start date: April 2024
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Wageningen University
• Contact: Roos van 't Spijker, MSc
• Phone: +31 (0) 317 484 882
• Email: roos.vantspijker[@]wur.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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.]

Related Conditions & MeSH terms

• Blood Pressure
• Cardiometabolic Health

Intervention

Other:
• Standardized diet with commercially available animal meats (comparator products)
Fully controlled standardized diet with commercially available meats from animal origin. Fully controlled means that all food products 8-week intervention will be provided by the HNRU at Wageningen University. The standardized diet is designed to maintain body weight, and follows the average nutritional pattern of middle-aged men and women in the Netherlands, while taking individual habitual energy intake into account. The diet will have the same dietary composition for each person and energy intake will be based on the energy requirements of an individual. The diet is the same for both intervention periods, except for the origin of meat products: PBMAs versus meat of animal origin.
• Standardized diet with commercially available PBMAs (intervention products)
Fully controlled standardized diet with commercially available Plant-Based Meat Analogues (PBMAs). Fully controlled means that all food products 8-week intervention will be provided by the HNRU at Wageningen University. The standardized diet is designed to maintain body weight, and follows the average nutritional pattern of middle-aged men and women in the Netherlands, while taking individual habitual energy intake into account. The diet will have the same dietary composition for each person and energy intake will be based on the energy requirements of an individual. The diet is the same for both intervention periods, except for the origin of meat products: PBMAs versus meat of animal origin.

