Participants
The study design and methods of the ReCharge Trial study have been described previously [3, 6]. The study participants were enrolled both in the USA (eight sites) and in Australia (two sites). BMI inclusion criteria were 35 to 40 kg/m2 with at least one obesity-related comorbidity (T2DM, hypertension, dyslipidemia, sleep apnea syndrome, or obesity related cardiomyopathy) or BMI of 40 to 45 kg/m2 with or without comorbidities. Prior to enrollment, the trial protocols were approved by the Institutional Review Boards at each site and informed consent was collected from all participants.
Study Design
The ReCharge Trial is a double-blind, randomized controlled trial comparing vBloc therapy delivered to the intra-abdominal vagal trunks via the Maestro Rechargeable System to a sham surgical procedure with the implantation of a sham device. The primary efficacy and safety outcomes were assessed at 12 months. Following the completion of all 12 month visits, participants were unblinded to their treatment assignment. Patients randomized to the Sham arm were given the option of crossing over to receive active vBloc therapy or withdrawing from the trial. Participants randomized to the vBloc arm continued to receive open-label vBloc therapy. Study design mandates that all participants in the ReCharge Trial are to be followed for a total of 5 years following implantation with an active vBloc device.
The safety of the study was monitored by an independent Data and Safety Monitoring Board, and all serious adverse events (SAEs) were independently adjudicated for relatedness by an independent clinical events committee (CEC). The study received institutional review board (IRB) or ethics committee (EC) approval from Bellberry Limited EC, Scottsdale Clinical Research Institute Scottsdale Healthcare, Tufts Medical Center IRB, Oregon Health & Science University IRB, Mayo Clinic Rochester IRB, Stanford University Medical Center IRB, University of Minnesota IRB, Scripps IRB, and Western IRB. The study was registered on clinicaltrials.gov with the identifier NCT01327976.
Intervention
The Maestro Rechargeable System consists of two leads placed around the anterior and posterior vagal trunks near the gastroesophageal junction using standard laparoscopic surgery and a rechargeable neuroregulator which is placed subcutaneously on the thoracic wall. The device is recharged transcutaneously [7]. Devices were programmed to 13 h of therapy per day to deliver at least 12 h of therapy daily since therapy cannot be delivered during recharging. The goal current amplitude was 6 mA. Investigators could adjust daily therapy duration and/or current amplitude based on weight loss and therapy tolerability. The average therapy delivery per day through 2 years was 11.5 ± 3.2 h at an average current amplitude of 5.9 ± 1 mA.
Monthly follow-up visits occurred between 12 and 24 months with a 2-week visit window. At each clinic follow-up visit, all participants were asked to participate in 15-min individual educational discussions on healthy food choices, exercise, and behavioral modification. Additionally, group weight management sessions were held approximately every 3 months. Of note, no new weight management material was provided in the second year of the trial; weight management advisors revisited topics at their discretion that had been discussed in the first year of the trial.
Study Objectives
The objective of the current report was to evaluate the impact of vBloc therapy on weight loss, obesity-related comorbid conditions, quality of life, and safety at 24 months. The Sham arm is no longer a valid comparator to the vBloc group at 2 years given the appreciable rate of either cross-over to an active vBloc device or withdrawal from the trial. Weight loss was assessed as %EWL using the BMI 25 kg/m2 method and %TWL. At every study visit, adverse events were collected using standard case report forms to capture the event type, investigator-attributed relatedness, seriousness, and severity.
Systolic and diastolic blood pressures were measured at baseline and at every visit. Blood pressure (in triplicate), laboratory parameters, and waist circumference were assessed at baseline and at yearly visits. The laboratory parameters of focus in this report were those known to be improved with significant weight loss: total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). The ReCharge Trial did not require that patients have elevated levels of these parameters to be eligible for enrollment, and many patients were well controlled on medications throughout the trial. However, a significant number of participants presented with abnormal metabolic and cardiovascular parameters, therefore, in addition to assessing change in these parameters among all participants, we also examined the change among participants with abnormal (i.e., elevated or low) levels of these parameters at baseline.
Quality of life (QOL) was assessed at baseline and every 6 months using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite), a validated QOL instrument with 31 questions that measures five domains: physical function, self-esteem, sexual life, public distress, and work [8]. Scores range from 0 to 100, with higher scores indicating better QOL. Changes in eating were evaluated using the Three-Factor Eating Questionnaire (TFEQ) at baseline and every 6 months. The TFEQ is a validated, self-report questionnaire that is used to measure the psychological constructs of eating on three subscales: cognitive restraint (0–21 scale), disinhibition (0–16 scale), and hunger (0–14 scale) [9].
Pre-Diabetes and Metabolic Syndrome Assessment
Exploratory assessments were done to determine if participants who presented with either pre-diabetes or metabolic syndrome at baseline still had the syndrome at 12 and 24 months. Pre-diabetes was defined according to the American Diabetes Association (ADA) diagnostic criteria for elevated FPG (≥100 to 125 mg/dL) and/or elevated HbA1c (≥5.7 and <6.5 %) for patients without diabetes and not on medications for endocrine disorders [10].
The metabolic syndrome definition used was taken from the National Cholesterol Education Program (NCEP) with the presence of three of the following conditions: elevated waist circumference (men >102 cm, women >88 cm), elevated triglycerides (≥150 mg/dL), low HDL (men <40 mg/dL, women <50 mg/dL), elevated blood pressure (≥130/85 mmHg or use of hypertension medications), and elevated FPG (≥110 mg/dL) [11].
Statistical Analysis
No statistical analysis plan was pre-specified for evaluation of changes after the 12-month primary assessment. For this report, the statistical significance of changes in weight and other continuous parameters in the vBloc group were evaluated using paired t tests comparing participants’ baseline values to their follow-up values. No statistical hypothesis tests were used for categorical parameters. All analyses are reported as complete case analyses without imputation or adjustment for multiple comparisons. P values less than 0.05 were considered statistically significant. All statistical analyses were performed using SAS version 9.3.