Gut, Immune, and Vascular Health in Metabolically Healthy Obesity

Официальное название

Impaired Gut-Vascular Axis as a Unique Driver of Cardiovascular Disease in Metabolically Healthy Obesity

Обзор

The investigators seek to better understand how a single high-fat meal impacts gut, immune, and vascular outcomes in individuals with "metabolically healthy obesity" (obesity and largely normal cardiometabolic profile) and "metabolically healthy normal-weight individuals." Second, the investigators seek to understand how a prebiotic fiber (inulin) impacts gut, immune, and vascular outcomes in individuals with "metabolically healthy obesity."

Подробное описание

This study consists of two parts (part 1 and part 2) that are approved under the same IRB approval code. As a result, there is only one unique identifier for the entirety of this project. As a results, the investigators have included both parts in this registration.

Part 1 of project:

The investigators will recruit individuals with a BMI in the normal (18.5-24.9 kg/m2) or obesity (\>30.0 kg/m2) ranges from the Ball State University campus and surrounding communities. At a screening visit, the investigators will measure metabolic syndrome risk (blood pressure, triglycerides, glucose, HDL-C) to see if individuals meet criteria for "metabolically healthy obesity" and "metabolically healthy normal-weight" - our two groups of interest.

Each participant will complete one meal trial. At the meal trial, an intravenous catheter will be inserted and baseline blood sample collected. Next, vascular assessments (i.e., flow mediated dilation \[FMD\], pulse wave analysis \[PWA\], pulse wave velocity \[PWV\]) will be completed. Then, participants will consume the high-fat meal consisting of heavy cream, chocolate syrup, and protein powder. The meal will contain \~700 calories (55g fat).

Following completion of the meal, blood samples will also be collected at 1-, 2-, 3-, 4-, 5-, and 6-hours. At each time point the investigators will collect serum to assess biomarkers of intestinal permeability and inflammation. Serum will also be used in mechanistic experiments where the investigators will treat endothelial cells in culture with serum from participants pre/post high-fat meal and examine differences in gene and protein expression, as well as nitric oxide production. Additional blood will be collected for peripheral blood mononuclear cell isolation at baseline and 3 hours. Vascular assessments listed above will be repeated at 2-, 4-, and 6-hours.

Participants will provide a stool sample collected at home for microbiome analyses.

Part 2 of project:

The investigators will recruit individuals with a BMI in the obesity (\>30.0 kg/m2) range from the Ball State University campus and surrounding communities. At a screening visit, the investigators will measure metabolic syndrome risk (blood pressure, triglycerides, glucose, HDL-C) to see if individuals meet criteria for "metabolically healthy obesity" - our sole group of interest.

Qualifying participants will report for a baseline assessment. At the baseline assessment, the investigators will collect fasting blood samples to assess biomarkers related to gut, immune, and vascular health. Serum will also be used in mechanistic experiments where the investigators will treat endothelial cells in culture with serum from participants pre/post intervention and examine differences in gene and protein expression, as well as nitric oxide production. Next, vascular assessments (i.e., flow mediated dilation \[FMD\], pulse wave analysis \[PWA\], pulse wave velocity \[PWV\]) will be completed. This will conclude data collection and participants will be randomized to receive 6 weeks of supplemental inulin (a soluble fiber) or a placebo (maltodextrin). At 2-, 4-, and 6-weeks of the intervention, the same samples and measurements will be collected at in-lab visits. Stool samples will be collected at baseline and 6 weeks.

Вмешательства

• Пищевая добавка Inulin Supplementation
  Half of participants in part 2 will recieve supplemental inulin or placebo (maltodextrin).
• Пищевая добавка Maltodextrin (Placebo)
  Half of participants in part 2 will recieve supplemental inulin or placebo (maltodextrin).
• Другое High-fat meal
  All participants in part 1 (both metabolically healthy normal weight and metabolically healthy obesity) will consume a high-fat meal designed to invoke changes in gut, immune, and vascular parameters.

Первичные конечные точки

• Serum lipopolysaccharide binding protein [Срок оценки: Through study completion, up to 2 years]
• Serum interleukin-6 [Срок оценки: Through study completion, up to 2 years.]
• Flow-mediated dilation [Срок оценки: Through study completion, up to 2 years]
• Serum C reactive protein [Срок оценки: Through study completion, up to 2 years]
• Serum lipopolysaccharide [Срок оценки: Through study completion, up to 2 years]
• Serum TNF-alpha [Срок оценки: Through study completion, up to 2 years]
• Serum zonulin [Срок оценки: Through study completion, up to 2 years.]

