EMPOWER Clinical Trial: Vagal Blocking for Obesity Control

• Sponsor: ReShape Lifesciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00521079
• Collaborator: (none)
• Enrollment: 294
• Locations: 15
• Arms: 2
• Duration (Months): 129
• Patients Per Site: 19.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a randomized multi-center study being done to measure the ability of a new medical device, Maestro System, to safely reduce body weight over five years in people who are considered obese.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Device: Therapy ON; Device: Therapy OFF	N/A

Detailed Description

The Maestro System is a neuromodulation system that consists of implantable and external components.

Implantable components: two leads (one electrode each for the anterior and posterior intra-abdominal vagal nerve trunks) that are connected to an implantable neuroregulator.

External components: one programmable, battery-powered, ambulatory external controller connected via a small, flexible cable to a cutaneous transmit coil that is positioned externally over the neuroregulator. A clinician programmer that transmits information to the controller and uploads data from the controller.

All non-diabetic subjects will be randomized in a 2:1 allocation to therapy ON or therapy OFF groups. All type 2 diabetes mellitus subjects will be randomized in a 1:1 allocation to therapy ON or therapy OFF groups.

All subjects will receive blinded therapy through the 12-month follow-up visit. All subjects will participate in a medical weight management program.

Study Design

• Study Type: Interventional
• Actual Enrollment: 294 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: EMPOWER Clinical Trial: Vagal Blocking for Obesity Control
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: May 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vBloc Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).	Device: Therapy ON; Intermittent, programmable, intra-abdominal vagal blocking device that delivers therapy (Therapy ON); Other Names: Maestro System
Sham Comparator: Placebo Subjects implanted with a functional Maestro System device that does NOT deliver therapy (Therapy OFF).	Device: Therapy OFF; Active intra-abdominal placebo device that delivers no therapy (Therapy OFF); Other Names: Maestro System

Outcome Measures

Primary Outcome Measures

1. Percentage of Excess Weight Loss (EWL) With the Maestro System [Baseline and 1 Year]

   Observe at least a 10% greater percentage excess weight loss (%EWL) with vBloc therapy delivered by the Maestro System compared to sham 12 months following randomization using MetLife Method (ideal body weight is calculated based on Metropolitan Height and Weight Tables)

2. Rate of System and Procedure-related Serious Adverse Events (SAEs). [1 Year]

   To estimate the rate of serious, system- and procedure-related adverse events associated with the Maestro System.

Secondary Outcome Measures

1. Percentage of Participants Achieving 25% Excess Weight Loss (%EWL) [Baseline and 1 Year]

   To evaluate the percentage of participants achieving 25% excess weight loss from baseline (implant) to 12 months between treatment groups.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Informed consent.

2. Body mass index (BMI) ≥ 40 kg/m2 to 45 kg/m2 or BMI ≥ 35 kg/m2 to 39.9 kg/m2 with one or more obesity related co-morbid condition. Co-morbid conditions may include one or more of the following:

• Type 2 diabetes mellitus (note: type 2 diabetics are allowed at selected centers only, see Inclusion criterion #5)

• Hypertension as defined by systolic pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg a) treated or untreated with systolic ≥140 mmHg or diastolic ≥90 mmHg or

1. treated with systolic <140 mmHg and diastolic <90 mmHg

• Dyslipidemia as defined by total cholesterol ≥200 or LDL ≥130 a) treated or untreated with total cholesterol ≥200 or LDL ≥130 or b) treated with total cholesterol <200 or LDL <130

• Sleep apnea syndrome (confirmed by overnight p02 studies)

• Obesity related cardiomyopathy

1. Females or males Note: females of child-bearing potential must have a negative urine pregnancy test at Screen and also within 14 days of implant procedure followed by physician-approved contraceptive regimen for the duration of the study period.

2. 18-65 years of age inclusive.

3. Type 2 diabetes mellitus subjects (at selected centers, limited to approximately 34 subjects) with:

• Glycosylated hemoglobin (Hb A1c) 6.5 - 9 % inclusive at screening visit.

• Onset: 10 years or less since initial diagnosis.

• Stable treatment regimen: no change in oral hypoglycemic treatment regimen within past 3 months.

• Currently not using insulin therapy, GLP-1 receptor agonists (e.g., exenatide), or DPP-4 inhibitors (e.g., sitagliptin) for diabetes treatment and have not been on these treatments in the past 6 months.

