The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial

Efficacy and Safety of EndoBar Bariatric Embolization for Weight Management in People With Obesity

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03185949

Acronym

LOSEIT

Enrollment

Registered

2017-06-14

Start date

2017-02-08

Completion date

2018-12-01

Last updated

2022-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Morbid

Keywords

Obesity, Embolization, Left Gastric Artery

Brief summary

To evaluate the efficacy and safety of the Endobar gastric embolization system for the treatment of obesity before continuing to a larger Pivotal Trial. Investigational Device The investigational device in this clinical study is the Endobar Infusion Catheter System - a disposable system consisting of an occlusion balloon catheter, a Smart Manifold delivery system. Study Design/Planned Number of Subjects This study is a prospective, sham controlled, single-blind 12-month trial with 1:1 randomization. A maximum of 40 subjects (obese men and women who have a body mass index (BMI) of 35.0-50.0 kg/m2) will be enrolled in the study. Eligible subjects will be randomized to treatment with Endobar Therapy (n = 20) or sham procedure control (n = 20). Endobar Therapy involves catheter-based embolization of the left gastric artery. All subjects in both Endobar Therapy and Sham Control groups will receive Lifestyle Therapy (behavioral and diet education). At the end of 6 months all subjects randomized to the Sham Control group will receive catheter-based embolization of the left gastric artery. Both Endobar Therapy and Sham Control crossover to Endobar Therapy groups will be followed for a total of 12 months. Study Duration The duration of the study is expected to last approximately 18 months from the first enrollment . An additional 12 months to the study closeout after the last follow-up.

Detailed description

STUDY OBJECTIVES Objective The objective of this study is to conduct a sham controlled randomized trial to evaluate the efficacy and safety of the Endobar System for the treatment of obesity. Efficacy, Safety, and secondary outcomes will be evaluated at 6 and 12 months to allow expansion of the investigation into a larger, pivotal clinical study. Study Design This is a prospective randomized, single blind, active treatment and sham controlled, single-center trial . After the informed consent and screening process are completed, all subjects who are eligible and wish to participate in the study will undergo baseline testing. Those who complete baseline testing will be randomized to either Endobar Therapy (ET) or Sham Treatment (ST) for 52 weeks. Both groups will be given lifestyle therapy for weight loss, which involves treatment with a behavioral education weight loss program delivered as 19 individual sessions in person over 52 weeks. Endobar Therapy involves catheter-based embolization of the left gastric artery. After 26 weeks, the ET group will continue to be monitored for an addition 26 weeks and the ST subjects will be given ET and monitored for 26 weeks. The duration of the entire study will be 52 weeks.

Interventions

DEVICEEndobar Infusion Catheter System

Bariatric embolization with microspheres using Endobar Infusion Catheter System

BEHAVIORALBehavioral therapy

Healthy diet and exercise

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Outcomes Assessor)

Masking description

* Interventional Group: These subjects will undergo catheter-based embolization. * Sham Control Group: These subjects will not undergo femoral artery catheterization. Instead, lidocaine will be injected subcutaneously at the femoral artery site in the Sham Control group. Since all patients will have received at least sedation, they will not be aware of what has been done, and thus be blind to their treatment assignment

Intervention model description

This study is a prospective, sham controlled, single-blind 12-month trial with 1:1 randomization. A maximum of 40 subjects (obese men and women who have a body mass index (BMI) of 35.0-50.0 kg/m2) will be enrolled in the study. Eligible subjects will be randomized to treatment with Endobar Therapy (n = 20) or sham procedure control (n = 20). Endobar Therapy involves catheter-based embolization of the left gastric artery. All subjects in both Endobar Therapy and Sham Control groups will receive Lifestyle Therapy (behavioral and diet education). At the end of 6 months all subjects randomized to the Sham Control group will receive catheter-based embolization of the left gastric artery. Both Endobar Therapy and Sham Control crossover to Endobar Therapy groups will be followed for a total of 12 months

