Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05268627 |
| Other study ID # |
R.21.10.1495 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 27, 2022 |
| Est. completion date |
January 27, 2023 |
Study information
| Verified date |
February 2022 |
| Source |
Mansoura University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: Obesity is an important public health concern. Surgery is effective but invasive
and expensive, and some obese persons are not good surgical candidates.
Aim:
Compare safety, feasibility and efficacy of endoscopic ultrasound guided boutlinum toxin
injection and GLP-1 agonists in treatment of obesity.
Methods Full written informed consent will be obtained from all patients.Patient
demographics.Detailed medical history.Complete clinical examination.The two methods of
intervention will be combined with prescription of several life style modifications as a 2000
kcal diet in men, or 1800kcal in women and moderate daily aerobic exercise (at least 30
minutes, 5 times a week) during 4 months and body weight will be assessed during a 16-week
follow-up period.BTA group:Esophagogastroduodenoscopy (EGD) will be done to all subjects
under conscious sedation. If no ulceration or retained food, EUS and BTA injection will be
performed under the same sedation. EUS examinations will be performed. BTA injections will be
made via a 25-gauge EUS needle. A ring of five injections will be made into the gastric
antral muscularis propria, 2 to 3 cm proximal to the pylorus. The subjects will receive 20 U
at each injection. Subjects will be assessed for complications after recovery from conscious
sedation and, again, by telephone the next day.During a 16-week follow-up period after BTA
injections, subjects will be weighed weekly.GLP1 group:GLP-1 receptor agonist (Liraglutide
subcutaneous once daily).We will start by 0.6 mg daily and we will raise the dose up to 3 mg
gradually if patient tolerated.During a 16 week follow up period, subjects will be weighed
weekly.
Description:
Introduction
Obesity is an important public health concern. Although most pharmacologic therapies have
targeted the central nervous system, surgical treatments induce satiation by decreasing the
size of the gastric reservoir and inducing maldigestion or malabsorption.
Surgery is effective but invasive and expensive, and some obese persons are not good surgical
candidates. Promising pharmacologic and endoscopic approaches to obesity include treatments
that affect gastric volume, gastric emptying, gastric compliance, and satiation.
In rats, botulinum toxin A (BTA) injected subserosally into the antrum resulted insignificant
decreases in caloric intake and body weight when compared to control and injected rats.
Subsequent open-label human studies and three small randomized trials have reported
conflicting results, with some studies finding little or no body weight loss after gastric
BTA injection and one randomized controlled trial showing statistically significant decreases
in gastric emptying and body weight . These trials differed in BTA dose (100 to 300 U in
Botox formulation equivalents) and location of injections (antrum alone vs. antrum, body, and
cardia). Depth of injection in the gastric wall was largely unknown in these studies, as
endoscopic ultrasound (EUS) was not used to guide injection into the muscularis propria or
subserosal layers.
In a study by Topazian. (2008), mean body weight reduction was similar in subjects receiving
100 or 300 U BTA (5.0 vs. 4.8 kg). There was a no significant trend toward loss of more body
weight in the three subjects who developed decreased gastric emptying after receiving 300 U
BTA. Also EUS guidance would help to assure injection of BTA in the gastric muscularis
propria and subserosal layers of the gastric wall.
Glucagon-like peptide 1 (GLP-1) is a cleavage product of the pre- proglucagon gene which is
expressed in the α-cells of the pancreas, the L-cells of the intestine, and neurons located
in the caudal brainstem and hypothalamus. GLP-1 is primarily synthesized and secreted by the
L cells of the distal small intestine in response to a nutrient load, although non-nutrient
driven secretion has also been reported. GLP-1 is also synthesized by a small population of
neurones in the nucleus of the solitary tract (NTS) in the caudal brainstem which project to
areas in the hypothalamus and hindbrain that express GLP-1 receptors (GLP-1- R).
In response to a meal, GLP-1 delays gastric emptying and increases gastric volumes. GLP-1
enhances insulin secretion and inhibits glucagon-release in a glucose-dependent manner both
in normal individuals as well as in patients with type 2 diabetes. In patients with type 2
diabetes, GLP-1 agonist infusion in pharmacologic doses enhanced satiation and promoted
weight loss. Hence GLP-1 therapy in humans reduces food intake, appetite and hunger and
promotes fullness and satiety with the ultimate result of promoting weight loss.
The weight loss observed with GLP-1 agonist therapy may be associated with reductions in
total body fat, in particular visceral and truncal adipose.
Also of interest is the successful use of GLP-1 agonists in the treatment of hypothalamic
obesity, suggesting that at least in this cohort, GLP-1 analogues were capable of inducing
weight loss despite hypothalamic damage.
Unlike pure dietary measures, weight loss may be sustained for up to a period of 3 years in
the presence of GLP-1 agonist therapy. However, once therapy is discontinued, there is some
regain of weight. There seems to be minimal effect of GLP-1 on energy expenditure per se and
thus the overall negative energy balance seen with GLP-1 therapy is largely a result of
decreased energy intake.
Aim of work Compare safety, feasibility and efficacy of endoscopic ultrasound guided
boutlinum toxin injection and GLP-1 agonists in treatment of obesity.
Patients and Methods Patients Study Design Prospective randomized study.
Study groups 2 Groups: First one: BTA will be injected into gastric antral muscularis propria
under EUS guidance.
Second group: will receive GLP-1 receptor agonist (Liraglutide subcutaneous once daily)
Methods
1. Full written informed consent will be obtained from all patients.
2. Patient demographics.
3. Detailed medical history
4. Complete clinical examination
5. The two methods of intervention will be combined with prescription of several life style
modifications as a 2000 kcal diet in men, or 1800kcal in women and moderate daily
aerobic exercise (at least 30 minutes, 5 times a week) during 4 months and body weight
will be assessed during a 16-week follow-up period.
6. BTA group Esophagogastroduodenoscopy (EGD) will be done to all subjects under conscious
sedation. If no ulceration or retained food, EUS and BTA injection will be performed
under the same sedation. EUS examinations will be performed. BTA injections will be made
via a 25-gauge EUS needle. A ring of five injections will be made into the gastric
antral muscularis propria, 2 to 3 cm proximal to the pylorus. The subjects will receive
20 U at each injection. Subjects will be assessed for complications after recovery from
conscious sedation and, again, by telephone the next day.During a 16-week follow-up
period after BTA injections, subjects will be weighed weekly.
7. GLP1 group GLP-1 receptor agonist (Liraglutide subcutaneous once daily).the
investigators will start by 0.6 mg daily and raise the dose up to 3 mg gradually if
patient tolerated.During a 16 week follow up period, subjects will be weighed weekly.
