Investigation of Acute Physiological Effects of Aspiration Therapy

In the present study, the investigators aim to investigate postprandial physiology in patients who have had the Aspire Assist® inserted. This will involve a standardised mixed meal test (MMT) with subsequent aspiration of gastric content compared to MMT without aspiration. Furthermore, a comparison will be made between the aspiration group and a control group in order to evaluate whether continuous treatment with aspiration therapy affect the postprandial physiology. The primary outcomes of the trial are differences in postprandial plasma/serum glucose, insulin and gut hormone excursions during MMT with and without aspiration. Secondary outcomes encompass evaluation of satiety, gastric emptying and gallbladder motility following MMT with and without aspiration. Also, food intake during a subsequent ad libitum meal will be evaluated.

Study Overview

• Status: Completed
• Conditions: Obesity; Weight Loss
• Intervention / Treatment: Other: Meal test

Detailed Description

It is generally agreed that the increasing incidence of obesity mainly is caused by the adoption of a sedentary lifestyle combined with excessive caloric intake. So far, preventive measures and interventions based on lifestyle modifications have not been able to affect the western lifestyle to a degree that remedies the increasing prevalence of obesity. Likewise, no medical interventions have yet been able to induce and maintain significant major weight loss in obese populations. In contrast, bariatric surgery prompts a significant and often sustained weight loss, which frequently triggers remission of obesity-related comorbidities. However, bariatric surgery is invasive, irreversible and costly. Aspiration therapy was introduced as a less invasive and cheaper treatment for obesity. According to some studies, aspiration therapy is nearly as effective as Roux-en-Y gastric bypass in terms of excess weight loss after one year. Thus, aspiration therapy may aspire as an alternative treatment option for obesity with lower risk of complications than bariatric surgery.

The risk of developing impaired glucose tolerance and overt type 2 diabetes rises along with increasing obesity. The estimated risk of developing type 2 diabetes increases 3-fold with a body mass index (BMI) of 25-29.9 kg/m2 (overweight) and ~20-fold with a BMI >35 kg/m2 (severely obese) compared to a normal BMI (<25 kg/m2) (6). Type 2 diabetes is a complex, multi-organ metabolic disorder and is associated with serious complications, reduced quality of life and early death. The disease is characterized by hyperglycaemia and, thus, elevated haemoglobinA1c (HbA1c) (>6.5% or >48mmol/mol), which is a blood parameter used clinically as a measure of mean blood glucose over time (~3 months). Studies have shown that up to 70% of the mean plasma glucose levels is caused by postprandial plasma glucose excursions. Moreover, postprandial hyperglycaemia in itself seems to be associated with an elevated risk of cardiovascular disease due to unfavourable effect on both small and large blood vessels. Accordingly, postprandial hyperglycaemia has been suggested to constitute a better predictor of mortality risk than fasting plasma glucose concentrations in both patients with type 2 diabetes and individuals with normal glucose tolerance. Since the prevalence of impaired glucose tolerance is ~2-fold higher in obese compared to lean individuals, postprandial hyperglycaemia poses a great risk of developing severe comorbidities such as cardiovascular disease and type 2 diabetes for obese individuals and may increase mortality in this group. It is yet unknown whether aspiration therapy can attenuate the plasma glucose response to a meal. Due to the reduced amount of food reaching the intestine after aspiration, it seems likely that aspiration therapy reduces postprandial plasma glucose excursions and thereby prevents potential postprandial hyperglycaemia.

It is well known that an orally administered glucose load elicits a greater insulin secretion response compared to an intravenous infusion of glucose resulting in identical plasma glucose elevations. This phenomenon is called the incretin effect. The incretin effect is primarily driven by the insulinotropic gut hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These so-called incretin hormones play crucial roles in regulation of glucose homeostasis and appetite. GLP-1 is produced in the intestinal mucosa by the so-called enteroendocrine L cells, which are predominantly localised in the distal part of the small intestine and the colon. GIP originates from enteroendocrine K 5 cells in the gut mucosa. K cells are assumed to be predominant in the proximal part of the small intestine. Both GLP-1 and GIP are secreted in response to ingestion of nutrients and have strong glucose-dependent insulinotropic effects on pancreatic beta cells. The incretin hormones are of interest in the present study, because impaired incretin effect is an early sign of dysmetabolism in obese individuals and a distinctive feature of type 2 diabetes, suggesting that the impaired glucose tolerance of these patients is, at least in part, due to a defective incretin system. Whether aspiration of gastric content after a meal affects postprandial incretin hormone response has not been elucidated. The investigators plan to investigate meal-induced incretin hormone excursions in plasma with and without aspiration therapy and compare the results to a matched control group.