Eligibility

Sex/Gender

ALL

Age

21 Years to 66 Years

Healthy volunteers

Inclusion criteria

* • BMI 35.0-50.0 kg/m2 at time of screening * Women of childbearing potential must agree to use at least one form of birth control (prescription hormonal contraceptives, diaphragm, IUD, condoms with or without spermicide, or voluntary abstinence) from time of study enrollment through study exit. * Willing and able to provide informed consent

Exclusion criteria

* • Previous bariatric, gastric pancreatic, hepatic, and/or splenic surgery * History of duodenal or gastric ulcers or regularly taking medications (therapy \>1 day per week) that can cause ulcers (e.g., non-steroidal anti-inflammatory drugs) * Prior radiation to the upper abdomen * Prior embolization to the stomach, spleen or liver * Portal venous hypertension * Active H. pylori infection * Uncontrolled hypertension (\> 160/100 with or without medication). * Diabetes (determined by medical history, fasting blood glucose or results of an oral glucose tolerance test) * Serum triglyceride \> 400 mg/dL at screening. * Class 4 or 5 surgical risk based on standard ASA criteria (Saklad M. Grading of patients for surgical procedures. Anesthesiol. 1941; 2:281-4). * Severe pulmonary or cardiovascular disease defined as a history or evidence of serious cardiovascular disease, including myocardial infarction, acute coronary syndrome, coronary revascularization, heart failure requiring medications, history of sudden cardiac death, or NYHA (New York Heart Association) class III or IV heart failure (defined below): * Class III: patients with marked limitation of activity; they are comfortable only at rest. * Class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on discomfort and symptoms occur at rest. * Coagulation disorders (platelets \< 100,000, PT \> 2 seconds above control or INR \> 1.5 at screening). * Anemia (Hb \< 10.0 g/dL) at screening. * Malignancy in the last 5 years (except for non-melanoma skin cancer). * Evidence of other significant organ system dysfunction (e.g. cirrhosis, renal failure) * Pregnant or lactating. * History of substance abuse in last 3 years. * Thyroid Stimulating Hormone (TSH) \>2.0 x upper limit of normal at screening. * Taking prescription or over-the-counter medications for weight loss in the last 3 months before screening, or planning to participate in a commercial weight loss program in the next 5 years. * Taking diuretic medication for congestive heart failure or edema. * Evidence of significant mucosal inflammation, ulceration or ischemia detected on endoscopy, and those with unsuitable left gastric anatomy as judged by the study site physician will be excluded * Psychiatric illness that could affect compliance with the study, as judged by the site principle investigator. * Unable to complete screening requirements (compliance with visits and dietary record) * Taking medication once or more per week that causes weight gain (e.g. atypical antipsychotics, monoamine oxidase inhibitors, lithium, selected anticonvulsants, tamoxifen, glucocorticoids) * Chronic abdominal pain that would potentially complicate management. * Unstable weight (\>3% change; self-reported) over the previous 2 months at time of screening. * Subjects whom the site investigator, research team, or the study medical monitor feel is not able to participate in the study for any reason, including poor general health or unable/unwilling to follow the study protocol.

Design outcomes

Primary

Measure	Time frame	Description
Weight Loss	1) 6 months post-procedure/sham and 2) 12 months post-procedure	1. Difference in percent total body weight (% TBWL) loss at 6 months between the Sham Control and Endobar Therapy groups. This is calculated as the difference in body weight from baseline to 6 months, relative to the baseline weight (i.e, initial weight - 6 month weight / initial weight) x 100%). The mean (i.e., average) total body weight loss of both groups was compared to assess whether there was a meaningful difference. 2. Percent total body weight loss (%TBWL) at 12 months in the group randomized to the initial Endobar Therapy alone. This is calculated as the difference in body weight from baseline to 12 months, relative to the baseline weight (i.e, initial weight - 12 month weight / initial weight) x 100%).
Number of Patients With Adverse Events	12 months post-randomization	The Incidence of device-, procedure- and therapy-related adverse events up to 12 months post-procedure.
Absolute Weight Loss (kg)	6 months post-procedure/sham and 12 months post-procedure	6-month change: The absolute difference in the initial and 6-month weight (kg) (i.e., initial - 6 month weight). These changes were averaged for each group and compared between the two groups to assess whether there was a meaningful difference. 12-month change: The absolute difference in the initial and 12-month weight (kg) (i.e., initial - 12 month weight).

