Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04130321
Recruitment Status : Recruiting
First Posted : October 17, 2019
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
André Marette, Laval University

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.


Condition or disease Intervention/treatment Phase
Overweight Microtia Endotoxemia Metabolic Syndrome Insulin Resistance Non-Alcoholic Fatty Liver Disease Dietary Supplement: Camu camu Dietary Supplement: Placebo Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans
Actual Study Start Date : October 31, 2020
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Camu camu Dietary Supplement: Camu camu
3 capsules of camu camu powder (500 mg / capsule) daily during 12 weeks

Placebo Comparator: Placebo Dietary Supplement: Placebo
3 capsules of placebo daily during 12 weeks




Primary Outcome Measures :
  1. Change in Gut Microbiota Composition and Diversity [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Global variation of the fecal microbiota

  2. Change in fat accumulation in the liver [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of fat accumulation by magnetic resonance imaging (MRI)


Secondary Outcome Measures :
  1. Change in Endotoxemia [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Plasma Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP)

  2. Change in Intestinal permeability [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Plasma zonulin

  3. Change in Inflammation state of the tissue [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Fecal calprotectin and chromogranin

  4. Change in Short chain and branched chain fatty acids in the feces [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Measure short chain fatty acids in the feces

  5. Change in gut health [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of gastrointestinal symptoms using a standardized questionnaire (the gastrointestinal symptom rating scale (GSRS))

  6. Change in stool consistency [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of stool consistency using a standardized questionnaire (Bristol stool chart)

  7. Change in Glucose homeostasis [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of plasma glucose using a 3-hour oral glucose tolerance test

  8. Change in Glucose homeostasis [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of insulin concentration using a 3-hour oral glucose tolerance test

  9. Change in Glucose homeostasis [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of c-peptide concentration using a 3-hour oral glucose tolerance test

  10. Change in Glucose homeostasis [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of glycated haemoglobin

  11. Change in Lipid profile [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of plasma triglycerides (TG), Total cholesterol, LDL, HDL, Apolipoprotein B and free fatty acids

  12. Change in anthropometric measurements [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of BMI (measured with weight change and height throughout the protocol)

  13. Change in anthropometric measurements [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of waist circumference

  14. Change in body composition [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of body composition by osteodensitometry

  15. Change in chronic inflammation [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of plasma high sensitive C-Reactive Protein (hs-CRP)

  16. Change in liver health [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of aspartate transaminase and alanine aminotransferase (AST and ALT)

  17. Change in gene expression levels [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Transcriptomic analyses to investigate underlying mechanisms of action

  18. Change in circulating levels of plasma metabolites [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of camu-camu derived metabolites, short chain fatty acids, branched chain fatty acids, bile acids, phenolic compounds

  19. Change in camu camu-derived metabolites present in stool [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of metabolome: camu-camu derived metabolites, short chain fatty acids, branched chain fatty acids, bile acids, phenolic compounds

  20. Change in blood pressure [ Time Frame: Change between the beginning and the end of each treatment (12 weeks each) ]
    Evaluation of systolic and diastolic blood pressure



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04130321


Locations
Layout table for location information
Canada
INAF, Université Laval Recruiting
Québec, Canada, G1V 0A6
Contact: Julie Marois, M.Sc.    1-418-656-2131 ext 405764    julie.marois@fsaa.ulaval.ca   
Sponsors and Collaborators
Laval University
Layout table for additonal information
Responsible Party: André Marette, Professor, Laval University
ClinicalTrials.gov Identifier: NCT04130321    
Other Study ID Numbers: CAMU 2020-3350
First Posted: October 17, 2019    Key Record Dates
Last Update Posted: February 18, 2021
Last Verified: February 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Endotoxemia
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Congenital Microtia
Metabolic Syndrome
Insulin Resistance
Overweight
Body Weight
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Digestive System Diseases
Bacteremia
Sepsis
Infection
Toxemia
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Ear Diseases
Otorhinolaryngologic Diseases
Congenital Abnormalities