• Creatinine within normal reference range.

• No history of proliferative retinopathy.

• No history of peripheral neuropathy.

• No history of autonomic neuropathy.

• No history of coronary artery disease, with or without angina pectoris.

• No history of peripheral vascular disease.

1. Failure to respond to supervised diet/exercise program(s) in which the subject was engaged for at least 6 months within the last five years.

2. Ability to complete all study visits and procedures.

Exclusion criteria

1. Concurrent chronic pancreatic disease.

2. History of Crohn's disease and/or ulcerative colitis.

3. History of bariatric surgery, fundoplication, gastric resection or major upper-abdominal surgery (acceptable surgeries include cholecystectomy, hysterectomy).

4. History of pulmonary embolism or blood coagulation disorders.

5. Clinically significant hiatal hernias known from subject's medical record as or determined by upper endoscopy prior to implant if they have not had one done during the previous 6 months that specifically reported on the presence or absence of hiatal hernia making reference to the Z-line and/or diaphragmatic notch, in order to rule out subjects with hiatal hernia that may require surgical repair (to support exclusion criterion #7).

6. Current portal hypertension and/or esophageal varices.

7. Intra-operative exclusion: hiatal hernia requiring surgical repair or extensive dissection at esophagogastric junction at time of surgery.

8. Treatment with weight-loss prescription drug therapy within the prior three months and the use of prescription drug therapy or the use over-the-counter weight loss preparations for the duration of the trial.

9. Smoking cessation within the prior six months.

10. Known genetic cause of obesity (e.g., Prader-Willi Syndrome).

11. Overall sustained reduction of more than 10% of body weight in the previous 12 months.

12. Physician-prescribed pre-operative diet with intent to lose weight prior to surgery (note: a) study subject may continue any personal diet they were on prior to study enrollment [see exclusion criterion #24] b) standardized EMPOWER weight management program to be initiated in all subjects at time of activation, approximately two weeks after implant)

13. Current type 1 diabetes mellitus (DM).

14. Current or recent history (within 12 months) of ongoing bulimia.

15. Current alterations in treatment for thyroid disorders (stable treatment regimen for prior three months acceptable).

16. Current alterations in treatment for epilepsy (stable treatment regimen for prior six months acceptable).

17. Current treatment for peptic ulcer disease (previous history acceptable).

18. Chronic (more than 4 weeks of daily use) treatment with narcotic analgesic drug regimens (treatment with non-steroidal anti-inflammatory drugs acceptable).

19. Current alterations in treatment regimens of anti-cholinergic drugs, including tricyclic antidepressants (stable treatment regimen for prior six months acceptable).

20. Current medical condition that, in the opinion of the investigator, would make subject unfit for surgery under general anesthesia or that would be exacerbated by intentional weight loss. Some examples include diagnosis of cancer, recent heart attack, recent stroke or recent serious trauma.

21. Presence of permanently implanted electrical powered medical device or implanted gastrointestinal device or prosthesis (e.g., pacemakers, implanted defibrillators, neurostimulators etc.).

22. Planned or contemplated use of Magnetic Resonance Imaging (MRI) or oncological radiation during the course of the trial.

23. Significant psychiatric disorders that, in the opinion of the investigator, may interfere with subject's ability to follow study procedures and/or instructions.

24. Current, active member of an organized weight loss program (e.g., Weight Watchers, TOPS).

25. Current participant in another weight loss study or other clinical trials.

26. Have a friend or family member who is currently participating or is planning to participate in this clinical trial.

27. Patient reported:

• inability to walk for about 10 minutes without stopping,

• feeling of pain in chest when doing physical activity,

• feeling of pain in chest when not doing physical activity. Note: unless pain in chest in known to be related to upper gastrointestinal disorders such as gastroesophageal reflux disease or heartburn.

1. Clinically significant cardiac rhythm disorder that requires either medical and/or surgical intervention (e.g., paroxysmal or chronic atrial fibrillation).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth (formerly Scottsdale Bariatric Center)	Scottsdale	Arizona	United States	85258
2	Scripps Clinic	La Jolla	California	United States	92037
3	University of California, Irvine Medical Center	Orange	California	United States	92868
4	Stanford University Medical Center	Stanford	California	United States	94305
5	Cleveland Clinic - Florida	Weston	Florida	United States	33331
6	Johns Hopkins	Baltimore	Maryland	United States	21224
7	Tufts New England Medical Center	Boston	Massachusetts	United States	02111
8	University of Minnesota	Minneapolis	Minnesota	United States	55455
9	Mayo Clinic	Rochester	Minnesota	United States	55905
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
11	Cleveland Clinic - Ohio	Cleveland	Ohio	United States	44195
12	Oregon Health & Science University	Portland	Oregon	United States	97239-3098
13	Virginia Commonwealth University	Richmond	Virginia	United States	23298
14	Institute of Weight Control	Sydney	New South Wales	Australia	2153
15	Adelaide Bariatric Center - Flinders Private Hospital	Bedford Park	South Australia	Australia	5042

Sponsors and Collaborators

• ReShape Lifesciences

Investigators

• Principal Investigator: Charles J Billington, MD, VA Medical Center, Minneapolis, MN / University of Minnesota
• Principal Investigator: Michael Sarr, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ReShape Lifesciences
• ClinicalTrials.gov Identifier: NCT00521079
• Other Study ID Numbers: D00343-000
• First Posted: Aug 27, 2007
• Last Update Posted: Aug 24, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by ReShape Lifesciences: Obesity; Bariatric surgery; Excess weight loss; Vagus nerve; Vagal blocking; vBloc(TM) therapy
• Additional relevant MeSH terms: Obesity

Study Results

Participant Flow

Arm/Group Title	vBloc	Placebo
Arm/Group Description	Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).	Subjects implanted with a functional Maestro System device that does NOT deliver therapy (Therapy OFF).
Period Title: Overall Study
STARTED	192	102
Surgical Roll-In	9	5
COMPLETED	178	97
NOT COMPLETED	14	5

Baseline Characteristics

Arm/Group Title	vBloc	Placebo	Total
Arm/Group Description	Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).	Subjects implanted with a functional Maestro System device that does NOT deliver therapy (Therapy OFF).	Total of all reporting groups
Overall Participants	183	97	280
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	183 100%	97 100%	280 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (9.7)	45.6 (10.6)	45.7 (10)
Sex: Female, Male (Count of Participants)
Female	165 90.2%	83 85.6%	248 88.6%
Male	18 9.8%	14 14.4%	32 11.4%
Region of Enrollment (participants) [Number]
United States	142 77.6%	77 79.4%	219 78.2%
Australia	41 22.4%	20 20.6%	61 21.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Excess Weight Loss (EWL) With the Maestro System
Description	Observe at least a 10% greater percentage excess weight loss (%EWL) with vBloc therapy delivered by the Maestro System compared to sham 12 months following randomization using MetLife Method (ideal body weight is calculated based on Metropolitan Height and Weight Tables)
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vBloc	Placebo
Arm/Group Description	Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).	Subjects implanted with a functional Maestro System device that does NOT deliver therapy (Therapy OFF).
Measure Participants	165	88
Mean (Standard Error) [Percentage of excess weight loss]	17 (2)	16 (2)

2. Primary Outcome

Title	Rate of System and Procedure-related Serious Adverse Events (SAEs).
Description	To estimate the rate of serious, system- and procedure-related adverse events associated with the Maestro System.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vBloc	Placebo
Arm/Group Description	Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).	Subjects implanted with a functional Maestro System device that does NOT deliver therapy (Therapy OFF).
Measure Participants	192	102
Number [Events]	6	3

3. Secondary Outcome

Title	Percentage of Participants Achieving 25% Excess Weight Loss (%EWL)
Description	To evaluate the percentage of participants achieving 25% excess weight loss from baseline (implant) to 12 months between treatment groups.
Time Frame	Baseline and 1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	vBloc	Placebo
Arm/Group Description	Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).	Subjects implanted with a functional Maestro System device that does NOT deliver therapy (Therapy OFF).
Measure Participants	183	97
Number [Percentage of subjects]	22	25