Secondary

Measure	Time frame	Description
Percent Excess Body Weight (%EBWL) Loss	1) 6 months post-procedure/sham and 2) 12 months post-procedure	Percent excess body weight loss (% EBWL) is calculated by dividing the absolute weight loss divided by baseline excess weight and multiplying by 100% (i.e., excess weight / initial weight x 100%). Excess weight is defined as the difference between current weight and ideal weight. %EBWL was calculated for the following time points: 1. 6 months: absolute weight loss was the difference from baseline to 6 months. %EBWL was averaged for each group and compared to assess whether there was a meaningful difference between the groups. 2. 12 months: absolute weight loss was the difference from baseline to 12 months. Note, excess weight was determined from ideal body weights based on a BMI=25 kg/m2.
6 and 12 Month Change in Blood Pressure	6 months post-procedure/sham and 12 months post-procedure	Change in absolute blood pressure levels from baseline to 6 months for both groups and baseline to 12 months for the initial treatment group. Unit of Measure: mmHg
Number of Patients With Weight Loss ≥5%	6 months post-procedure/sham	Proportion of subjects who achieve ≥5% total body weight loss from baseline vs. those who do not
6 Month Change in Lipids	6 months post-procedure/sham	6-month change (from baseline) in lipids for both groups. Unit of Measure: mg/dL

Other

Measure	Time frame	Description
Change in Volume of Meal Test Consumed to Achieve Satiation: Satiation Drink Test.	[Time Frame: 6-12 months]	Change in satiety and other parameters associated with this test Unit of Measure: numerical scale from 0-5
Ghrelin Levels	[Time Frame: 6-12 months]	Unit of Measure: pg/mL
Gastric Motility/Emptying	[Time Frame: 6-12 months]	Unit of Measure: (t 1/2) in minutes
Results From Endoscopy	12 months	Photos and clinical reports analyzed
Glucagon-like Peptide 1 Concentrations	[Time Frame: 6-12 months]	Changes in Glucagon-like peptide 1 concentrations Unit of Measure: pg/mL
Oral Glucose Tolerance and Insulin Sensitivity	[Time Frame: 6-12 months]	Changes in OGTT and Insulin Sensitivity Unit of measure:milligrams/deciliter (mg/dL)
Insulin Sensitivity	[Time Frame: 6-12 months]	Unit of measure: mg/min
Changes in Mood (Depression/Anxiety)	[Time Frame: 6-12 months]	Unit of Measure: Beck Depression Index
Change in Quality-of-life	[Time Frame: 6-12 months]	Change in the subdomains and overall Quality of Life Unit of Measure: IWQOL
Change in Eating Behavior	[Time Frame: 6-12 months]	Unit of Measure: Eating Questionnaire Scores

Countries

Czechia

Participant flow

Participants by arm

Arm	Count
Sham Control Lidocaine injected at the femoral artery site. This patients will undergo behavioral therapy for 6 months and will crossover and will receive bariatric embolization. Endobar Infusion Catheter System: Bariatric embolization with microspheres using Endobar Infusion Catheter System Behavioral therapy: Healthy diet and exercise	22
Percutaneous Transcathether Embolotherapy In patients randomized to intervention bariatric embolization will be performed using Endobar Infusion Catheter System. After procedure patients will undergo behavioral therapy Endobar Infusion Catheter System: Bariatric embolization with microspheres using Endobar Infusion Catheter System Behavioral therapy: Healthy diet and exercise	22
Total	44

