A Study of BioEnterics® Intragastric Balloon (BIB®) System to Assist in the Weight Management of Obese Subjects

Study Overview
=================
Brief Summary
-----------------
Safety and effectiveness of the BIB® System in conjunction with a behavior modification program compared to the behavior modification program alone for weight loss in obese subjects.

Official Title
-----------------
Safety and Effectiveness of the BioEnterics® Intragastric Balloon (BIB®) System to Assist in the Weight Management of Obese Subjects

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Device: BioEnterics® Intragastric Balloon
* Other: Behavioral modification


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a BMI ≥ 30 and ≤ 40; Be male or female, between 18 and 65 years of age, inclusive; Have a history of obesity (BMI ≥ 30 kg/m2) for at least 2 years and have failed more conservative weight-reduction alternatives, such as supervised diet, exercise and behavioral modification programs; Be willing to commit to a long-term low calorie (1000-1500 calories/day) supervised diet; Have reasonable weight loss expectations (accept a goal of losing up to 15% of body weight after 26 weeks); Be able to follow requirements outlined in the protocol, including complying with the visit schedule and behavioral modification program, and willing to undergo protocol-specific procedures, e.g., endoscopy, local sedation, general anesthesia, upper gastrointestinal radiography (UGI), electrocardiography (EKG), gastric motility testing, and/or clinical laboratory testing; Must be willing to take prescribed proton pump inhibitors (PPIs)and other medications as prescribed by the investigator; Be able to provide written informed consent and authorization for use and release of Health and Research Study Information; Be willing to use contraception (e.g., birth control pills, condoms, abstinence) and avoid pregnancy during the study if female of child-bearing potential. Exclusion Criteria: Any surgery of the foregut excluding uncomplicated cholecystectomy History or symptoms of gastrointestinal (GI) surgery (excluding uncomplicated appendectomy), GI obstruction, adhesive peritonitis, and/or hiatal hernia (>/= 2 cm); A patulous pyloric channel; History or symptoms of esophageal or GI motility disorders (not just those with <40%) as these patients are particularly susceptible to the development of esophagitis; History or previous symptoms of delayed Gastric Emptying (GE) and/or delayed GE having been documented on a previously performed gastric scintigraphy study or another previously performed diagnostic study such as a UGI x-ray series; Current symptoms of delayed GE; A history of myocardial infarction in the previous 6 months: New York Heart Associate (NYHA) Class III or IV (heart failure) or cardiac arrhythmia (e.g., atrial fibrillation); Anemia defined as a hemoglobin value for females of <11.3 g/dl and for males < 13.0 g/dl; History or symptoms of varices, bowel obstruction, congenital or acquired GI anomalies (e.g., atresias, stenosis, stricture, and/or diverticula), severe renal, hepatic, and/or pulmonary disease; History or symptoms of inflammatory bowel disease, such as Crohn's disease or Ulcerative Colitis; History or symptoms of uncontrolled or unstable thyroid disease; Subjects with a positive test for Helicobacter pylori (H.p.) at screening; subjects may participate in the study if, prior to randomization, they are treated with a pharmacological regimen designed to eradicate their H.p. and subsequently have a negative H.p. breath test indicating that the H.p. has been eradicated History or symptoms in the past 24 months of significant irritable bowel syndrome, peritonitis, active esophagitis, gastritis and/or duodenitis, gastric or duodenal ulceration, GI hemorrhage, or GI bleeding; Type I diabetes; Placement of previous intragastric balloon or similar device; Ongoing treatment with anticoagulants, steroids, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or other medications known to be gastroduodenal mucosal irritants or to reduce GI motility, and/or an unwillingness to discontinue the use of these concomitant medications; Concomitant use of prescription, non-prescription, or over-the-counter weight loss medications or supplements at any time during the study; Evidence of untreated psychiatric or eating disorders, such as major depression, schizophrenia, substance abuse, binge eating disorder, or bulimia; Pregnancy, breast feeding, or intention of becoming pregnant during the study (if female of childbearing potential; Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study; Poor general health, presence of a specific condition, or is in a situation, which in the Evaluating and/or Placing Investigator's opinion may put the subject at significant risk, may confound the study results, may increase the risks associated with endoscopy and/or placement of the BIB, or may interfere significantly with the subject's participation in the study (e.g., HIV, Hepatitis C, or cancer history within the last 5 years)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIB®<br>Receives BioEnterics® Intragastric Balloon Intervention as well as diet and exercise counseling with the Behavioral Modification Intervention. | Device: BioEnterics® Intragastric Balloon<br>* Inflatable balloon inserted into the stomach.<br>* Other names: BIB®;Other: Behavioral modification<br>* Low-calorie diet, food/exercise diary, eating plan, emphasis on exercise<br>|
