Individual Factors Related to Chronic Low-grade Inflammation and Cardiometabolic Disease Risk

Healthy Clinical Trial

— PINEAPPL  

Official title:

Integrative and Personalized Lifestyle Approach to Reduce Low-Grade Inflammation in People at Risk of Cardiometabolic Diseases

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06355544
• Other study ID #: PINEAPPL2023
• Secondary ID: 2023-A02494-41
• Status: Not yet recruiting
• Start date: April 2024
• Est. completion date: June 30, 2026

Study information

• Verified date: April 2024
• Source: Integrative Phenomics
• Contact: Karine Clément, MD, PhD
• Phone: 33142177031
• Email: karine.clement[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to learn about low-grade inflammation in healthy individuals and individuals with overweight or obesity. The main questions it aims to answer are: - Whether it is possible to predict low-grade inflammation - What are the medical, biological, and lifestyle variables related to low-grade inflammation? Participants will be asked to: 1. Attend a general medical visit to collect vital signs, anthropometric measurements, and collect blood samples. 2. Complete questionnaires and collect a stool sample at home.

Description:

Cardiometabolic diseases (CMDs) are a heterogeneous spectrum of nutrition-related chronic diseases, ranging from obesity to diabetes and, ultimately, to acute and chronic cardiovascular diseases. Once established, these diseases are usually irreversible and evolve over time. Since these diseases are born out of societal and lifestyle changes, the cornerstones of prevention and management are changes in nutrition and lifestyle. This inevitable increase in CMDs, including obesity, particularly affects socially vulnerable populations. The etiology of cardiometabolic diseases is complex and involves environmental, biological and genetic elements. Weight gain is at the heart of these pathologies: it frequently precedes their development or contributes to the progression of these diseases. To this end, even modest weight loss is suggested as an important line of prevention or treatment of cardiometabolic diseases. For example, diabetes remission can be achieved with weight loss and is directly correlated with the amount of weight lost. Despite the beneficial effects of weight loss on preventing the progression of cardiometabolic diseases, maintaining weight loss is difficult, with only 30% of individuals achieving long-term weight loss (5 years). The same is true with the development of anti-obesity treatments (new analogues of glucagon-like peptide 1 (GLP1)); Discontinuation of treatment is accompanied by weight gain. In the case of diabetes, weight gain is associated with the recurrence of previously remitted diabetes. Chronic low-grade inflammation is tightly linked with obesity and a central feature of cardiometabolic diseases and associated diseases. Furthermore, it paves the way for future comorbidities. This inflammation is characterized by a rise of systemic or circulating inflammatory molecules. However, no single cytokine can reflect the inflammatory state seen in cardiometabolic diseases and these systemic factors are highly variable from subject to subject. Recently, combinatorial indexes, using multiple inflammatory markers have been strongly associated with coronary risks and Metabolic alterations. Over the past 10 years, the gut microbiome has become a recognized contributor to our metabolic health. Accumulating evidence has shown that the gut microbiome strongly reflects environmental and lifestyle changes (including nutrition) by altering its diversity and composition as well as its functions by producing molecules that interact with host organs, including the brain. The excess or deficit production of molecules produced by the microbiota, bacterial metabolites (such as trimethylamine oxide (TMAO), Imidazole propionate, branched-chain amino acids (BCAAs), or short-chain fatty acids (SCFAs), etc.) are molecules implicated in the link between the environment, microbiota and metabolic and inflammatory disturbances. Current strong evidence indicates that the gut microbiota is altered early in people with inflammatory diseases that include CMDs. Relationships between the inflammatory component of the diet and the gut microbiome have also been identified. In an effort to predict chronic-low grade inflammation in a real-world population and decipher the relationships between chronic low-grade inflammation and individual factors, comprising lifestyle, diet, behavior, environment, the gut microbiome, and health-related clinical data, the present study recruits a cohort of participants across age, sex, body mass index, and metabolic health spectra. Chronic low-grade inflammation markers of interest will be measured to establish a multi-component index of inflammation relative in the population.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 3000
• Est. completion date: June 30, 2026
• Est. primary completion date: May 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Male or female between the ages of 18 and 70 included,
• One of the following two criteria:
• Clinically at-risk group Body Mass Index between 25 (included) and up to 35 kg/m2 (excluded)
• Non-clinically at-risk group Body Mass Index between 18.5 (included) and up to 25 kg/m2 (excluded) and absence of metabolic syndrome criteria
• Subject covered by social security or a similar system.
• Ability to use a mobile phone application on a daily basis (food intake).
• Subject, after being informed of the contents of this study, fully understanding and accepting its purpose; and able to personally sign a written informed consent

