Clinical trial NCT04170010: Long Term Effects of Weight Loss on Post-prandial Gut Hormone Responses and Meal Induced Thermogenesis
Official title: Postprandial Gut Hormone Responses and Meal-induced Thermogenesis After Non-surgical Long-term Weight Loss; Comparison With Surgically Treated Obese Individuals
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Morbid Obesity
Keywords: Weight loss
Gut peptides
Meal-induced thermogenesis
Glycemia
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
First posted: 2019-11-20
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Intervention group: participants of NCT03851874 trial Control group: conservatively (non-surgically, non-pharmaceutically) managed obese individuals among ambulatory patients of the obesity outpatient clinic of the 1st Department of Propaedeutic Internal Medicine ("Laiko" General Hospital)

Brief summary: A study to examine post-prandial gut-hormone secretion, meal-induced thermogenesis, fasting plasma metabolomic/lipidomic and cardiovascular indices among surgically managed obese individuals in the long term compared to conservatively managed obese patients.

Detailed description: This is a protocol for the study of post-prandial gut peptide response and meal-induced thermogenesis in a group of 15 conservatively managed (through diet and exercise) morbidly obese individuals. During two separate visits in the study site, anthropometric and bioelectric impendence data will be collected, resting metabolic rate will be measured, and the patients will undergo a panel of cardiovascular examinations (heart rate variability, baroreflex sensitivity, heart ultrasound). On a separate occasion, they will consume a standardized test mixed meal and complete visual analog scales for the subjective assessment of hunger and fullness every 30 minutes for 3 hours. At the same time points, blood samples will be collected for the consequent measurement of glucose, insulin, lipids, and gastrointestinal hormones. Additionally, immediately before and at 60', 120', 180' after the start of the consumption of the test meal, the resting metabolic rate of each participant will be assessed through indirect calorimetry, to quantify meal-induced thermogenesis. The observed induction of satiety and suppression of hunger, post prandial gut-peptide mobilization and change in metabolic rate will be compared to those of participants of trial no NCT03851874 (Morbidly obese patients that have undergone either Roux en Y gastric bypass or sleeve gastrectomy and participated in trial NCT03851874). Participants in the aforementioned cohort have been already followed-up during the first postoperative year and will attend the study site for another follow-up visit approximately 10 years postoperatively, whereby the same diagnostic evaluation described above will take place. Data analysis will take place within the bariatric cohort (longitudinal analysis of the effects of surgery and surgery types on anthropometric parameters, fasting and postprandial glycemia and lipemia, fasting NMR-Metabolomic/Lipidomic profiles, Indices of insulin resistance, echocardiography, energy expenditure) as well as between the two groups in a cross-sectional manner.

Eligibility criteria: Inclusion Criteria:

* For the conservatively managed cohort:

  1. Morbid obesity based on BMI \> 40kg/m2, managed exclusively with conservative measures (hypocaloric diet and/or increased physical activity and/or behavioral therapy)
  2. Age between 18 and 65 years
* For the bariatric cohort: Participation in NCT03851874 trial

Exclusion Criteria:

1. Serious and life threatening comorbidities (renal, cardiac, liver failure, or malignancy)
2. Alcohol or other substance abuse
3. Use of licenced or off-label weight loss medications during the past 6 months
4. Concurrent psychiatric illness
5. Known history of diabetes mellitus (remitted cases excluded)

Primary outcomes:
measure: Change in postprandial Gut peptide (ghrelin, Gastric Inhibitory Peptide, Secretin, Peptide Tyrosine-Tyrosine - , Glucagon-like peptide - 1, Oxyntomodulin, Glicentin) responses
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in weight, fat mass and lean body mass
timeFrame: 8-10 years following primary weight-loss intervention
Secondary outcomes:
measure: Change in postprandial glycemia
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in postprandial insulinemia
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in postprandial triglyceridemia
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in Insulin resistance
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in serum metabolomic and lipidomic parameters
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in resting metabolic rate following meal ingestion
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in fasting serum adipokines
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in fasting plasma Activins and follistatins
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in postprandial Visual Analog Scale scores for hunger and satiety
timeFrame: 8-10 years following primary weight-loss intervention
Other outcomes:
measure: Change in baroreflex sensitivity
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in heart rate variability
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in aortic distensibility
timeFrame: 8-10 years following primary weight-loss intervention
measure: Change in echocardiographic cardiac phenotype
timeFrame: 8-10 years following primary weight-loss intervention
Locations:
city: Athens
country: Greece
facility: Diabetes Clinical Research Laboratory, 1st Department of Propaedeutic Internal Medicine
Study officials:
affiliation: First Department of Propaedeutic Medicine, NKUA
name: Alexandros Kokkinos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perakakis N, Kokkinos A, Peradze N, Tentolouris N, Ghaly W, Pilitsi E, Upadhyay J, Alexandrou A, Mantzoros CS. Circulating levels of gastrointestinal hormones in response to the most common types of bariatric surgery and predictive value for weight loss over one year: Evidence from two independent trials. Metabolism. 2019 Dec;101:153997. doi: 10.1016/j.metabol.2019.153997. Epub 2019 Oct 28.
citation: Liaskos C, Koliaki C, Alexiadou K, Argyrakopoulou G, Tentolouris N, Diamantis T, Alexandrou A, Katsilambros N, Kokkinos A. Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a Short-term Follow-up Analysis. Obes Surg. 2018 Dec;28(12):3997-4005. doi: 10.1007/s11695-018-3454-y.
citation: Yousseif A, Emmanuel J, Karra E, Millet Q, Elkalaawy M, Jenkinson AD, Hashemi M, Adamo M, Finer N, Fiennes AG, Withers DJ, Batterham RL. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans. Obes Surg. 2014 Feb;24(2):241-52. doi: 10.1007/s11695-013-1066-0.
citation: Stefanadis C, Stratos C, Boudoulas H, Kourouklis C, Toutouzas P. Distensibility of the ascending aorta: comparison of invasive and non-invasive techniques in healthy men and in men with coronary artery disease. Eur Heart J. 1990 Nov;11(11):990-6. doi: 10.1093/oxfordjournals.eurheartj.a059639.