| Other: Control<br>Control arm receives the Behavioral modification intervention only. | Other: Behavioral modification<br>* Low-calorie diet, food/exercise diary, eating plan, emphasis on exercise<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Excess Weight Loss (%EWL) | The first co-primary effectiveness measure, was mean percent excess weight loss (% EWL) at 9 months (3 months after the balloon was removed for the BIB group). Percent EWL was calculated using the 1983 Met Life tables for determination of ideal body weight, per the protocol-defined primary effectiveness endpoint. Percent EWL was calculated as %EWL= (weight loss divided by excess weight)*100, where Weight loss = Baseline weight - selected follow-up weight, and Excess weight = Baseline weight - ideal weight. | 9 months | 
| Percentage of BIB Treated Participants With Significantly Greater Weight Loss Than the Control Group | The second co-primary effectiveness measure was the percentage of BIB treated participants with significantly greater weight loss than the control group at 9 months. Significantly greater weight loss was defined as ≥ 15% EWL over the mean %EWL of the control group. %EWL= (weight loss divided by excess weight) * 100, where Weight loss = Baseline weight - selected follow-up weight and Excess weight = Baseline weight - ideal weight. Ideal weight was determined by using the 1983 Metropolitan Life Height and Weight Table. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Comorbid Conditions | The percent of participants with a comorbid condition (type 2 diabetes, hypertension, or dyslipidemia) at Week 26 (6 months, balloon removal for BIB group), Week 39 (9 months), and Week 52 (12 months) as compared to baseline. Comorbid conditions were measured and diagnosed by lab tests and vital signs. Type 2 Diabetes was diagnosed if participants' had a Fasting Plasma Glucose (FPG) ≥126 mg/dL, or symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dL. Hypertension was diagnosed if participants' blood pressure measured ≥140 mmHg systolic or ≥90 mmHg diastolic. Dyslipidemia was diagnosed if participants' labs measured: LDL ≥160 mg/dL, Total Cholesterol ≥240 mg/dL, Serum Triglycerides ≥200 mg/DL, HDL <50 mg/dL (male) or <40 mg/dL (female). | Baseline, Week 26, Week 39, Week 52 | 
| Change in Quality of Life (SF-36) | The change in quality of life from baseline to 9 months was measured by the Short Form 36 (SF-36) questionnaire. The SF-36 health survey consists of 36 questions that evaluate 8 discrete domains: Physical Functioning (Physical Func), Social Functioning (Social Func), Bodily Pain, General Health Perceptions (General Health), Vitality, Role limitations due to emotional problems (Role-Emotional), Role limitations due to physical health (Role Physical), and Mental Health. The score for each domain ranges from 0 (poorest health status) to 100 (best health status). The BIB group's mean scores for each SF-36 domain at baseline and week 39 were compared to the control group's mean scores. | Baseline, Week 39 | 
| Change in Quality of Life (IWQOL-Lite) | The change in quality of life from baseline to 12 months was measured by the Impact of Weight on Quality of Life - Lite (IWQOL-Lite) questionnaire. IWQOL-Lite consists of 31 scale items to assess obesity-related quality of life, and total score ranges from 0 (worst) to 100 (best). The BIB group's mean IWQOL-Lite score at baseline, Week 26 (6 months, balloon removal for BIB group), Week 39 (9 months) and Week 52 (12 months) were compared to the control group's mean scores at the same timepoints. | Baseline, Week 26, Week 39, Week 52 | 
| Change in Participant Depression (Beck Depression Inventory II) | Participants were assessed for depression using the Beck Depression Inventory II (BDI-II) questionnaire. The BDI-II consists of 21 questions to measure depressive symptoms and severity. The overall score ranges from 0-63, where higher total scores indicate more severe depressive symptoms. A total score of 0-13 is considered a minimal range, 14-19 is mild, 20-28 is moderate and 29-63 is interpreted as severe depressive symptoms. The mean BDI-II score for the BIB and control groups were assessed at baseline and at key timepoints: Week 26 (month 6, balloon removal for BIB group), Week 39 (month 9), and Week 52 (month 12, study completion). | Baseline, Week 26, Week 39, Week 52 |