Withdrawals & dropouts

Period	Reason	FG000	FG001
ITT Analysis	Withdrawal by Subject	4	3
PP Analysis	Failed/Incomplete LGA embolization	0	2
PP Analysis	Protocol Violation	2	2

Baseline characteristics

Characteristic	Sham Control	Percutaneous Transcathether Embolotherapy	Total
Age, Continuous	44.7 years STANDARD_DEVIATION 9.4	46.4 years STANDARD_DEVIATION 10.3	45.55 years STANDARD_DEVIATION 9.7
BMI (kg/m^2)	38.93 kg/m^2 STANDARD_DEVIATION 3.8	40.2 kg/m^2 STANDARD_DEVIATION 3.7	39.58 kg/m^2 STANDARD_DEVIATION 3.8
Race and Ethnicity Not Collected	—	—	0 Participants
Region of Enrollment Czechia	22 participants	22 participants	44 participants
Sex: Female, Male Female	21 Participants	15 Participants	36 Participants
Sex: Female, Male Male	1 Participants	7 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 34
other Total, other adverse events	0 / 20	5 / 34
serious Total, serious adverse events	0 / 20	1 / 34

Outcome results

Primary

Absolute Weight Loss (kg)

6-month change: The absolute difference in the initial and 6-month weight (kg) (i.e., initial - 6 month weight). These changes were averaged for each group and compared between the two groups to assess whether there was a meaningful difference. 12-month change: The absolute difference in the initial and 12-month weight (kg) (i.e., initial - 12 month weight).

Time frame: 6 months post-procedure/sham and 12 months post-procedure

Population: The ITT is representative of all randomized subjects who underwent either the sham or PTE, regardless of follow-up compliance. The PP represents subjects treated and compliant to study treatment and follow-up visits per the protocol, no major protocol deviations, or protocol violations. Note for 12 months post-procedure, only those initially randomized to PTE were followed for 12 months. The sham control, pursuant to the study protocol, were only followed for 6 months post-procedure.

Arm	Measure	Group	Value (MEAN)
Sham Control	Absolute Weight Loss (kg)	6 Months: ITT Population	3.0 kilograms
Sham Control	Absolute Weight Loss (kg)	6 Months: PP Population	9.4 kilograms
Percutaneous Transcatheter Embolotherapy	Absolute Weight Loss (kg)	12 Months: PP	9.3 kilograms
Percutaneous Transcatheter Embolotherapy	Absolute Weight Loss (kg)	6 Months: ITT Population	7.4 kilograms
Percutaneous Transcatheter Embolotherapy	Absolute Weight Loss (kg)	6 Months: PP Population	1.9 kilograms
Percutaneous Transcatheter Embolotherapy	Absolute Weight Loss (kg)	12 Months: ITT	7.8 kilograms

Primary

Number of Patients With Adverse Events

The Incidence of device-, procedure- and therapy-related adverse events up to 12 months post-procedure.

Time frame: 12 months post-randomization

Population: Safety Population (i.e. any participant who consented to be in the study and underwent either the sham or therapy procedure). Each count indicates a participant who reported experiencing the described event.

Arm	Measure	Group	Value (NUMBER)
Sham Control	Number of Patients With Adverse Events	Epigastring Pain	3 participants
Sham Control	Number of Patients With Adverse Events	Nausea	4 participants
Sham Control	Number of Patients With Adverse Events	Epigastric Pressure	0 participants
Sham Control	Number of Patients With Adverse Events	Vomitting	5 participants
Sham Control	Number of Patients With Adverse Events	Asymptomatic Ulcers	0 participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Adverse Events	Vomitting	7 participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Adverse Events	Asymptomatic Ulcers	5 participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Adverse Events	Epigastring Pain	4 participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Adverse Events	Epigastric Pressure	3 participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Adverse Events	Nausea	7 participants

Primary

Weight Loss

1. Difference in percent total body weight (% TBWL) loss at 6 months between the Sham Control and Endobar Therapy groups. This is calculated as the difference in body weight from baseline to 6 months, relative to the baseline weight (i.e, initial weight - 6 month weight / initial weight) x 100%). The mean (i.e., average) total body weight loss of both groups was compared to assess whether there was a meaningful difference. 2. Percent total body weight loss (%TBWL) at 12 months in the group randomized to the initial Endobar Therapy alone. This is calculated as the difference in body weight from baseline to 12 months, relative to the baseline weight (i.e, initial weight - 12 month weight / initial weight) x 100%).

