Clinical trial NCT03860623: Effect of Oral Feeding on Gastric Emptying, Gut Blood Flow, and Hormone Responses in Obese and Healthy Weight Subjects
Official title: The Effect of Oral Feeding on Gastric Emptying, Small Bowel Water Content, Superior Mesenteric Artery Blood Flow, Plasma Hormone Concentrations and Blood Volume in Obese and Healthy Weight Subjects.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: satiety
gut blood flow
gastric emptying
obesity
incretin hormones
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2019-03-04
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Recruitment will be from the male population residing within 20 miles of the research site. This will include those from Nottinghamshire, Leicestershire and Derbyshire, UK

Brief summary: Obesity is a complicated condition that is poorly understood. The aim of this study is to increase our knowledge of how the condition may arise, and what makes obese people remain obese.

We will be investigating 12 people who are overweight and comparing them to 12 people who are lean, to look at how quickly food empties out of the stomach (gastric emptying) and travels through the gut, what the blood flow to the gut is, and also to examine the hormones which are involved in determining how full people feel after eating. In order to do this, we will be using a magnetic resonance imaging (MRI) scanner, and performing blood tests.

The rate of gastric emptying may have an impact on satiety (how full one feels) and has been implied in the development of obesity. This effect has been shown to impact on subsequent meal intake to a greater degree in overweight subjects, and may be due to a difference in gastric emptying of food in overweight individuals, or to hormones such as ghrelin, glucagon-like peptide 1, and Peptide YY.

Detailed description: The World Health Organisation (WHO) has deemed being overweight or obese as the fifth leading cause for global deaths, with more than 1.9 billion adults being defined as overweight, and 600 million defined as being obese. Conditions associated with obesity, such as stroke, type 2 diabetes, certain cancers, cardiovascular, fatty liver and airway disease can lead to premature death. Obesity results from an imbalance in energy intake versus expenditure, and fat mass accumulates. Studies have indicated that obese animals have a faster gastric emptying time, a weaker contraction of the duodenum, but a stronger contraction and relaxation of the ileum, with associated changes in gastrointestinal neurohormonal levels. The rate of gastric emptying may have an impact on feelings of satiety and has been implied in the pathogenesis of obesity. Moreover, mesenteric blood flow increases 3-fold following a meal and in a swine experimental model, a reduction in weight gain was seen when blood flow was intentionally limited to the gut using flow-restricting endovascular stenting. The authors concluded that this intervention may play a role in the treatment of obesity where other interventions have failed or are inappropriate; however the role of blood flow to the gut in obese individuals is important to elucidate. We hypothesize that nutrient absorption in obese and healthy weight individuals after a standardized meal is determined by differences in gastric emptying and mesenteric blood flow which give rise to different insulin, glucose and gut hormone responses. These may be contributory mechanisms to the evolution or maintenance of obesity.

The aim of this study is to establish the effects of food ingestion on gastric emptying, gallbladder emptying, small bowel water content and splanchnic blood flow as measured by serial magnetic resonance imaging (MRI) in the context of changes in plasma gastrointestinal hormone secretion in human subjects who are obese or healthy weight. In addition, this pilot study will provide the data necessary to power a larger study investigating methods of dietary manipulation in the treatment of obesity.

Method: In order to normalize the pre-study diet, volunteers will have consumed a standard diet for the 3 days immediately before the study visit, which will be based on foods in their normal diet and will be designed to meet their estimated energy requirements and provide 15% of total daily energy intake as protein, 35% as fat and 50% as carbohydrate. Participants will report at 0800 hours following a fast from midnight and after having abstained from alcohol, nicotine, and caffeine from 1800 hours the day before. On arrival, participants will be given a drink of water (200ml). A retrograde cannula will be inserted into a dorsal foot vein after prior intradermal infiltration of 1% lidocaine, with the foot placed in a magnetic resonance (MR) compatible warming box that we have developed, for arterialized-venous blood sampling. Prior to baseline blood sampling, participants will undergo a magnetic resonance imaging (MRI) scan to determine baseline values for superior mesenteric artery (SMA) blood flow, small bowel water content and gastric fluid and gas volumes. Liver fat, visceral fat and subcutaneous fat volumes will also be assessed at this time. Subsequently, a blood sample will be drawn for analysis of concentrations of hemoglobin, glucose, insulin, glucagon-like peptide 1 (GLP-1), glucagon-like peptide 2 (GLP-2), ghrelin and peptide YY (PYY). Serum osmolality will also be measured and subjective appetite assessed using visual analogue scales. The participants will then be given the test meal (in an upright, seated position) and asked to consume it within 15 minutes. The test meal will be comprised of pasta, cheese and tomato sauce, and provides 13% of total energy (E) from protein, 39%E fat, and 48%E carbohydrate.

