NutrImmune: Precision Nutrition to Improve Immunity in Individuals With Obesity

Institut National de la Santé Et de la Recherche Médicale, France

Status: Not yet enrolling

Conditions: Obesity (BMI>30); Low-grade Inflammation; Immune Abnormalities

Treatments: Other: Mixed test meal; Other: Balanced-immunity diet; Behavioral: Questionnaires; Other: Caloric restriction; Biological: Biological sampling

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07850206

C25-106

Details and patient eligibility

About

Obesity is a complex health condition defined by the World Health Organization (WHO) as an excess of body weight that may be harmful to health. It leads to other diseases such as type 2 diabetes or cardiovascular diseases, commonly referred to as "co-morbidities." Among these, it is known that obesity increases the risk of developing infectious diseases and of these diseases progressing to severe stages.

During the COVID-19 pandemic and the 2009 H1N1 influenza epidemic, a rise in severe infection cases was observed in people with obesity. A part of people with obesity exhibits certain markers on the surface of their immune cells, which are known to cause immunosuppression when present in high numbers, thus increasing the risk of developing infectious diseases.

Investigator teams found that after bariatric surgery and a calorie-restricted diet for weight loss, patients with obesity can improve the levels of these immunity-related markers. Moreover, the choice of foods consumed contributes to strengthening the immune system and immune functions of individuals, both directly by influencing inflammation and indirectly through the microbiota. However, to date, there are no dietary recommendations specifically designed to help people with obesity improve their immune response.

Therefore, this study aims to compare different dietary recommendations intended to improve immune status, with or without calorie restriction, during 3 months, in individuals with obesity (BMI ≥ 30 kg/m²) and impaired immunity. Over 6 months (3 months of nutritional intervention and 3 months of follow-up), investigators will collect extensive information through biological samples, measurements and questionnaires to compare the different dietary interventions studied and to understand the mechanisms behind the results obtained.

Full description

Beyond its metabolic consequences, obesity is associated with an increased risk of severe infectious diseases. Indeed, Obesity would be associated with immune remodeling, reduced microbial diversity, gut barrier dysfunction, and increased pro-inflammatory microbial species. These alterations can promote systemic inflammation and metabolic endotoxemia. Moreover, immune checkpoints, including the PD-1/PD-L1 pathway, are important regulators of immune responses and may also contribute to immune dysregulation in obesity.

Diet represents an important modulator of inflammation and immunity. The microbiome and the glycome may further mediate the effects of diet on immune function. Changes in microbial composition and host glycosylation can influence immune signaling and the activity of immune checkpoints.

Overall, the diet-microbiome-glycome axis may represent a key determinant of immune homeostasis in obesity. However, the effects of specific diets and nutrients on immune checkpoints remain insufficiently understood and require further clinical investigation.

In this clinical study, the investigator teams hypothesize that a nutritional intervention based on personalized dietary recommendations will improve the responses of markers associated with immunity (reduction in CD4+ cells and in the expression of immune checkpoint proteins on T cells, particularly PD-1) in individuals with obesity. The effects on immunity are thought to be mediated by changes in the gut microbiota and potentially by the immunoglycome, which should simultaneously lead to improvements in cardiometabolic health markers. These markers will also be monitored during this study.

The Nutrimmune clinical study is a controlled, randomized, open-label, parallel-group (3-arm), multicenter.

The investigators will recruit 168 volunteers (men or women) with moderate obesity (BMI between 30 and 40 kg/m²), aged 40 to 70 and at immune and metabolic inflammatory risk (hsCRP above 3 mg/L and dietary inflammatory index (E-DII)>0).

The intervention will consist of providing personalized nutritional advice through an app (called TOUVA developed by a private collaborator), which will offer participants appropriate meal plans each week. The nutritional advice will depend on the study arm to which the participant has been randomized.

Three nutritional interventions will be tested in parallel in this study:

• The Balanced-Immunity diet with calorie restriction (BI-CR),
• The Balanced-Immunity diet without calorie restriction (BI),
• The standard diet with calorie restriction (STD-CR)

During the study, participants will be seen for the first time during a screening visit, followed by three metabolic assessment visits: before starting the intervention, at 3 months into the nutritional intervention, and 3 months after the end of the intervention.

The primary endpoint will be the change in the percentage of CD4⁺ T cells expressing the immune checkpoint protein (ICP) PD-1 in PBMCs, measured from baseline to 3 months (end of the nutritional intervention).

The secondary endpoints included : immune and inflammatory phenotypes, microbiome and molecular mechanisms, cardiometabolic and physiological parameters, lifestyle and eating behaviour chang and acceptability, adherence and usability to the nutritional intervention.

This study would help advance scientific understanding of how dietary and personalized interventions can help improve markers associated with immunity in people with obesity and impaired immunity. In the public health goal to improve the care of people with obesity and impaired immunity.

Enrollment: 168 estimated patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 30≤BMI<40 kg/m2

• Waist circumference ≥80 cm for women and ≥94 cm for men

• Low-grade inflammatory status, defined as:

  • High-sensitive CRP (hsCRP) ≥ 3 mg/L
  • Low diet quality: E-DII > 0, indicating a pro-inflammatory dietary potential

• Affiliation with a social security scheme or beneficiary of such a scheme;

• Effective contraception for women with ability to have children

• Stable weight for at least 3 months (+/- 5% of total body weight)

• In the opinion of the investigator, the subject has adequate support to comply with the entire study requirements as described in the protocol (i.e. ability to move to and from trial site, to understand and fill in the questionnaires, use the app; attend the scheduled visits, full understanding of the protocol)

• Do not follow an exclusive diet (i.e. vegan, vegetarian, or diet without gluten or lactose)

• Living at maximum 1 hour from clinical trial site

• Willingness to not change physical activity level for the whole duration of the study.

• Willingness not to perform any other weight-loss approaches.

• Agreement to adhere to Lifestyle Considerations throughout study duration

• For women of childbearing potential, a negative urinary pregnancy test is required

General non-inclusion criteria:

• Persons subject to a safeguard of justice measure
• Persons without valid health certificate(s) in case of governmental measures in exceptional epidemic situations
• Persons under legal protection (guardianship, curatorship)
• Persons unable to use the study applications after a brief introduction or no access to a mobile phone or tablet with Bluetooth and internet access;
• Persons with devices with previous iOS or Android operating systems that cannot run the applications, given that use of the IPICS-app (TOUVA) is necessary for the study;
• Persons without a freezer and/or reluctant to store biological samples inside;
• Tobacco (or vaping equivalent) consumption > 5 cigarettes per day.
• Pregnancy or breastfeeding in women of childbearing potential
• Alcohol consumption exceeding 30g alcohol/day
• Claustrophobia for indirect calorimetry.
• Needle or blood phobia

Medical non-inclusion criteria:

• Usage in past 3 months : Antibiotics, Probiotics, Prebiotics, Systemic corticosteroids, Immunosuppressives

• Laxative usage in past 2 months

• PPI (Proton pomp inhibitor) usage in past 2 days

• Conditions that alter both inflammatory and immune profile and induce biases in results interpretation

  • Uncontrolled thyroid disease, history of musculoskeletal, autoimmune, or neurological disease, as well as abnormal kidney and liver function tests (>2 times upper reference range limit)
  • Presence of active chronic inflammatory disease, autoimmune disease requiring immunomodulatory treatment, known immunodeficiency, active malignancy, active chronic infection, or ongoing immunosuppressive treatment likely to significantly alter the immune parameters under investigation.
  • Presence of type 2 diabetes or uncontrolled cardiovascular disease (Stable obesity-related comorbidities, including hypertension, dyslipidemia, and stable cardiovascular disease, are not considered exclusion criteria).
  • Major mental disorders
  • Severe eating disorders based on detailed medical history, clinical examination and expertise of the investigating physician, trained in nutrition.
  • The use of medication or physical conditions interfering with the study outcomes, at the discretion of the investigating physician
  • Infectious episode in the month prior to inclusion
  • Allergy or intolerance to any of the components of the study devices and products
  • No contraindications to taking oral nutritional supplements, such as severe swallowing disorders or impaired consciousness, and non-functional digestive tract

Exclusion criteria

• Health conditions or treatments interfering with the protocol outcomes or procedure, depending on the situation, postponement of visits may be considered at the discretion of the physicians investigators;
• Withdrawal of consent
• Appearance of a non-inclusion criterion; depending on the situation, postponement of visits may be considered at the discretion of the investigating physicians;
• Lost to follow-up

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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168 participants in 3 patient groups

Balanced-Immunity without caloric restriction

Experimental group

Description:

The intervention will consist of providing personalized nutritional advice through an app called TOUVA, which will offer participants appropriate meal plans (according to their needs, food preferences and usual food consumption) each week during 3 months. The generated menu is based on food group distribution of the EAT- Lancet diet, except for oily fish, which will be set at two servings per week to ensure adequate omega-3 intake.

Treatment:

Biological: Biological sampling

Other: Balanced-immunity diet

Behavioral: Questionnaires

Other: Mixed test meal

Balanced-Immunity with caloric restriction

Experimental group

Description:

Description: The intervention will consist of providing personalized nutritional advice through an app called TOUVA, which will offer participants appropriate meal plans (according to their needs, food preferences and usual food consumption) with a caloric restriction of 500 kcal/days (based on the evaluation of total energy requirements), each week during 3 months. The generated menu is based on food group distribution of the EAT- Lancet diet, except for oily fish, which will be set at two servings per week to ensure adequate omega-3 intake.

Treatment:

Biological: Biological sampling

Other: Caloric restriction

Other: Balanced-immunity diet

Behavioral: Questionnaires

Other: Mixed test meal

Standard diet with caloric restriction

Experimental group

Description:

The intervention will consist of providing personalized nutritional advice through an app called TOUVA, which will offer participants appropriate meal plans, according to their needs, food preferences and usual food habits, each week during 3 months. The generated menu has a reduction of 500 kcal/day (based on the evaluation of total energy requirements). The calories reduction will be proportional across all food groups, except for fruits and vegetables, for which intake should remain unchanged.

Treatment:

Biological: Biological sampling

Other: Caloric restriction

Behavioral: Questionnaires

Other: Mixed test meal