Assess the Effects of Replacing Foods High in Refined Carbohydrates With Avocado on Biomarkers of Inflammation.

Official title

Effects of Avocado Consumption on Inflammation and Insulin Sensitivity in Adults With Elevated High Sensitivity-C-reactive Protein (Hs-CRP): A Randomized, Controlled Crossover Trial

Overview

The objective of this trial is to assess the effects of replacing foods high in refined carbohydrates, particularly added sugars, with avocado (isocaloric substitution) on biomarkers of inflammation and insulin sensitivity in adults with elevated hs-CRP and central adiposity. Eligible participants will complete two 4-week interventions (1 avocado/d and control) separated by a 2-week washout phase. Participants will complete a total of 7 clinic visits including one screening visit (visit 1, -7 days), one baseline visit (visit 2, day 0), two visits during each 4-week diet condition (visit 3 \& 6 on day 21 and visits 4 \& 7 on day 28), and one visit at the conclusion of the washout phase/start of the second condition (visit 5, day 0).

Interventions

• Other Avocado
  Active foods will provide the equivalent of one medium to large avocado/day in foods such as muffins and pudding, where avocado replaces refined carbohydrate, especially added sugars
• Other Control
  Control foods will have similar energy contents to active foods, but energy from avocado will be replaced with refined carbohydrate, especially added sugars.

Primary outcome measures

• Composite measure of inflammatory biomarkers [Time frame: Change from baseline (day 0) to end of each condition (day 28)]

Secondary outcome measures (12)

• Homeostasis model assessments of insulin resistance (HOMA-IR) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Homeostasis model assessments of β-cell function (HOMA-B) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Matsuda index of insulin sensitivity [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Disposition index [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• high sensitivity C-reactive protein (hs-CRP) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Interleukin-6 (IL-6) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Interleukin-1 beta (IL-1β) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Interleukin-10 (IL-10) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Tumor Necrosis Factor-alpha (TNF-α) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Fibrinogen [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Soluble Intercellular Adhesion Molecule-1 (sICAM-1) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]
• Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) [Time frame: Change from baseline (day 0) to end of each condition (day 28)]

Eligibility criteria

Inclusion criteria

• Male or female 21 - 74 years of age, inclusive;
• Baseline hs-CRP ≥2 to <10 mg/L;
• Central adiposity (waist circumference ≥35 inches in women and ≥40 inches in men);
• Body mass index 25.0 to 39.9 kg/m2;
• Normally active and judged by the Investigator to be in generally good health, based on medical history and screening measurements;
• Willing to consume daily study foods during each diet condition;
• Willing to maintain his/her regular physical activity pattern throughout the study period;
• Willing to follow test day instructions (refrain from consumption of alcoholic beverages and participation in vigorous physical activity for 24 hours and tobacco and caffeine for 1 hour prior to each test visit);
• No plans to change smoking, vaping, or other nicotine use habits during the study period; and
• Premenopausal women that are not using hormonal contraceptives must have a history of regular menstrual cycles (21-35 days per cycle) for at least 3 months prior to visit 1;
• Understands the study procedures and signs forms documenting informed consent to participate in the study and authorization for release of relevant protected health information to the study Investigator and is willing to complete study procedures.

Exclusion criteria

• Calculated energy needs of <1800 kcal/d per the Mifflin-St. Jeor Equation, with an adjustment for energy expended in physical activity;
• Known metabolic disease (e.g., type 1 or type 2 diabetes, metabolic dysfunction-associated steatohepatitis, etc.);
• Laboratory test result(s) of clinical significance based on the judgment of the Principal Investigator or qualified designee, including fasting glucose ≥126 mg/dL;
• Positive urine test for illicit drugs at visit 1;
• Clinical atherosclerotic disease;
• History or presence of clinically significant gastrointestinal, endocrine, renal, hepatic, hematologic, immunologic, dermatologic, pulmonary, pancreatic, neurologic, psychiatric, inflammatory or biliary disorder that, in the opinion of the Investigator, could interfere with the interpretation of the study results;
• History of cancer in the prior 2 years, except for non- melanoma skin cancer or carcinoma in situ of the cervix;
• Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg) at screening;
• Unstable use (defined as initiation or change in dose) of anti-hypertensive medication within 4 weeks of visit 1;
• Unstable use (defined as initiation or change in dose) of thyroid hormone replacement medication within 12 weeks of visit 1;
• Use of beta-adrenergic blockers and/or high-dose (>25 mg/d) thiazide diuretics within 4 weeks of visit 1;
• Use of diabetes medications including glucagon-like peptide-1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, alpha-glucosidase inhibitors, biguanides and biguanide combinations, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides and sulfonylureas and combination sulfonylureas within 4 weeks of visit 1;
• Unstable use (defined as initiation or change in dose, agent, or regimen) of statins within 4 weeks of visit 1;
• Use of lipid-altering drugs other than statins including, but not limited to bile acid sequestrants, cholesterol absorption inhibitors, or fibrates within 4 weeks of visit 1;
• Use of any prescription medication with known effects on inflammation (e.g., colchicine, systemic corticosteroids) within 4 weeks of visit 1;
• Frequent use (≥4 doses/week) of non-steroidal anti-inflammatory drugs (NSAID) within 2 weeks of visit 2;
• Use of weight-loss drugs (including over-the-counter medications and/or supplements) or participation in a structured weight loss program within 4 weeks prior to visit 1;
• Unstable use (initiation or change in dose) within 4 weeks of visit 1 of sex hormones. Multiphasic hormonal contraceptives in which the amount of sex hormone in the active pill varies by week (i.e., biphasic, triphasic, quadriphasic) are considered unstable doses of sex hormones and are exclusionary;
• History of bariatric surgery or plans to have any surgery during the study;
• History of any major trauma or major surgical event within 2 months of visit 1;
• Use of herbs or dietary supplements that may affect lipid metabolism, including but not limited to omega-3 fatty acid supplements with >500 mg of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), niacin (or its analogs) at doses >200 mg/d, sterol/stanol products, dietary fiber supplements, red rice yeast supplements, garlic supplements, and soy isoflavone supplements within 2 weeks of visit 2;
• Use of herbs and dietary supplements that may affect carbohydrate metabolism, including chromium picolinate, ginseng, cinnamon (as a supplement) and starch blockers within 2 weeks of visit 2;
• Recent weight change of ±4.5 kg (\~10 lbs.) within 3 months prior to visit 1;
• Has signs and symptoms of an active infection of clinical significance or has taken antibiotics within 5 days prior to any visit (washout is permitted by re-scheduling of the clinic visit);
• Extreme dietary habits (e.g., vegan, very low carbohydrate);
• History of an eating disorder (e.g., anorexia, bulimia nervosa, or binge eating) either diagnosed by a health professional or self-reported;
• Female who is pregnant, planning to be pregnant during the study period, lactating, or is of childbearing potential and is unwilling to commit to the use of a medically approved form of contraception throughout the study period;
• Known allergy, sensitivity, or intolerance to any components of the study foods;
• Exposed to any non-registered drug product within 4 weeks of visit 1;
• Currently participating in another research study;
• Use of hemp/marijuana products within 12 months of visit 1. Occasional use (e.g., once or twice a month) within 12 months of visit 1 is allowed but requires at least a 14-day washout prior to visit 2 and the participant must be willing to refrain from use during the study;
• Current or recent history (past 12 months of screening) or strong potential for illicit drug or alcohol abuse. Alcohol abuse will be defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz hard liquor); and
• Condition the Investigator believes would interfere with his or her ability to provide informed consent or comply with the study protocol, or which might confound the interpretation of the study results or put the person at undue risk.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Other

Study locations

United States · 2 centers

• Illinois Institute of Technology — Chicago
• University of Nevada, Las Vegas — Las Vegas

Identifiers

NCT: NCT07566325 · MB-2544

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