Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans

Metabolic Syndrome Clinical Trial

Official title:

Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04130321
• Other study ID #: CAMU 2020-3350
• Status: Completed
• Phase: N/A
• Start date: October 31, 2020
• Est. completion date: April 21, 2022

Study information

• Verified date: October 2022
• Source: Laval University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Previous work of the investigators demonstrated the anti-obesity and anti-steatosis potential of the Amazonian fruit camu-camu (CC) in a mouse model of diet-induced obesity [1]. It was demonstrated that the prebiotic role of CC was directly linked to higher energy expenditure stimulated by the fruit since fecal transplantation from CC-treated mice to germ-free mice was sufficient to reproduce the effects. The full protection against hepatic steatosis observed in CC-treated mice is of particular importance since nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. Thirty percent of adults in developed countries have excess fat accumulation in the liver, and this figure can be as high as 80% in obese subjects. NAFLD is an umbrella term encompassing simple steatosis, as well as non-alcoholic steatohepatitis which can lead to cirrhosis and hepatocellular carcinoma in up to 20% of cases. Up to now, except for lifestyle changes, no effective drug treatment are available. Previous work has suggested that CC possesses anti-inflammatory properties and could acutely reduce blood pressure and glycemia after a single intake. While CC could represent a promising treatment for obesity and fatty liver, no studies have thoroughly tested this potential in humans. Therefore, a robust clinical proof of concept study is needed to provide convincing evidence for a microbiome-based therapeutic strategy to counteract obesity and its associated metabolic disorders. The mechanism of action of CC could involve bile acid (BA) metabolism. BA are produced in the liver and metabolized in the intestine by the gut microbiota. Conversely, they can modulate gut microbial composition. BA and particularly, primary BA, are powerful regulators of metabolism. Indeed, mice treated orally with the primary BA α, β muricholic (αMCA, βMCA) and cholic acids (CA) were protected from diet-induced obesity and hepatic lipid accumulation. Interestingly, the investigators reported that administration of CC to mice increased the levels of αMCA, βMCA and CA. Primary BA are predominantly secreted conjugated to amino acids and that deconjugation rely on the microbial enzymatic machinery of gut commensals. The increased presence of the deconjugated primary BA in CC-treated mice indicate that a cluster of microbes selected by CC influence the BA pool composition. These data therefore point to an Interplay between BA and gut microbiota mediating the health effects of CC. Polyphenols and in particular procyanidins and ellagitannins in CC can also be responsible for the modulation of BA that can impact on the gut microbiota. Indeed, it has been reported that ellagitannins containing food like walnuts modulate secondary BA in humans whereas procyanidins can interact with farnesoid X receptors and alter BA recirculation to reduce hypertriglyceridemia. These effects are likely mediated by the remodeling of the microbiota by the polyphenols. In accordance with the hypothesis that the ultimate effect of CC is directly linked to a modification of the microbiota, fecal transplantation from CC-treated mice to germ-free mice was sufficient to recapitulate the lower weight gain and the higher energy expenditure seen in donor mice.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: April 21, 2022
• Est. primary completion date: April 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• BMI between 25 and 40 kg/m2
• Fasting triglyceride > 1,35 mmol/L
• Understanding of spoken and written french
• Accept to follow study instructions

Exclusion Criteria:

• Smoking
• Medication affecting glucose metabolism, blood lipid levels or blood pressure
• Metabolic disorders requiring treatment
• Diabetic subjects presenting HbA1c >6.5% or fasting glycemia >7 mmol/L
• Consumption of fruit or polyphenol supplements in the last 3 months
• Allergy or intolerance for camu camu or for an ingredient of the placebo
• Alcohol consumption of > 2 drinks / day
• Weight change > 5% of body weight in the last 3 months
• Major surgical operation in the last 3 months or planned in the next months
• Pregnant or breastfeeding women or women planning pregnancy in the next months
• Antibiotics intake in the last 3 months
• Regular probiotics intake in the last 3 months
• Gastrointestinal malabsorption
• Cirrhosis
• Chronic kidney disease
• Concomitant participation in another clinical trial

Related Conditions & MeSH terms

• Endotoxemia
• Fatty Liver
• Insulin Resistance
• Liver Diseases
• Metabolic Syndrome
• Microtia
• Non-Alcoholic Fatty Liver Disease
• Overweight

Intervention

Dietary Supplement:
• Camu camu
3 capsules of camu camu powder (500 mg / capsule) daily during 12 weeks
• Placebo
3 capsules of placebo daily during 12 weeks

Locations

Country	Name	City	State
Canada	INAF, Université Laval	Québec

Sponsors (1)

Lead Sponsor	Collaborator
Laval University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Gut Microbiota Composition and Diversity	Global variation of the fecal microbiota	Change between the beginning and the end of each treatment (12 weeks each)
Primary	Change in fat accumulation in the liver	Evaluation of fat accumulation by magnetic resonance imaging (MRI)	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Endotoxemia	Plasma Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP)	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Intestinal permeability	Plasma zonulin	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Inflammation state of the tissue	Fecal calprotectin and chromogranin	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Short chain and branched chain fatty acids in the feces	Measure short chain fatty acids in the feces	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in gut health	Evaluation of gastrointestinal symptoms using a standardized questionnaire (the gastrointestinal symptom rating scale (GSRS))	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in stool consistency	Evaluation of stool consistency using a standardized questionnaire (Bristol stool chart)	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Glucose homeostasis	Evaluation of plasma glucose using a 3-hour oral glucose tolerance test	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Glucose homeostasis	Evaluation of insulin concentration using a 3-hour oral glucose tolerance test	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Glucose homeostasis	Evaluation of c-peptide concentration using a 3-hour oral glucose tolerance test	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Glucose homeostasis	Evaluation of glycated haemoglobin	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in Lipid profile	Evaluation of plasma triglycerides (TG), Total cholesterol, LDL, HDL, Apolipoprotein B and free fatty acids	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in anthropometric measurements	Evaluation of BMI (measured with weight change and height throughout the protocol)	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in anthropometric measurements	Evaluation of waist circumference	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in body composition	Evaluation of body composition by osteodensitometry	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in chronic inflammation	Evaluation of plasma high sensitive C-Reactive Protein (hs-CRP)	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in liver health	Evaluation of aspartate transaminase and alanine aminotransferase (AST and ALT)	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in gene expression levels	Transcriptomic analyses to investigate underlying mechanisms of action	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in circulating levels of plasma metabolites	Evaluation of camu-camu derived metabolites, short chain fatty acids, branched chain fatty acids, bile acids, phenolic compounds	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in camu camu-derived metabolites present in stool	Evaluation of metabolome: camu-camu derived metabolites, short chain fatty acids, branched chain fatty acids, bile acids, phenolic compounds	Change between the beginning and the end of each treatment (12 weeks each)
Secondary	Change in blood pressure	Evaluation of systolic and diastolic blood pressure	Change between the beginning and the end of each treatment (12 weeks each)