Exclusion Criteria:

• Subject with diagnosed inflammatory disease or infection-related inflammation (viral

or bacterial) or medical history (viral) within the last 2 months:

• Rheumatoid arthritis, reactive or psoriatic arthritis (non-osteoarthritis)
• Inflammatory bowel disease (IBD) (Crohn's disease or ulcerative colitis) or irritable bowel syndrome
• Systemic lupus erythematosus
• Uncontrolled psoriasis
• Viral hepatitis or ongoing viral infection
• Seasonal virus (influenza-like illness)
• Subjects who have taken antibiotics in the last 2 months
• Subject under treatment within the last 2 months of an:
• Antiviral (for HIV, hepatitis, influenza, chickenpox/shingles)
• Oral, topical, or injectable treatment of a drug that modulates the inflammatory response (e.g. Corticosteroid, non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac, celecoxib, naproxen, aspirin, etc.)
• Dietary supplement that can modulate the inflammatory response (e.g.
• Omega 3 fatty acid, curcuma/turmeric, probiotic, prebiotics)
• Subject with diabetes (type 1 or 2) known treated prior to the inclusion visit (specifically subjects recently diagnosed or diagnosed with diabetes at the time of the laboratory assessment may be retained in the study if they are not taking anti-diabetic treatment): i.e. exclusion of subject with diabetes diagnosed with fasting blood glucose = 126 mg/dL (7.0 mmol measured twice/L OR glycated hemoglobin = 6.5% (48 mmol/mol) AND anti-diabetic therapy (metformin, GLP-1 receptor agonist, insulin, sulphonylurea, alpha-glucosidase inhibitor)
• Subject with severe or unstable hepatic, renal, cardiovascular, respiratory, endocrine, or metabolic disorders or cancer diagnosed with or without treatment
• Subject suffering from gastrointestinal disorders resulting in the use of laxatives or drugs for intestinal transit (e.g., loperamide) in the last 2 months.
• Subject with a complication or procedure in the last 2 months that could result in inflammation
• Minor or acute tendonitis, sprain, or contusion
• Severe contusion (e.g. Bone contusion)
• Major or invasive surgery
• Subject in a situation that, in the opinion of the investigator, could interfere with optimal participation in the present study or pose a particular risk to the subject.
• Subject currently participating in an interventional clinical study
• Subject not affiliated to the Social Security scheme
• Subject who did not comply with the exclusion period of the study in which they would have previously participated
• Subject not being able to use the internet

Related Conditions & MeSH terms

• Abdominal Obesity
• Healthy
• Hypercholesterolemia
• Hypertension
• Inflammation
• Low-grade Inflammation
• Metabolic Syndrome
• Metabolically Healthy Controls
• Normal Weight Adults
• Obesity
• Obesity, Abdominal
• Overweight
• Risk Factor, Cardiovascular

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Integrative Phenomics	Assistance Publique - Hôpitaux de Paris, Assistance Publique Hopitaux De Marseille, Centre Hospitalier Universitaire Dijon, Hopitaux Civils de Colmar, Institut Pasteur de Lille, University Hospital, Bordeaux