In addition to GLP-1 and GIP, several other gut-related hormones are known to regulate glucose homeostasis and appetite. Glucagon is a peptide hormone secreted from the pancreatic alpha cells. Glucagon acts opposite to insulin by promoting hepatic gluconeogenesis and glycogenolysis causing increased plasma glucose concentrations. Oxyntomodulin and pancreatic peptide YY3-36 (PYY) are peptide hormones secreted by the enteroendocrine L cells in response to feeding and both suppress appetite. Gastrin is a hormone secreted by G cells localised in the pyloric antrum, duodenum and pancreas. Gastrin stimulates acid (HCl) secretion and gastric emptying by increasing gastric motility. Cholecystokinin (CCK) is a peptide hormone secreted by the enteroendocrine I cells in the duodenum. CCK promotes bile release from the gallbladder and also acts as an appetite suppressant. To this point, it is unknown how aspiration therapy affects these appetite- and glucose-regulating hormones during a meal. The investigators aim to investigate this during standardised mixed meal tests with and without aspiration.

Furthermore, it is relevant to examine the effect of aspiration therapy on satiety. Thus, the investigators aim to evaluate the effect of aspiration therapy on satiety before, during and after a mixed meal as well as food intake after the MMT with and without aspiration evaluated through an ad libitum meal provided at the end of the experimental days.

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for diabetes research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

It is planned to recruit up to 25 patients who have had the Aspire Assist inserted. Furthermore, 10 healthy control participants matched for age, weight, height, BMI and sex will be recruited

Description

Inclusion Criteria:

• Patient who have had the Aspire Assist inserted (the aspiration therapy group)
• Age between 18-75 years
• Able to understand written patient information and sign informed consent

Exclusion Criteria:

• Diagnosis of type 1 diabetes
• Severe comorbidities that, at the discretion of the investigators, exclude study participation (e.g. chronic obstructive pulmonary disease (COPD) stage III, significant cardiac arrhythmias etc.)
• Previous gastrointestinal surgery (excluding cholecystectomy and appendectomy)
• Gastrointestinal conditions making the participant unsuitable for participation (e.g. ulcerative colitis, Crohn´s disease, clinically significant food allergies, candidiasis etc.)
• Anaemia with a haemoglobin value <6.2 mmol/l (<10 g/dl) for women and <7.4 mmol/l (< 12 g/dl) for men at time of screening
• Abuse of alcohol and/or drugs, or any other co-existing conditions that will make the participant unsuitable to attend to the study schedule, as deemed by the investigators
• Pregnancy or desire to become pregnant during the study period
• Exceptional conditions which, at the discretion of the investigators, preclude the participation in the study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Obese patients treated with AspireAssist; Healthy, obese with BMI > 27, treated with AspireAssist for weight management, the postprandial glucose metabolism will be tested with a meal test	Other: Meal test; 240 min mixed meal test with aspiration using AspireAssist.
Matched controls; Healthy, obese with BMI > 27, the postprandial glucose metabolism will be tested with a meal test	Other: Meal test; 240 min mixed meal test with aspiration using AspireAssist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma glucose concentration	mmol/l, collected during mixed meal test and analysed by YSI STAT 2300	0-240 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Insulin	pmol/l, Collected during mixed meal test	0-240 min
plasma GLP-1	pmol/l, Collected during mixed meal test	0-240 min
Indirect Calorimetry	Resting metabolic rate measured by O2 consumption during mixed meal test	0-240 min
Gallbladder volume	Measured during mixed meal test by UL and calculated by this equation: π/6*D1*D2*D3/1000, D1 = longitudinal diameter, D2 = cross section width, D3 = cross sectional width	0-240 min
Ad libitum meal intake	post meal test	30 min
Appetite	Evaluated by visual analogue scale (VAS 0-10, where 0 is no appetite and 10 is very hungry) during mixed meal test	0-240 min
Plasma GLP-2	pmol/l, Collected during mixed meal test	0-240 min
Plasma GIP	pmol/l, Collected during mixed meal test	0-240 min
Plasma Glucagon	pmol/l, Collected during mixed meal test	0-240 min
Plasma PYY	pmol/l, Collected during mixed meal test	0-240 min
Plasma Oxyntomodulin	pmol/l, Collected during mixed meal test	0-240 min
plasma ghrelin	pmol/l, Collected during mixed meal test	0-240 min
Plasma acetaminophen	mmol/L, Collected during mixed meal test	0-240 min
plasma c-peptide	pmol/l, Collected during mixed meal test	0-240 min
Plasma CCK	pmol/l, Collected during mixed meal test	0-240 min
plasma gastrin	pmol/l, Collected during mixed meal test	0-240 min

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Filip K Knop, MD, Proff, Center for Diabetes Research, Gentofte Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss
• Other Study ID Numbers: H-16038453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes