The Effect of the Consumption of 4 Botanical Extracts on Immunity in Healthy Adults (B-4-Immune)

Study Overview
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Brief Summary
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This study will evaluate the capacity of botanical extracts to modulate immune mechanisms compared to a placebo group in healthy volunteers.

Detailed Description
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In this ex-vivo pilot study, healthy volunteers will consume extracts during 28 days and blood will be sampled at baseline and end of study. The purpose of this study is to evaluate the ex vivo immune responses with and without stimulation after consumption of botanical extracts and identify the main mechanisms involved. The effect of the consumption of 4 botanical extracts on the quality of life in healthy adults compared to placebo will be also analyzed.

Official Title
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The Effect of the Consumption of 4 Botanical Extracts (Acerola, Panax Ginseng, Echinacea, Quillaja) on the Innate and Adaptive Immune Response in Healthy Adults: a Pilot Randomized Placebo-controlled Clinical Trial

Conditions
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Healthy Subject, Immunity

Intervention / Treatment
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* Dietary Supplement: Botanical extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 40 and 60 years (limits included) 18,5 < Body Mass Index < 30 kg/m2 Without modification of their normal eating/drinking habits, body weight and physical activity patterns in the last 4 weeks Consumption of citrus fruits and fruit juices limited to two servings per day maximum in the last 7 days Consumption of caffeine < 400 mg/day in the last 2 weeks For non-menopausal women: with the same reliable contraception (oral or local hormonal contraception, surgery (ligation, bilateral ovariectomy), copper intrauterine device) since at least 3 cycles before the beginning of the study and agreeing to keep it during the entire duration of the study For menopausal women: without hormone replacement therapy Daily consumption of alcohol less than 2 glasses Non-smoking or tobacco consumption stopped for at least 12 months Good general and mental health according to the opinion of the investigator: no clinically significant and relevant abnormalities of medical history or physical examination Able and willing to participate to the study by complying with the protocol procedures as evidenced by his dated and signed informed consent form Affiliated with a social security scheme Accepts to be registered to the VRB site (Volunteers in Biomedical Research database) After V0 biological analysis the subjects will be eligible to the study on the following criteria: Normal values of complete blood count (CBC), hemoglobin, hematocrit, MVC (mean corpuscular volume), MCH (mean corpuscular haemoglobin), HCT (haematocrit), MCHC mean corpuscular haemoglobin concentration), RDW (Red cells Distribution width), MPV (mean platelet volume), PCT (plateletcrit), ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase), urea, creatinine, HDL-cholesterol, LDL-cholesterol, total cholesterol, TG (triglycerides), glycemia according to the investigators' opinion Negative pregnancy test: blood beta HCG < 5 IU/L for women in childbearing age Exclusion Criteria: Any vaccination 6 weeks before inclusion visit and/or any vaccination during the study Specific food diet/habits: high protein or vegan diet Subjects who exercise more than 150 min per weeks of intense activity (which ask for an important physical effort and need to breathe much more than usual; for example, lift heavy load, mountain biking, playing football..) and more than 5 hours per week of moderate activity (which ask for a moderate physical effort and need to breathe a little bit more than usual; for example lift moderate load, quiet biking… ) With a past or current allergic rhinitis (sneezing, eye and nose scratching) and/or asthma (cough, wheezing, shortness of breath) With a current or past disorder of neuropathy / diabetic neuropathy Suffering from a metabolic or endocrine disorder SBP > 139 and/or DBP > 89 mmHg Treated or untreated diabetes and/or any pancreatic disease With a current or past cardiac disease With a current or past liver disease (cirrhosis, fibrosis, NASH…) With a current or past pulmonary disease With a current or past renal disease With a significant risk of bladder/kidney stones Infectious disease in the last 6 weeks Untreated hypo/hyperthyroidism, or uncontrolled hypo/hyperthyroidism or treated hypo/hyperthyroidism for less than 3 months (treated hypo/hyperthyroidism stabilized for at least 3 months is accepted) Untreated hypertension, or uncontrolled hypertension, or treated hypertension for less than 3 months (treated hypertension stabilized for at least 3 months is accepted) Untreated hypercholesterolemia or uncontrolled hypercholesterolemia or treated hypercholesterolemia for less than 3 months according to the investigator's opinion (treated and controlled hypercholesterolemia stabilized for at least 3 months is accepted according to the investigator's opinion) Past or current inflammatory disease with an impact on immune responses (rheumatoid arthritis, bone metabolic disease, psoriasis, gout, symptomatic chondrocalcinosis and active infection…) Immunodeficient volunteer and/or current immunosuppressive therapy With a current or past auto-immune disease or immunodeficiency Gastrointestinal disease, gastroenteritis (within 4 weeks), intestinal occlusion, prolonged severe diarrhea, severe regurgitation, difficulty for swallowing Current cancer or in remission < 5 years and/or any past or current hematological cancers (exception: basal cell carcinoma, or non-squamous cell skin cancer, prostate cancer, or in situ carcinoma without any significative progression in the past 2 years) Antibiotics consumption in the past 3 months Chronic antiviral and/or antibacterial treatment Current heparin treatment or anti-coagulation drug Consumption of laxative in the past 3 months Subjects who take, nasal steroids, decongestants, antihistamines, combination cold formulas, anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs, ibuprofen, cyclo-oxygenase 2 inhibitors) and therapy with immunostimulants (cytokines, thymus fractions) in the last 4 weeks Consumption of any food supplement (including but not limited to omega-3-fatty acid, probiotic supplements, vitamin, mineral supplement, herbal immunostimulant, etc…) in the last 4 weeks Bariatric surgery or any disease that could lead to intestinal malabsorption of the study products With a known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient Pregnant and/or breastfeeding women or intending to become pregnant in the next 3 months Having a lifestyle deemed incompatible with the study according to the investigator including high level physical activity With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator Currently participating to another clinical trial or volunteer who has ended his participation to a previous clinical study in the past 90 days Having received, during the last 12 months, indemnities for clinical trial higher or equal to 4500 Euros Under legal protection (guardianship, wardship) or deprived from his rights following administrative or judicial decision Presenting a psychological or linguistic incapability to sign the informed consent Impossible to contact in case of emergency

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acerola<br>dietary supplement : acerola extract self administrated by mouth for 28 days 1 capsule per day | Dietary Supplement: Botanical extract<br>* 1 capsule per day<br>|
| Experimental: Panax ginseng extract<br>dietary supplement : panax ginseng extract self administrated by mouth for 28 days 1 capsule per day | Dietary Supplement: Botanical extract<br>* 1 capsule per day<br>|
| Experimental: Echinacea extract<br>dietary supplement : echinacea extract self administrated by mouth for 28 days 1 capsule per day | Dietary Supplement: Botanical extract<br>* 1 capsule per day<br>|
| Experimental: Quillaja extract<br>dietary supplement : quillaja extract self administrated by mouth for 28 days 1 capsule per day | Dietary Supplement: Botanical extract<br>* 1 capsule per day<br>|
| Placebo Comparator: Maltodextrin<br>dietary supplement : maltodextrin supplement self administrated by mouth for 28 days 1 capsule per day | Dietary Supplement: Botanical extract<br>* 1 capsule per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex vivo Immune blood cell response after challenges at baseline (before supplementation) and after 28 days of each botanical consumption compared to placebo | Innate immunity like response and adaptative cell activation | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Frequency of innate and adaptative immune cell before and after 28 days of consumption of each botanical extract compared to placebo | The variation between both visits of the frequency of several circulating cells from innate and adaptative immunity expressed in % of white blood cells and absolute values | 28 days | 
| 2. Variation of quality of life before and after 28 days of consumption of each botanical extract compared to placebo | Assessed by the SF-12-v2 (Short-Form Health Survey version 2) questionnaire. it is a generic patient-reported measure of health status that provides summary scores of physical and mental health. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning. | 28 days |