ISRCTN - ISRCTN63745549: A new way to develop a smart personal nutrition system

Plain English Summary

Background and study aims
Since preventing chronic diseases is currently a major concern and one of the UN Sustainable Development Goals, changing the gut microbiome (microorganisms) through the diet has been drawing much interest. There is where Stance4Health comes in, building a mathematical algorithm able to predict gut microbial behaviour in response to a specific diet and vice versa. The gut microbiota has a strong influence on human health and can be modified by diet. Intestinal bacterial communities are diverse and vary from person to person but are endowed with substantial stability over time within an individual and share a high degree of functional capabilities across healthy individuals. Environment, lifestyle and diet are the critical factors determining the intestinal microbiota while genetics seems to play a lesser role. Dietary effects on the intestinal microbiota can occur in short and long time frames. A large intake of energy and nutrients can induce bacterial blooms in the human gut within a short time frame but long-term dietary patterns seem to be responsible for the gene and species richness of the gut microbiota. Stance4Health will develop a complete Smart Personalised Nutrition (SPN) service based on the use of mobile technologies (a nutritional app) as well as tailored food production that will optimize the gut microbiota and long-term consumer engagement.

Who can participate?
Normal weight and overweight healthy adults aged 20 - 65 years, and four groups of children aged 5-11 years: normal weight, overweight, with celiac disease and with a food allergy

What does the study involve?
Participants will be assigned to one of two levels of intervention and further divided into “control” and “treated” groups.
The nutritional app i-Diet will give participants specific advice about nutrition and lifestyle according to their dietary needs, either taking or not into account gut microbiota composition for the treated or the control group, respectively. The nutritional app will suggest a complete menu, which participants can modify and the app will recalculate the menu. In this way i-Diet will allow researchers to obtain the nutritional information of the food eaten by users.
Participants will learn to use i-Diet (through instruction/training) and will include in the app their preferences about the number of meals per day, the number of dishes included in the main meals and the desired portion size (from the photographs database), as well as their favourite and disliked recipes, so that the app will adjust its suggestions to improve user adherence and sustainability over time.
After a 2-week run-in period, the participants will be randomly assigned to a 12-week intervention with two different levels of personalised nutrition: Level 1 will involve the use of the i-Diet software and the analysis of gut microbiota and metabolites. Level 2 will involve the use of the i-Diet app and analysis of gut microbiota and metabolites, plus the use of a wearable band and the intake of placebo (control group) or personalised foods enriched in tannins (treated group). The wearable will be used to record physical activity, sleeping hours, body mass index, and body composition. In the case of personalised foods, they will be produced and distributed in a customised way for each individual, including different types and levels of tannin extracts.
There will be clinical evaluations at the beginning and at the end of the interventions to measure blood pressure, gut microbiota, short-chain fatty acids (SCFAs) and bile acid levels in faeces, previous diseases, height, weight, waist circumference, fat mass, muscle mass, dietary, lifestyle (smoking habits, physical activity and sleep patterns), and socioeconomic status.

What are the possible benefits and risks of participating?
Participants will receive for free the nutritional app i-Diet, fortified foods or supplements, and a wearable band.

Where is the study run from?
The Stance4Health consortium consists of 19 partners from eight European countries (Spain, Germany, Denmark, Romania, Italy, Greece, Belgium, UK). The nutritional intervention will be performed in Germany, Greece and Spain.

When is the study starting and how long is it expected to run for?
December 2017 to March 2023

Who is funding the study?
European Union Horizon 2020

Who is the main contact?
Prof. José Ángel Rufián-Henares
jarufian@ugr.es

Study website

https://www.stance4health.com/index.html

https://orcid.org/0000-0002-1428-4353

Contact details

Dpto. Nutrición
Facultad de Farmacia
Campus de Cartuja S/N
Granada
18071
Spain
+34 (0)958 240749
jarufian@ugr.es

Additional identifiers

EudraCT/CTIS number

Nil known

IRAS number

ClinicalTrials.gov number

Nil known

Protocol/serial number

816303 (Project Number)

Study information

Scientific title

Smart Technologies for personAlised Nutrition and Consumer Engagement (Stance4Health)

Acronym

Stance4Health

Study hypothesis

The Stance4Health project thanks to a nutritional intervention programme, aims to evaluate the efficacy of a smart personalised nutrition (SPN) service in modifying gut microbiota (GM) composition and improving consumer empowerment through technology adoption.

Ethics approval(s)

1. Approved 10/06/2020, Ethics Committees for Investigation of the University of Granada (Cuesta del Hospicio S/N, 18071, Granada, Spain; +33 (0)958 246180; fovalle@ugr.es), ref: 1080/CEIH/2020
2. Approved 04/06/2020, Scientific Committee of the University Hospital of Ioannina (Stavrou Niarhou, 45500 - Ioannina, Greece; +30 (0)26510 99519; epsymb@uhi.gr), ref: protocol number 382, decision number 10/3-6-2020
3. Approved 22/07/2020, Ethics Committee University Hospital of Patras (Rion-Patras, 26504, Greece; +30 (0)2613603101; kefiap@pgnp.gr), ref: 261/16-6-20
4. Approved 14/04/2020, Epistimoniko Symvoulio - Attikon Hospital (Rimini 1, Athens 12462, Greece; +30 (0)210 5831000; greps@attikonhospital.gr), ref: 159/3-4-2020

Study design

Multicenter single-blind placebo-controlled randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Study setting(s)

Community

Study type

Prevention

Patient information sheet

https://www.stance4health.com/theproject.html

Condition

Nutrition and lifestyle

Intervention

The personalised nutrition intervention will be developed through a Smart Personalised Nutrition (SPN) service using a randomised controlled trial targeting gut microbiota (GM) composition and functionality, consumer empowerment through technology adoption and long-lasting adoption of healthy and sustainable diets.

The clinical study will be conducted in a single-blind randomised manner in two different study populations:

Study population 1 (normal-weight and overweight adults)

Individuals from Germany and Spain will be assigned to one of two levels of intervention and further divided into “control” and “treated” groups. The random allocation sequence will be provided and managed by an investigator who will not take part in the participants’ recruitment.
The study will use a parallel design and will be characterised by the use of the nutritional app i-Diet. i-Diet will give participants specific advice about nutrition and lifestyle (taking or not into account gut microbiota composition, respectively for treated or control group) according to their dietary needs. The nutritional app will suggest a complete menu, which participants can modify and the app will recalculate the menu. In this way i-Diet will allow researchers to obtain the nutritional information of the food ingested by users.
Participants will learn to use i-Diet (through instruction/training) and will include in the app their preferences about the number of meals per day, the number of dishes included in the main meals and the desired portion size (from the photographs database), as well as their favourite and disliked recipes, so that the app will adjust its suggestions to improve user adherence and sustainability over time.
After a 2-week run-in period, the eligible participants will be randomly assigned to a 12-week intervention with two different levels of personalised nutrition: Level 1 (entry level, n = 50 Spanish and 50 German subjects in the control and treated groups; total n = 200) will consist of the use of the i-Diet software and the analysis of gut microbiota and metabolites. Level 2 (advanced level, n = 50 Spanish and 50 German subjects in the control and treated groups; total n = 200) will consist of the use of the i-Diet app and the analysis of gut microbiota and metabolites (as in the entry level), plus the use of a wearable band, and the intake of placebo (control group) or personalised foods enriched in tannins (treated group). The wearable will be used to record physical activity, sleeping hours, body mass index, and body composition. In the case of personalised foods, they will be produced and distributed in a customised way for each individual, including different types and levels of tannin extracts, looking for a deeper modulation of the gut microbiota composition and functionality. All data recorded in i-Diet and wearable band and the results of the analysis will be recorded in specific databases.
Before the intervention, there will be two clinical evaluations of the study population: at the beginning (T0) and at the end of the interventions (T1). Both at T0 and T1 health (blood pressure, gut microbiota composition and gene expression, metabolomics profile from gut microbiota, short-chain fatty acids (SCFAs) and bile acid levels in faeces, previous pathologies), anthropometric (height, weight, waist circumference, fat mass, muscle mass), dietary, lifestyle (smoking habits, physical activity and sleep patterns), and socioeconomic status information will be collected in specific data-sheets.

Study population 2 (Greek children with obesity (a), with gluten disease (b), non-cow’s milk consumers (c), normal weight (d))
Updated 22/07/2022: (Greek children with obesity (a), with gluten-related disorders (b), with allergy/intolerance to cow’s milk (c), normal weight (d))

Individuals in each of the aforementioned (a, b, c, and d) groups will be assigned to the “control” and “treated” subgroups. The random allocation sequence will be provided and managed by an investigator who will not take part in the participants’ recruitment. i-Diet will provide nutritional information on food (including branded food and fast food) so that users can make better choices in retailers, and specific advice about nutrition and lifestyle (taking or not into account gut microbiota composition respectively for the treated or control group). i-Diet will be also used as a novel personalised nutrition tool. To do so, participants and/or their parents/carers will learn to use the i-Diet app (through instructions/training) in order to indicate to the app which of the suggested meals the user has finally eaten and which ones he/she has substituted (and with which recipe he/she has replaced it), and selecting the corresponding serving size (portion) from the photographs database.
After a 4-week run-in period, the eligible participants will be randomly assigned to a 12-week intervention with two different levels of personalised nutrition. They will all use the i-Diet software and undergo analysis of gut microbiota and metabolites. However, those in the “treated” subgroups will also receive personalised fortified foods (tannin extracts, looking for a deeper modulation of the gut microbiota composition and functionality) whereas the “control” group will receive placebo. All data recorded in the i-Diet and the results of the analysis will be recorded in specific databases. Intervention procedures will be pre-tested in at least five participants.
There will be two clinical evaluations of the study population: at the beginning (T0) and at the end of the interventions (T1). Both at T0 and T1 health (blood pressure, gut microbiota composition and gene expression, metabolomics profile from gut microbiota, SCFAs and bile acids levels in faeces), anthropometric (height, weight, waist circumference, fat mass, muscle mass), dietary, lifestyle (physical activity and sleep patterns), and the family’s socio-economic status information will be collected in specific data-sheets.

Intervention type

Mixed

Primary outcome measure

1. Variation in alpha diversity determined by 16S gene-targeted sequencing at baseline and 12 weeks
2. Consumer empowerment through technology adoption and long-lasting adoption of healthy and sustainable diet, measured using questionnaire and Food Frequency Questionnaire (FFQ) at baseline, 12 and 24 weeks

Secondary outcome measures

1. Food intake measured using FFQ and nutritional app at baseline and 12 weeks
2. Body weight self-measured using a scale at baseline, 4, 8, 12, 24 weeks
3. Blood pressure self-measured using a sphygmomanometer at baseline, 4, 8, 12, 24 weeks
4. Body composition, physical activity levels and sleep duration measured using a wearable band at baseline, 4, 8, 12, 24 weeks
5. Short-chain fatty acids and secondary bile acids in faeces measured using targeted metabolomics by means of mass spectrometry at baseline and 12 weeks
6. Urine metabolomics measured using an in vitro metabolomics diagnostic test at baseline and 12 weeks

Overall study start date

04/12/2017

Overall study end date

31/03/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Study population 1 (normal-weight and overweight adults):
1. Age 20 - 65 years
2. Apparently healthy
3. BMI 20-28 kg/m²
4. Weight stable
5. Use of smartphone
6. Internet connection

Study population 2:
1. BMI ≥95 percentile for age, gender and height, males 6-11 years, females 6-11 years
2. Diagnosed with celiac disease, aged 6-11 years, on elimination (gluten-free) diet and allergic to gluten (very few), on elimination (gluten-free) diet
3. Age males 6-11-years, females 6-11 years and one of the following:
3.1. IgE-mediated milk allergy, on elimination diet from infancy
3.2. Lactose intolerance (symptoms plus breath hydrogen positive test)
3.3. Overgrown IgE-mediated milk allergy but current aversion for milk
3.4. Nondefinable phenotype (children who avoid milk but do not belong to any of the previous phenotypes)
4. BMI >5th and <85th percentile for age, gender, and height, age: males 6-11 years, females 6-11 years

Updated 22/07/2022:
Study population 2:
1. BMI ≥95 percentile for age, gender and height, males 5-11 years, females 5-11 years
2. Diagnosed with celiac disease, aged 5-11 years, on elimination (gluten-free) diet and allergic to gluten (very few), on elimination (gluten-free) diet
3. Age males 5-11 years, females 5-11 years and one of the following:
3.1. IgE-mediated milk allergy, on elimination diet from infancy
3.2. Lactose intolerance (symptoms plus breath hydrogen positive test)
3.3. Overgrown IgE-mediated milk allergy but current aversion for milk
3.4. Nondefinable phenotype (children who avoid milk but do not belong to any of the previous phenotypes)
4. BMI >5th and <85th percentile for age, gender, and height, age: males 5-11 years, females 5-11 years

Participant type(s)

Mixed

Age group

Mixed

Lower age limit

5 Years

Upper age limit

65 Years

Government

Website

https://www.isa.cnr.it

ROR

https://ror.org/0013zhk30

Funders

Funder type

Not defined

Funder name

European Commission

Alternative name(s)

European Union, Comisión Europea, Europäische Kommission, EU-Kommissionen, Euroopa Komisjoni, Ευρωπαϊκής Επιτροπής, Европейската комисия, Evropské komise, Commission européenne, Choimisiúin Eorpaigh, Europskoj komisiji, Commissione europea, La Commissione europea, Eiropas Komisiju, Europos Komisijos, Európai Bizottságról, Europese Commissie, Komisja Europejska, Comissão Europeia, Comisia Europeană, Európskej komisii, Evropski komisiji, Euroopan komission, Europeiska kommissionen, EC, EU

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

Results and Publications

Publication and dissemination plan

The results obtained will be published in peer-reviewed open access publications. At least four different publications will be published describing the general population data, nutritional modifications, effects over the gut microbiota composition-functionality, and food consumption.

Intention to publish date

30/09/2023

Individual participant data (IPD) sharing plan

The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. José Ángel Rufián-Henares (jarufian@ugr.es).

IPD sharing plan summary

Available on request

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article		19/05/2022	31/05/2022	Yes	No
Basic results	Spanish adults	06/09/2023	06/09/2023	No	No

Additional files

ISRCTN63745549_BasicResults_SpanishAdults_06Sep23.pdf Spanish adults

Editorial Notes

07/09/2023: Total final enrolment added. 06/09/2023: Basic results uploaded. 22/07/2022: The inclusion criteria and interventions were updated. 31/05/2022: The following changes were made to the trial record: 1. Publication reference added. 2. The recruitment end date was changed from 31/01/2022 to 31/12/2022. 3. The overall trial end date was changed from 31/05/2022 to 31/03/2023. 30/12/2021: The recruitment end date was changed from 31/12/2021 to 31/01/2022. 07/10/2021: Trial's existence confirmed by the Ethics Committees for Investigation of the University of Granada.