Adverse Events

Adverse Event Reporting Description	Includes roll-in subjects.
Arm/Group Title	vBloc		Placebo
Arm/Group Description	Subjects implanted with a functional Maestro System device that delivers therapy (Therapy ON).		Subjects implanted with a functional Maestro System device that does NOT delivers therapy (Therapy OFF).
All Cause Mortality
	vBloc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	vBloc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/192 (12%)		12/102 (11.8%)
Cardiac disorders
Cardiac abnormality	1/192 (0.5%)	1	0/102 (0%)	0
Hypertension	0/192 (0%)	0	1/102 (1%)	1
Gastrointestinal disorders
Pain abdominal	3/192 (1.6%)	3	0/102 (0%)	0
Large bowel dysfunction	0/192 (0%)	0	1/102 (1%)	1
General disorders
Cold/flu/respiratory tract infection	1/192 (0.5%)	1	0/102 (0%)	0
Other	8/192 (4.2%)	8	6/102 (5.9%)	6
Pain other	1/192 (0.5%)	1	0/102 (0%)	0
Reaction to medicines	1/192 (0.5%)	1	0/102 (0%)	0
Hepatobiliary disorders
Gallbladder disease	1/192 (0.5%)	1	0/102 (0%)	0
Infections and infestations
Infection neuroregulator site	2/192 (1%)	2	1/102 (1%)	1
Infection other	1/192 (0.5%)	1	1/102 (1%)	1
Reproductive system and breast disorders
Bleeding other	1/192 (0.5%)	1	0/102 (0%)	0
Skin and subcutaneous tissue disorders
Pain neuroregulator site	1/192 (0.5%)	1	1/102 (1%)	1
Surgical and medical procedures
Incision pain incision site	1/192 (0.5%)	1	0/102 (0%)	0
Lead impedance high	0/192 (0%)	0	1/102 (1%)	1
Neuroregulator malfunction	1/192 (0.5%)	1	0/102 (0%)	0
Other (Not Including Serious) Adverse Events
	vBloc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/192 (76%)		70/102 (68.6%)
Cardiac disorders
Edema	9/192 (4.7%)	9	3/102 (2.9%)	3
Gastrointestinal disorders
Bloating Abdominal	10/192 (5.2%)	10	7/102 (6.9%)	8
Constipation	32/192 (16.7%)	38	12/102 (11.8%)	12
Diarrhea	23/192 (12%)	29	15/102 (14.7%)	20
Eructation	20/192 (10.4%)	22	10/102 (9.8%)	11
Heartburn/Dyspepsia	47/192 (24.5%)	57	15/102 (14.7%)	17
Nausea	32/192 (16.7%)	40	9/102 (8.8%)	9
Pain Abdominal	32/192 (16.7%)	38	19/102 (18.6%)	22
Emesis (vomiting)	20/192 (10.4%)	20	8/102 (7.8%)	10
Cramps abdominal	8/192 (4.2%)	8	6/102 (5.9%)	7
General disorders
Chest Pain	19/192 (9.9%)	19	2/102 (2%)	2
Skin reaction to coil/coil adhesion method	18/192 (9.4%)	21	8/102 (7.8%)	9
Energy decreased	14/192 (7.3%)	15	3/102 (2.9%)	3
Headache	20/192 (10.4%)	22	6/102 (5.9%)	7
Reaction to medicines	9/192 (4.7%)	10	5/102 (4.9%)	5
Metabolism and nutrition disorders
Out of range lab values	9/192 (4.7%)	9	3/102 (2.9%)	3
Vitamin or mineral insufficiency	14/192 (7.3%)	18	6/102 (5.9%)	8
Musculoskeletal and connective tissue disorders
Trauma	8/192 (4.2%)	11	9/102 (8.8%)	12
Psychiatric disorders
Depression	24/192 (12.5%)	24	6/102 (5.9%)	6
Anxiety	5/192 (2.6%)	7	5/102 (4.9%)	5
Renal and urinary disorders
Urinary tract infection	14/192 (7.3%)	15	9/102 (8.8%)	13
Respiratory, thoracic and mediastinal disorders
Cold/flu/respiratory tract infection	93/192 (48.4%)	170	46/102 (45.1%)	101
Skin and subcutaneous tissue disorders
Pain neuroregulator site	42/192 (21.9%)	47	28/102 (27.5%)	30
Wound redness or irritation	11/192 (5.7%)	12	4/102 (3.9%)	5
Paresthesia	4/192 (2.1%)	4	5/102 (4.9%)	5
Surgical and medical procedures
Incision pain incision site	7/192 (3.6%)	7	8/102 (7.8%)	8

Limitations/Caveats

Two confounding efficacy factors: Variable hours of therapy in both arms due to inconsistent external power source use and altered vagal excitability in the control arm due to small electrical inputs delivered to vagal nerves for safety checks.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.