Вторичные конечные точки (10)

• Augmentation Index [Срок оценки: Through study completion, up to 2 years]
• Pulse-wave velocity [Срок оценки: Through study completion, up to 2 years]
• Serum soluble CD14 [Срок оценки: Through study completion, up to 2 years]
• Serum IL-1 beta [Срок оценки: Through study completion, up to 2 years]
• Serum soluble VCAM-1 [Срок оценки: Through study completion, up to 2 years]
• Peripheral blood mononuclear cell transcriptome [Срок оценки: Through study completion, up to 2 years]
• Serum treated HAEC transcriptome [Срок оценки: Through study completion, up to 2 years]
• Serum treated HAEC eNOS and NFkB protein expression [Срок оценки: Through study completion, up to 2 years]
• Microbiome composition (shotgun sequencing) [Срок оценки: Through study completion, up to 2 years]
• Serum treated HAEC nitric oxide production [Срок оценки: Through study completion, up to two years.]

Критерии участия

Критерии включения

• 18-55 years old.
• BMI is 18.5-24.9 kg/m2 or >30kg/m2 (part 1). BMI > 30 kg/m2 (part 2)
• Not pregnant or expecting to become pregnant (females only).
• Not postmenopausal (females only).
• Have 0-1 risk factors based on blood pressure, blood sugar, triglycerides, and HDL-cholesterol ("good cholesterol").
• Have not been diagnosed with an advanced cardiometabolic condition (e.g., cardiovascular disease, type 2 diabetes).
• Have not been diagnosed with a chronic inflammatory or gastrointestinal condition (e.g., rheumatoid arthritis, inflammatory bowel disease).
• Do not regularly take anti-inflammatory drugs (more than 2x week) or are able to temporarily suspend use of anti-inflammatory drugs three days prior to the study visit.
• Have not taken antibiotics or probiotics in the last month.
• Do not use lipid-lowering drugs (e.g., statins), glucose-lowering drugs (e.g., metformin), or anti-hypertensive drugs.
• Do not use weight-loss drugs (e.g., Ozempic, Wegovy).
• Have not had any surgery that alters the stomach/gastrointestinal tract (e.g., gastric sleeve, gastric bypass).
• Do not use tobacco products or any illicit drugs.
• Do not have a pacemaker.
• Do not have dietary restrictions prohibiting consumption of the provided meal (e.g., vegan/vegetarian diets, gluten-free diet, relevant food allergies).
• Able to stay in the supine position in the dark for at least 10 minutes (related to vascular measurements)

Критерии исключения

• Not 18-55 years old.
• BMI is not 18.5-24.9 kg/m2 or >30kg/m2 (part 1). BMI is not > 30 kg/m2 (part 2)
• Pregnant or expecting to become pregnant (females only).
• Postmenopausal (females only).
• Do not have 0-1 risk factors based on blood pressure, blood sugar, triglycerides, and HDL-cholesterol ("good cholesterol").
• Have been diagnosed with an advanced cardiometabolic condition (e.g., cardiovascular disease, type 2 diabetes).
• Have been diagnosed with a chronic inflammatory or gastrointestinal condition (e.g., rheumatoid arthritis, inflammatory bowel disease).
• Regularly take anti-inflammatory drugs (more than 2x week) or are unable to temporarily suspend use of anti-inflammatory drugs three days prior to the study visit.
• Have taken antibiotics or probiotics in the last month.
• Use lipid-lowering drugs (e.g., statins), glucose-lowering drugs (e.g., metformin), or anti-hypertensive drugs.
• Use weight-loss drugs (e.g., Ozempic, Wegovy).
• Have had any surgery that alters the stomach/gastrointestinal tract (e.g., gastric sleeve, gastric bypass).
• Use tobacco products or any illicit drugs.
• Have a pacemaker.
• Have dietary restrictions prohibiting consumption of the provided meal (e.g., vegan/vegetarian diets, gluten-free diet, relevant food allergies).
• Not able to stay in the supine position in the dark for at least 10 minutes (related to vascular measurements)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Другое

Центры проведения

США · 1 центр

• Health Professions Building — Muncie

Идентификаторы

NCT: NCT07559227 · IRB-FY2026-239

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