Time frame: 1) 6 months post-procedure/sham and 2) 12 months post-procedure

Arm	Measure	Group	Value (MEAN)
Sham Control	Weight Loss	6 Months: ITT Population	2.8 Percent change
Sham Control	Weight Loss	6 Months: PP Population	1.8 Percent change
Percutaneous Transcatheter Embolotherapy	Weight Loss	6 Months: ITT Population	6.4 Percent change
Percutaneous Transcatheter Embolotherapy	Weight Loss	6 Months: PP Population	8.3 Percent change
Percutaneous Transcatheter Embolotherapy	Weight Loss	12 Months: ITT Population	6.5 Percent change
Percutaneous Transcatheter Embolotherapy	Weight Loss	12 Months: PP Population	9.3 Percent change

Secondary

6 and 12 Month Change in Blood Pressure

Change in absolute blood pressure levels from baseline to 6 months for both groups and baseline to 12 months for the initial treatment group. Unit of Measure: mmHg

Time frame: 6 months post-procedure/sham and 12 months post-procedure

Arm	Measure	Group	Value (MEAN)
Sham Control	6 and 12 Month Change in Blood Pressure	6 Months: Systolic Blood Pressure	-3.7 mmHg
Sham Control	6 and 12 Month Change in Blood Pressure	6 Months: Diastolic Blood Pressure	-0.6 mmHg
Percutaneous Transcatheter Embolotherapy	6 and 12 Month Change in Blood Pressure	6 Months: Systolic Blood Pressure	2.3 mmHg
Percutaneous Transcatheter Embolotherapy	6 and 12 Month Change in Blood Pressure	6 Months: Diastolic Blood Pressure	2.8 mmHg
Percutaneous Transcatheter Embolotherapy	6 and 12 Month Change in Blood Pressure	12 Months: Systolic Blood Pressure	-1.8 mmHg
Percutaneous Transcatheter Embolotherapy	6 and 12 Month Change in Blood Pressure	12 Months: Diastolic Blood Pressure	-9.7 mmHg

Secondary

6 Month Change in Lipids

6-month change (from baseline) in lipids for both groups. Unit of Measure: mg/dL

Time frame: 6 months post-procedure/sham

Arm	Measure	Group	Value (MEAN)	Dispersion
Sham Control	6 Month Change in Lipids	Low-Density Lipoprotein (LDL) - Baseline	1.23 mmol/L	Standard Deviation 0.74
Sham Control	6 Month Change in Lipids	High-Density Lipoprotein (HDL) - Baseline	1.23 mmol/L	Standard Deviation 0.28
Sham Control	6 Month Change in Lipids	High-Density Lipoprotein (HDL) - 6 Months	1.26 mmol/L	Standard Deviation 0.21
Sham Control	6 Month Change in Lipids	Total Cholesterol - 6 Months	4.99 mmol/L	Standard Deviation 0.7
Sham Control	6 Month Change in Lipids	Triglyceride - Baseline	1.29 mmol/L	Standard Deviation 0.52
Sham Control	6 Month Change in Lipids	Low-Density Lipoprotein (LDL) - 6 Months	1.26 mmol/L	Standard Deviation 0.64
Sham Control	6 Month Change in Lipids	Triglyceride - 6 Months	1.41 mmol/L	Standard Deviation 0.74
Sham Control	6 Month Change in Lipids	Total Cholesterol - Baseline	5.23 mmol/L	Standard Deviation 0.81
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	Triglyceride - 6 Months	1.40 mmol/L	Standard Deviation 1.14
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	Total Cholesterol - Baseline	4.69 mmol/L	Standard Deviation 0.71
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	High-Density Lipoprotein (HDL) - Baseline	1.29 mmol/L	Standard Deviation 0.32
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	Total Cholesterol - 6 Months	4.94 mmol/L	Standard Deviation 0.71
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	Low-Density Lipoprotein (LDL) - Baseline	1.29 mmol/L	Standard Deviation 0.69
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	Low-Density Lipoprotein (LDL) - 6 Months	1.28 mmol/L	Standard Deviation 0.68
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	High-Density Lipoprotein (HDL) - 6 Months	1.28 mmol/L	Standard Deviation 0.26
Percutaneous Transcatheter Embolotherapy	6 Month Change in Lipids	Triglyceride - Baseline	1.34 mmol/L	Standard Deviation 0.76

Secondary

Number of Patients With Weight Loss ≥5%

Proportion of subjects who achieve ≥5% total body weight loss from baseline vs. those who do not

Time frame: 6 months post-procedure/sham

Population: The intention-to-treat (ITT) and per-protocol (PP) groups. The ITT population is representative of all randomized subjects who underwent either the sham or the therapeutic procedure, regardless of when they withdrew from the study or not post-procedure. The PP population represents subjects treated and complaint to study treatment and follow-up visits per the protocol, no major protocol deviations, or protocol violations.

Arm	Measure	Group	Category	Value (COUNT_OF_PARTICIPANTS)
Sham Control	Number of Patients With Weight Loss ≥5%	PP Population	≥ 5%	2 Participants
Sham Control	Number of Patients With Weight Loss ≥5%	ITT Population	< 5%	14 Participants
Sham Control	Number of Patients With Weight Loss ≥5%	ITT Population	≥ 5%	4 Participants
Sham Control	Number of Patients With Weight Loss ≥5%	PP Population	< 5%	14 Participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Weight Loss ≥5%	PP Population	< 5%	6 Participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Weight Loss ≥5%	PP Population	≥ 5%	9 Participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Weight Loss ≥5%	ITT Population	≥ 5%	9 Participants
Percutaneous Transcatheter Embolotherapy	Number of Patients With Weight Loss ≥5%	ITT Population	< 5%	10 Participants

Secondary

Percent Excess Body Weight (%EBWL) Loss

Percent excess body weight loss (% EBWL) is calculated by dividing the absolute weight loss divided by baseline excess weight and multiplying by 100% (i.e., excess weight / initial weight x 100%). Excess weight is defined as the difference between current weight and ideal weight. %EBWL was calculated for the following time points: 1. 6 months: absolute weight loss was the difference from baseline to 6 months. %EBWL was averaged for each group and compared to assess whether there was a meaningful difference between the groups. 2. 12 months: absolute weight loss was the difference from baseline to 12 months. Note, excess weight was determined from ideal body weights based on a BMI=25 kg/m2.

Time frame: 1) 6 months post-procedure/sham and 2) 12 months post-procedure

Arm	Measure	Group	Value (MEAN)
Sham Control	Percent Excess Body Weight (%EBWL) Loss	6 Months: ITT Population	8.6 EBWL %
Sham Control	Percent Excess Body Weight (%EBWL) Loss	6 Months: PP Population	5.4 EBWL %
Percutaneous Transcatheter Embolotherapy	Percent Excess Body Weight (%EBWL) Loss	6 Months: ITT Population	17.1 EBWL %
Percutaneous Transcatheter Embolotherapy	Percent Excess Body Weight (%EBWL) Loss	6 Months: PP Population	22.3 EBWL %
Percutaneous Transcatheter Embolotherapy	Percent Excess Body Weight (%EBWL) Loss	12 Months: ITT Population	17.3 EBWL %
Percutaneous Transcatheter Embolotherapy	Percent Excess Body Weight (%EBWL) Loss	12 Months: PP Population	21.8 EBWL %

Other Pre-specified