Following the test meal (time = 0 minutes), subjective appetite will be measured as before, then participants will be scanned at 30 minute intervals for 4 hours to assess gastric emptying, gastric accommodation, gastric motility and small bowel water content, as well as SMA blood flow. Blood samples will be drawn at 15 minutes, then every half hour until 240 minutes after the test meal, with a final blood sample taken at 300 minutes. Subjective appetite will be assessed every hour over the 300 minute study.

Eligibility criteria: Inclusion Criteria:

* BMI 30-40 kg/m2
* BMI 18-25 kg/m2; those with BMI up to 28kg/m2 will be included if waist circumference is \<96cm.
* Males
* Aged 18-60yrs

Exclusion Criteria:

* Acute illness in the preceding 6 weeks
* Taking regular medication
* History of deep vein thrombosis or clotting disorders
* Hypertension
* Diabetes
* Any clinically significant findings at screening
* History of substance abuse
* Demonstrating factors precluding safe MRI
* History of gastrointestinal motility disorders (e.g. gastroesophageal reflux disease -irritable bowel syndrome, gastroparesis, sphincter of Oddi dysfunction, etc.)
* Previous thoracic or abdominal surgery.
* Those who report having ≤3 bowel movements/week or \>2/day.

Primary outcomes:
measure: Gastric emptying rate
timeFrame: 240 minutes after feeding
Secondary outcomes:
measure: Stomach volume in the fasted state
timeFrame: baseline
measure: Superior mesenteric artery (SMA) blood flow in the fasted state
timeFrame: baseline
measure: superior mesenteric artery (SMA) blood flow response to feeding
timeFrame: 240 minutes after feeding
measure: Fasting blood glucose concentration
timeFrame: before feeding
measure: Blood glucose response to feeding
timeFrame: 300 minutes after feeding
measure: Fasting insulin concentration
timeFrame: baseline
measure: serum insulin response to feeding
timeFrame: 300 minutes after feeding
measure: Fasting plasma GLP-1 concentration
timeFrame: baseline
measure: Plasma GLP-1 response to feeding
timeFrame: 300 minutes after feeding
measure: Fasting plasma GLP-2 concentration
timeFrame: baseline
measure: Plasma GLP-2 response to feeding
timeFrame: 300 minutes after feeding
measure: Fasting plasma Ghrelin
timeFrame: baseline
measure: Plasma Ghrelin response to feeding
timeFrame: 300 minutes after feeding
measure: Fasting plasma peptide YY (PYY)
timeFrame: baseline
measure: Plasma peptide YY (PYY) response to feeding
timeFrame: 300 minutes after feeding
measure: Subjective satiety in the fasted state
timeFrame: baseline
measure: Subjective satiety after eating
timeFrame: immediately after eating the standard meal
measure: Subjective satiety response to eating
timeFrame: 300 minutes after eating
measure: visceral adiposity
timeFrame: baseline
measure: subcutaneous adiposity
timeFrame: before feeding
measure: hepatic lipid content
timeFrame: baseline
measure: Attrition rate
timeFrame: 1 year
measure: Recruitment rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
state: Notts
Study officials:
affiliation: University of Nottingham
name: Dileep Lobo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Alyami J, Spiller RC, Marciani L. Magnetic resonance imaging to evaluate gastrointestinal function. Neurogastroenterol Motil. 2015 Dec;27(12):1687-92. doi: 10.1111/nmo.12726.
citation: Hoad CL, Parker H, Hudders N, Costigan C, Cox EF, Perkins AC, Blackshaw PE, Marciani L, Spiller RC, Fox MR, Gowland PA. Measurement of gastric meal and secretion volumes using magnetic resonance imaging. Phys Med Biol. 2015 Feb 7;60(3):1367-83. doi: 10.1088/0031-9155/60/3/1367. Epub 2015 Jan 16.
citation: Totman JJ, Marciani L, Foley S, Campbell E, Hoad CL, Macdonald IA, Spiller RC, Gowland PA. Characterization of the time course of the superior mesenteric, abdominal aorta, internal carotid and vertebral arteries blood flow response to the oral glucose challenge test using magnetic resonance imaging. Physiol Meas. 2009 Oct;30(10):1117-36. doi: 10.1088/0967-3334/30/10/011. Epub 2009 Sep 16.