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Low-grade inflammation	Assessed as a z-score composed of six markers (C reactive protein (CRP), interleukin (IL)-6, serum amyloid-A (SAA), soluble intracellular adhesion molecule (sICAM), tumor necrosis factor alpha (TNF)-alpha) and categorized into 3 tertiles: Low/ Moderate/High	Baseline
Secondary	Gut microbiome metabolites	Consumption and production in mmol/day assessed through in silico metabolic modeling	Baseline
Secondary	Fasting glucose	Serum glucose in mg/dl	Baseline
Secondary	Stool microbiome composition	Relative abundance of microbiome taxonomies (Phyla, Order, Class, Family, Genus, Species), metagenomic species (MGS), and co-abundance genes (CAGs) in stool samples assessed through shot-gun sequencing	Baseline
Secondary	Stool microbiome functional pathways	Relative abundances of microbiome functional pathways assessed through metagenomics and in silico metabolic modeling	Baseline
Secondary	Systolic blood pressure	mmHg	Baseline
Secondary	Resting heart rate	Beats per minute	Baseline
Secondary	Serum glycated hemoglobin (HbA1c)	Percentage of HbA1c or mmol/L	Baseline
Secondary	Diastolic blood pressure	millimeters mercury (mmHg)	Baseline
Secondary	Height	Centimeters	Baseline
Secondary	Waist circumference	Centimeters	Baseline
Secondary	Neck circumference	Centimeters	Baseline
Secondary	Hip circumference	Centimeters	Baseline
Secondary	Body fat mass	Percentage of bodymass measured by impedance	Baseline
Secondary	Water body mass	Percentage of body mass measured by impedance	Baseline
Secondary	Lean body mass	Percentage of body mass measured by impedance	Baseline
Secondary	Serum fasting low-density lipoprotein	mmol/L	Baseline
Secondary	Fasting serum high-density lipoprotein	mmol/L	Baseline
Secondary	Fasting total serum cholesterol	mmol/L	Baseline
Secondary	Consumption of dietary macronutrients	Dietary macronutrient consumption assessed in g/day from dietary records and food frequency questionnaires	Baseline
Secondary	Consumption of dietary micronutrients	Daily micronutrient consumption (mg/d) assessed by dietary records and food frequency questionnaire	Baseline
Secondary	Consumption of dietary metabolites	Dietary metabolite consumption expressed in mmol/day assessed by dietary records and food frequency questionnaire	Baseline
Secondary	Food item consumption	Consumption of food items in g/day assessed by dietary records and food frequency questionnaires	Baseline
Secondary	Food group consumption	Consumption of food groups in g/day assessed by dietary records and food frequency questionnaires	Baseline
Secondary	Body weight	Kilograms	Baseline
Secondary	Serum Alanine Transaminase (ALT)	Serum Units per Liter (U/L)	Baseline
Secondary	Serum Aspartate Aminotransferase (ALT)	Serum Units per Liter (U/L)	Baseline
Secondary	Serum gamma-glutamyl transferase (GGT)	Serum Units per Liter (U/L)	Baseline
Secondary	Fasting serum triglycerides	mmol/L	Baseline
Secondary	Fasting serum uric acid	mmol/L	Baseline
Secondary	Fasting serum creatinine	mmol/L	Baseline
Secondary	Fasting serum insulin	mmol/L	Baseline
Secondary	Blood hemoglobin	grams per 100 milliliters (g/100ml)	Baseline
Secondary	Blood hematocrit	Percentage (%) of whole blood sample	Baseline
Secondary	Red blood cells	Cell counts in 10^9 per liter (10^9/L)	Baseline
Secondary	Red blood cell volume	Mean volume in cubic micrometers (um^3)	Baseline
Secondary	Hemoglobin relative red blood cell size	Mean relative hemoglobin relative to red blood cell size in percentage	Baseline
Secondary	Mean cell hemoglobin (MCH)	Mass of hemoglobin per red blood cell in picograms (pg)	Baseline
Secondary	Blood platelets	Cell counts expressed in billions/L (10^9/L)	Baseline
Secondary	White blood cells	Cell counts expressed in billions/L (10^9/L) and differential	Baseline
Secondary	Perceived quality of life	Self-perceived measurements of mental, physical, emotional, social, and general quality of life, fatigue, energy assessed by questionnaire	Baseline
Secondary	Eating behavior	Self-perceived emotional, uncontrolled, and eating restriction assessed by questionnaire	Baseline
Secondary	Physical activity	Total, leisure, work, and sports physical activity assessed by questionnaire	Baseline
Secondary	Stool consistency	Stool consistency assessed and self-reported by Bristol Stool Scale	Baseline
Secondary	Stress	Self-perceived stress assessed by questionnaire	Baseline
Secondary	Deprivation	Economic, material, and social deprivation assessed by questionnaire	Baseline
Secondary	Sleep	Sleep latency, duration, efficiency, quality, disturbances, and daytime dysfunction assessed by questionnaire	Baseline
Secondary	Sleep apnea	Binary value (yes/no) assessed from questionnaire	Baseline