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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:
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
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Inclusion criteria
30≤BMI<40 kg/m2
Waist circumference ≥80 cm for women and ≥94 cm for men
Low-grade inflammatory status, defined as:
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:
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
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
168 participants in 3 patient groups
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Central trial contact
Julie-Anne NAZARE; Karine CLEMENT
Data sourced from clinicaltrials.gov
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