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Trial record 5 of 7645 for:    inflammation

APOA2 Gene, Diet, Inflammation and Gut Health

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03322449
Recruitment Status : Active, not recruiting
First Posted : October 26, 2017
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
Jose Ordovas, Tufts University

Brief Summary:
Nutrients and chemicals in food are able to regulate expression of genetic elements. Gene-nutrient interaction in response to unhealthy diets can increase an individual's risk, shifting the individual from health toward the development of chronic disease. The apolipoprotein A2 (APOA2) gene may either put individuals at risk for or protect from obesity in the presence of certain fats in food. The main purpose of this four-week study is to examine diet induced gene-nutrient interaction, with a focus on gut health, gut microbiota and inflammation in individuals who have either the CC or the TT form within a specific variant of the APOA2 Gene. The (2) one-week study diets, one plant based and the other animal based are separated by a (1) week return to your regular habitual without probiotic or prebiotic food products.

Condition or disease Intervention/treatment Phase
Inflammation Other: Animal Diet Other: Plant Diet Not Applicable

Detailed Description:

The primary objectives of this application are 1. To use a diet intervention setting to rigorously evaluate the mechanisms responsible for the previously observed effects, focusing on gut microbiota and markers of gut health and inflammation and 2. To prove that targeted dietary intervention based on genes can provide additional, tailored benefit to genetically vulnerable individuals. The overall hypothesis proposes that significant cross-talk between the human host genome, the microbiome, and the diet, defines the observed inter-individual variation in metabolic and physiological responses. Accordingly, the investigators propose the following specific aims and hypotheses.

AIM 1: To catalog the response of the plasma metabolome to diets differing in saturated fat and prebiotics content (animal-based diet versus plant-based diet) in individuals from the USA carrying CC (n=20) and TT (n=20) genotypes at the common APOA2 -265T>C SNP using a crossover, randomized dietary intervention study.

Our primary hypothesis states: A significant and biologically relevant proportion of the individual variation in changes in the plasma metabolome in response to dietary saturated fat and prebiotic intake will be due to APOA2-265T>C genotypes. Specifically, subjects homozygous (CC) for the less common C allele will respond to decreases in total dietary saturated fat and increases in prebiotics (i.e., plant-based diet) with significantly greater improvement of metabolites related to gut health, inflammation and other cardiometabolic traits than subjects homozygous (TT) for the common T allele.

AIM 2: To characterize differential impacts of low SFA/high prebiotic (plant-based) diet vs. high SFA/low prebiotic (animal-based) diets on gut microbiota patterns between CC and TT persons at APOA2-265T>C.

Our primary hypothesis states: CC subjects have a preference for high-fat and -protein foods and therefore high levels of Bacteroidetes, Actinobacteria and similar species in the gut are expected. Moreover, reducing intake of saturated fat and increasing prebiotics will be more effective in inducing a healthier gut microflora profile in CC subjects than in those with the TT genotype, with opposite effects observed when the diet is switched to one high in saturated fat.

AIM 3: To integrate the metabolomic and gut microflora taxonomic information generated in AIM1 and AIM2 in order to elucidate the physiological mechanism(s) by which diet impinges on metabolic pathways through APOA2 genotypes.

Our primary hypothesis states: A diet low in saturated fat and high in prebiotics induces beneficial changes in gut microbiota, metabolic processes and inflammation, which are significantly more pronounced in CC than in TT subjects.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: randomized crossover dietary intervention
Masking: Single (Investigator)
Primary Purpose: Prevention
Official Title: APOA2 Gene, Diet, Inflammation and Gut Health
Actual Study Start Date : October 13, 2017
Actual Primary Completion Date : April 30, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Animal Diet
during this Arm, the participants will receive a diet enriched in animal products
Other: Animal Diet
during one week participants will receive food products enriched in animal products and with high content of fat and protein

Experimental: Plant Diet
during this Arm, the participants will receive a diet enriched in plant products
Other: Plant Diet
during one week participants will receive plant products enriched in fiber and complex carbohydrates




Primary Outcome Measures :
  1. tryptophan metabolism [ Time Frame: 1 week per intervention arm ]
    The response of plasma metabolites related to tryptophan metabolism to diets differing in saturated fat and prebiotics content (animal-based diet versus plant-based diet) will vary in individuals carrying CC (n=20) and TT (n=20) genotypes at the common APOA2 -265T>C single nucleotide polymorphism (SNP)


Secondary Outcome Measures :
  1. Satiety assessment using plasma levels of leptin [ Time Frame: 1 week per intervention arm ]
    Plasma leptin (ng/ml) will be measured in plasma during each one of the intervention phases. The response of leptin (ng/ml) to a saturated fat rich diet will be less on subjects with the CC genotype at the APOA2 locus as compared to TT subjects

