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

NCT04130321 | Completed

• 1 other identifier: CAMU 2020-3350
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (20)

• Change in Endotoxemia

  Change between the beginning and the end of each treatment (12 weeks each)

• Change in Intestinal permeability

  Change between the beginning and the end of each treatment (12 weeks each)

• Change in Inflammation state of the tissue

  Change between the beginning and the end of each treatment (12 weeks each)

• Change in Short chain and branched chain fatty acids in the feces

  Change between the beginning and the end of each treatment (12 weeks each)

• Change in gut health

  Change between the beginning and the end of each treatment (12 weeks each)

Study Arms (2)

Camu camu

EXPERIMENTAL

Dietary Supplement: Camu camu

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Camu camu DIETARY_SUPPLEMENT

3 capsules of camu camu powder (500 mg / capsule) daily during 12 weeks

Camu camu

Placebo DIETARY_SUPPLEMENT

3 capsules of placebo daily during 12 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Laval University: lead

Study Sites (1)

INAF, Université Laval

Québec, G1V 0A6, Canada

Location

MeSH Terms

Conditions

Overweight; Congenital Microtia; Endotoxemia; Metabolic Syndrome; Insulin Resistance; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Ear Diseases; Otorhinolaryngologic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 17, 2019
• Study Start: October 31, 2020
• Primary Completion: April 21, 2022
• Study Completion: April 21, 2022
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

CA (1)