Locations

Country	Name	City	State
Netherlands	Wageningen University, Division of Human Nutrition	Wageningen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Wageningen University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body composition	Body composition as measured by DEXA (Dual Energy X-ray Absorptiometry).	Baseline
Other	Genetic variation	Single Nucleotide Polymorphisms (SNPs) in genes relevant for metabolism and responses to food, collected using a mouth swab and/or buffycoat.	Baseline
Other	Oral glucose tolerance test (OGTT)	A 6-point OGTT measuring fasting and postprandial glucose and insulin responses. At t=0, 15, 30, 45, 60, 90, and 120 minutes, blood will be collected to measure plasma glucose and insulin concentrations. At t=0, HbA1c concentrations will also be determined. This measurement is only for participants with veins suitable for a Venflon catheter.	Baseline
Other	Habitual dietary intake	Habitual dietary intake assessment with a food frequency questionnaire (FFQ).	Baseline
Other	Perceived stress	Perceived stress of participant over past month as measured with the Perceived Stress Scale (PSS-10)	Baseline
Other	Chronotype assessment	Chronotype assessment of participant with reduced Morning-Eveningness Questionnaire (rMEQ)	Baseline
Other	Sleeping habits	Sleeping habits of participants over the past month as measured using the Pittsburgh Sleep Quality Index (PSQI).	Baseline
Other	Self reported habitual meat and PBMA consumption	Habitual dietary meat and PBMA consumption assessment using a questionnaire.	3 times during trial. At baseline and 2 times during 10-week washout period.
Other	24-hour dietary recall	24-hour dietary recall done using the Traqq mobile phone application.	6 times during the 10-week washout period
Other	Home environment microbiome composition	Microbiome composition on electrostatic dust collectors (EDC) that are placed in participants home for 2 consecutive weeks accompanied with regarding geographic location and placement of EDC.	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)
Primary	Systolic blood pressure	Systolic blood pressure as measured with in-clinic blood pressure measurements	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	Diastolic blood pressure	Diastolic blood pressure as measured with in-clinic blood pressure measurements	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	Home systolic blood pressure	Systolic blood pressure as measured by participant at-home	Twice daily for 16 weeks total (both 8-week interventions)
Secondary	Home diastolic blood pressure	Diastolic blood pressure as measured by participant at-home	Twice daily for 16 weeks total (both 8-week interventions)
Secondary	Home heart rate	Heart rate as measured by participant at-home with blood pressure monitor	Twice daily for 16 weeks total (both 8-week interventions)
Secondary	Fasting blood HbA1c levels	Fasting HbA1c concentration	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)
Secondary	Fasting blood glucose levels	Fasting glucose concentration	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)
Secondary	Fasting blood insulin levels	Fasting insulin concentration	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)
Secondary	Fasting blood lipid spectrum	Metabolomic analysis to determine all circulating blood lipids, including all cholesterol types, triglycerides and free fatty acids	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)
Secondary	Fasting blood metabolite profile	Fasting blood metabolome as determined by metabolomics.	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)
Secondary	Fasting blood proteomic profile	Proteomic analysis of fasting blood, incorporating an O-link panel, to determine circulating blood proteins, including protein biomarkers for inflammation such as cytokines.	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)
Secondary	Fasting blood cell transcriptomic profile	Analysis of blood cells using transcriptomics to determine the blood transcriptome.	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)
Secondary	Fasting blood nutritional status	Circulating vitamins and minerals related to meat and plant-based meat intake, including important circulating vitamins such as vitamins B6, B12, and D, and minerals such as markers of iron status, zinc, magnesium, and calcium.	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)
Secondary	Blood immune markers	Blood immune- and immune-metabolism markers. This includes immune-related proteins including cytokines.	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)
Secondary	Blood immune cell populations	Blood (immune) cell subpopulations. This compromises of whole blood CD45+ cell subset abundance such as abundance of T-lymphocytes and B-lymphocytes.	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)
Secondary	Metabolites in 24-hour urine	Metabolomic analysis of urine collected over 24 hours, including markers for sodium excretion, urea nitrogen excretion, kidney function and consumption of (plant-based) meat, pH, and volume of urine.	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)
Secondary	Interstitial glucose profile	Interstitial glucose concentrations, as measured by continuous glucose monitoring.	4 weeks during trial, 2 continuous weeks per 8-week intervention
Secondary	Physical activity	Continuous physical activity levels, measured by the Actigraph accelerometer wGT3X-BT (ActiGraph, Pensacola, USA)	4 weeks during trial, 2 continuous weeks per 8-week intervention
Secondary	Fecal microbiome composition	Microbiome composition in the feces.	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
Secondary	Fasting and postprandial circulating metabolites with a high fat mixed meal (HFMM) challenge	Circulating fasting and postprandial metabolites upon a high-fat mixed meal (HFMM). At t=0, 30, 60, 90, 120, 180, and 240 minutes after the consumption of the HFMM blood is collected. This measurement is only for participants with veins suitable for a Venflon catheter.	2 times during the trial. 1 time at the end of each 8 week-intervention.
Secondary	Oral microbiome composition	Microbiome composition in saliva.	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)
Secondary	Microbiome metabolites	Microbial metabolites of interest, such as SCFAs will be measured using high-performance liquid chromatography (HPLC).	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
Secondary	Microbiome functionality	Microbiome functionality and genetic composition is assessed using batch-fermentation.	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
Secondary	Self-reported gastro-intestinal symptoms	Gastro-intestinal symptoms as measured using the GSRS questionnaire (gastro-intestinal rating scale). The GSRS contains five scales: reflux syndrome, abdominal pain, constipation syndrome, diarrhoea syndrome and indigestion syndrome. Scores between 1-7. Low scores indicated absence or mild presence of symptoms, high scores indicated heavy presence of symptoms.	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
Secondary	Self-reported constipation	Gastro-intestinal obstipation symptoms as measured using the PAC-SYM questionnaire (Patient Assessment of Constipation Symptoms). Scores between 1-4. Low scores indicated absence or mild presence of symptoms, high scores indicated heavy presence of symptoms.	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
Secondary	Self-reported stool consistency and frequency	Self-reported stool consistency and frequency by using the Bristol Stool Chart (BSC) (scores between 1-7). Low scores indicate constipation and high scores diarrhea. Scores of 3-4 indicate a 'normal' stool.	18 times during trial. Done 1 time before each 8-week intervention and weekly during 8-week intervention.
Secondary	Gastro-intestinal transit time	Transit time measured using the blue dye method	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)
Secondary	Self reported product-specific attitude towards meat and PBMAs	Self-reported product-specific attitude towards meat and PBMAs as measured using a questionnaire. Scores between 1-7. Low scores indicate a negative attitude toward the product, and high scores indicate a positive attitude toward the product.	6 times during trial. 3 times per 8-week intervention, during CGM (continuous glucose monitor) wearing period.
Secondary	Self reported meal-specific satiety with meat and PBMAs	Self reported meal-specific satiety with meat and PBMAs measured using a questionnaire. The Visual Analogue Scale (VAS) is used for questions about satiety and Likert scale is used to assess the intensity of product attributes. Low scores indicate low liking/experience, and high scores indicate high liking/experience.	6 times during trial. 3 times per 8-week intervention, during CGM (continuous glucose monitor) wearing period.
Secondary	Self-reported general attitude toward meat and PBMAs	Self-reported general attitude toward meat and PBMAs as measured using a questionnaire. Scores between 1-7. Low scores indicate a negative general attitude and high scores indicate a positive general attitude	10 times during trial. 5 times per 8-week intervention (before intervention, week 1,2,4 and 8).