  2. adipose tissue metabolism [ Time Frame: 1 week per intervention arm ]
    Plasma adiponectin (micrograms/ml) will be measured in plasma during each one of the intervention phases. The response of adiponectin to a saturated fat rich diet will be less on subjects with the CC genotype at the APOA2 locus as compared to TT subjects

  3. Plasma Lipoproteins [ Time Frame: 1 week per intervention arm ]
    Plasma lipoprotein concentrations in mg/dl (VLDL, LDL, HDL) and subclasses assessed by proton nuclear magnetic resonance (NMR) spectroscopy

  4. Gut microbiota diversity and composition [ Time Frame: 1 week per intervention arm ]
    A low saturated fat (SFA)/high prebiotic (plant-based) diet and a high SFA/low prebiotic (animal-based) diets have a differential effect on gut microbiota patterns according to the presence of the CC or TT genotypes at the APOA2-265T>C variant

  5. Plasma levels of Interleukin 6 to assess inflammatory status [ Time Frame: 1 week per intervention arm ]
    Plasma Levels of interleukin-6 (IL6) (pg/ml) will be measured during each of the dietary phases. IL6 will be higher in CC subjects at the APOA2 locus when consuming a high fat diet than when consuming a low fat diet. A low fat diet will not elicit increased IL6 levels in TT APOA2 subjects.

  6. Plasma levels of tumor necrosis factor alpha to assess regulation of immune cells [ Time Frame: 1 week per intervention arm ]
    Plasma Levels of tumor necrosis factor alpha (TNFA)(pg/ml) measured during each diet phase, will be significantly different depending on diet and APOA2 genotype. TNFA will be higher in CC subjects at the APOA2 locus when consuming a high fat diet than when consuming a low fat diet. A low fat diet will not elicit increased TNFA levels in TT APOA2 subjects.

  7. Plasma levels of C-reactive to assess regulation of inflammation [ Time Frame: 1 week per intervention arm ]
    Plasma Levels of C-reactive protein (CRP) (mg/L) measured during each diet phase will be significantly different depending on diet and APOA2 genotype. CRP will be higher in CC subjects at the APOA2 locus when consuming a high fat diet than when consuming a low fat diet. A low fat diet will not elicit increased CRP levels in TT APOA2 subjects.

  8. Plasma levels of Lipopolysaccharides to assess gut inflammation [ Time Frame: 1 week per intervention arm ]
    Plasma Levels of lipopolysaccharides (LPS) (ng/ml) will be significantly different depending on diet and APOA2 genotype. LPS will be higher in CC subjects at the APOA2 locus when consuming a high fat diet than when consuming a low fat diet. A low fat diet will not elicit increased LPS levels in TT APOA2 subjects.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women
  • 18 years or older
  • Women who are not pregnant
  • A BMI ranging between 27 and 34

Exclusion Criteria:

  • Unexplained elevation in serum transaminases (i.e. >1.5 times the upper limit of normal) or with evidence of active liver disease, including primary biliary cirrhosis or pre-existing gallbladder disease
  • Severe renal dysfunction (serum creatinine >2.0mg/dL)
  • Excessive alcohol consumption (>2 drinks/day)
  • Preexisting cardiovascular disease (CVD)
  • Stable exertional angina pectoris requiring sublingual nitroglycerin within the prior 3 months
  • Uncontrolled tyoe 2 diabetes (T2D) (fasting glucose >126 mg/dl) or other significant endocrine disease.
  • Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg).
  • History of pancreatitis within 1 yr. prior to screening.
  • Subjects on lipid lowering or diabetes medications.
  • Smoking
  • Pregnancy
  • Body mass index (BMI) below 27 or greater than 34 kg/m2
  • Participants will also be excluded for drug abuse, extreme dietary habits, multiple food allergies, extreme levels of physical or athletic activity, or by changes in body weight >20 lbs. during the last 6 months
  • Current use of antibiotics or during the previous 4 weeks.
  • Inability to follow any of the experimental diets (including being vegetarian) or to perform the sampling required for this study
  • Use of herbal supplements that may alter the gut microflora
  • Autoimmune diseases
  • Recent colonoscopy (within the previous two months)
  • Use of antidiarrheal medication
  • Thyroid diseases
  • Use of omega-3 supplements (unless it is discontinued one month prior to the beginning of the study).

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): NCT03322449


Locations
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United States, Massachusetts
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts University
Investigators
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Principal Investigator: Jose M Ordovas, PHD JM-USDA HNRCA at Tufts University
Publications:
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Responsible Party: Jose Ordovas, Senior Scientist, Tufts University
ClinicalTrials.gov Identifier: NCT03322449    
Other Study ID Numbers: 2016-08911
First Posted: October 26, 2017    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jose Ordovas, Tufts University:
APOA2
Inflammation
gene
diet
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes