ELIRA 2: Safety and Effectiveness of TENS Assisted Weight Loss and Appetite Suppression

Study Overview
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Brief Summary
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The objectives of this study are to demonstrate safety and effectiveness of a wearable patch TENS system (Appendix 2) in driving weight loss and appetite suppression when coupled with an integrated weight loss reduction strategy. The study is designed to demonstrate that TENS stimulation sufficient to drive weight loss and appetite suppression is safe and tolerable when compared to standard of care, and that adverse events/adverse device effects are similar to other TENS device use cases.

Detailed Description
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Randomized, adaptive parallel arm study. Subjects will be initially screened during a screening period (+/- 7 days). During this screening period, subjects will sign an Informed Consent Form (ICF), have their weight/height and blood pressure measured as part of a physical exam, take a pregnancy test (females of child bearing potential), get blood drawn for analysis (blood lipids, HbA1c), and complete the PHQ-9 and pre-study survey. At the end of the screening period, eligible subjects will be enrolled/randomized in the study and be randomized to either a treatment or control group. After enrolling, both control and treatment subjects will be instructed to follow a healthy diet and reduce calories as desired for the duration of the study and will receive training on the use of the electronic scale and completion of paper diaries. For the treatment group, subjects will be instructed on use of the Elira wearable patch system. Photographs will be taken at the enrollment visit. Following this, subjects will enter the Therapy Period for  24-weeks. At the 12 week visit, subjects will be assessed for weight loss, blood pressure, blood lipids, HbA1c, patient preference questionnaire and their participation will continue through months 4-6 for the Safety phase of the Therapy Period. The Therapy Period will be considered complete (pending laboratory results, adverse events or serious adverse events). Patient (treatment) photographs will also be taken at the 12 week visit. The study utilizes an adaptive approach where cohorts of enrolled/randomized subjects (in groups of  25 per arm) are assessed for dose response and progression to achievement of primary and secondary endpoints. Frequent interim endpoint assessment utilizing Markov-chain Monte Carlo (MCMC) methods coupled with Longitudinal analyses will be utilized to determine sample sizes for future cohorts (assessed primarily via Normal dynamic linear modeling [NDLM]). Long term safety of the device will be shown through 6 months of usage.

Official Title
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Safety and Effectiveness of Transcutaneous Electrical Nerve Stimulation (TENS)-Assisted Weight Loss and/or Appetite Suppression

Conditions
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Weight Loss

Intervention / Treatment
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* Device: Transcutaneous Nerve Stimulator (TENS)
* Behavioral: Diet & Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is between 18 - 65 years of age inclusive. Subject has a BMI of 25-35 kg/ m2 inclusive. Subject has signed the informed consent form and is able to comply with study protocol and adhere to study visit schedule. Subject is able to wear and use a wearable, patch TENS system. Subject is able to use a touch screen hand held smart phone. Subject is fluent in English and can complete questionnaires. Females of childbearing potential (FOCBP) must have a negative urine pregnancy test at screening or enrollment visit, prior to placement of ELIRA device. Subject is male or non-pregnant, non-lactating female, who agrees to use effective contraceptive methods throughout the length of the trial based on PI approval. Exclusion Criteria: Subject has any known gastrointestinal disorder that in the opinion of the PI precludes enrollment into the trial. Subject has had a prior bariatric procedure or any previous procedure on the stomach. Subject has any significant multisystem disease in the opinion of the PI. Subject has > 6.5 HbA1c. Subject has significant cardiac arrhythmia, ectopy, or significant cardiovascular disease. Subject has an existing implanted electrical stimulator (e.g., pacemaker, AICD). Subject is a female of child-bearing potential who is pregnant or intends to become pregnant during the trial period. Subject has current and/or a history of cancer within the past 5 years (not including basal cell carcinoma or cervical carcinoma in situ). Subject has had a weight change of + 5% of his/her Total Body Weight in the 3 months prior to screening. Subject has a moderate / severe psychiatric disorder. Subject has a diagnosed neurological disease. Subject has a diagnosed eating disorder. Subject has a skin disorder affecting the thoracic dermatomes. Subject has active or /has ever had shingles in the abdominal area. Subject has abdominal surgery or other scars which may interfere with TENS stimulation in the opinion of the PI. Subject is currently enrolled in other potentially confounding research. Subject has known allergic reaction to materials in the TENS electrodes and/or is otherwise unable to tolerate stimulation with the wearable TENS system. This includes known allergies to latex, nickel and/or hydrogels. Subject has a history of sensitive skin, including eczema wheel-and-flare or other skin irritation, per PI discretion. Subject is actively participating or unwilling to discontinue participation in another weight loss program. Subjects may not enroll in paid or unpaid programs that involve in-person or online apps or coaching, beginning new fitness regimens or utilizing meal planning or paid nutritional coaching during the course of the ELIRA study Subject is taking weight loss control medications including but not limited to Over The Counter (OTC) medications, Metformin, and Belviq. (See Appendix 8) Subject is planning any major medical treatments or surgeries that could cause weight loss. Subject is unable to take anti-nausea medications planned for the study. Inability to walk at least 0.8 kilometers per day (10 minutes of continuous walking). Current smoker or user of nicotine product or smoking cessation within 1 year of the screening date. History of treatment for or current abuse of drug or alcohol. A score of ≥10 on the Patient Health Questionnaire 9 (PHQ-9), demonstrating moderate depression. Any subject that the investigator considers inappropriate for the study for medical reasons. Subject has a history of moderate/severe migraines or other severe headache disorders requiring the treatment of Topiramate. Subject is on drug therapy which may alter antral motility or appetite, per PI discretion.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, adaptive parallel arm study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>The Transcutaneous Nerve Stimulator (TENS) Elira wearable patch system will be applied to varying locations on the T6/T7 dermatome for 30 minutes three times a day after meals. Subjects will be instructed to follow a 1200 calorie healthy diet and record any changes in appetite. | Device: Transcutaneous Nerve Stimulator (TENS)<br>* The Elira wearable patch system is a Radio Frequency (RF) coupled, wearable transcutaneous electrical nerve stimulator (TENS) device controlled via Bluetooth by a smart phone unit running a custom application which directs therapy from the patch within safe limits set by a clinician and also includes a weight loss diary. Behavioral: Diet & Exercise Subjects to be instructed on a healthy 1200 calorie diet.<br>Behavioral: Diet & Exercise<br>* Subjects to be instructed on a healthy 1200 calorie diet.<br>|
| Active Comparator: Control<br>Open label diet and exercise counseling only. Subjects will be instructed to follow a healthy 1200 calorie diet and record any changes in appetite. | Behavioral: Diet & Exercise<br>* Subjects to be instructed on a healthy 1200 calorie diet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events | Treatment Emergent Adverse Events [Time Frame: 12 weeks] Safety/Tolerability will be assessed by the non-inferiority of incidence of serious adverse events (SAEs), unanticipated serious adverse events (USAEs), device-related SAEs (DSAEs), and unanticipated device-related SAEs (UDAEs) that are associated with the TENS therapy throughout the stimulation and the follow-up period versus historical control (compared with other TENS systems). | 12 weeks | 
| Change in Appetite as Measured by a Visual Analogue Scale From Baseline | Appetite Changes [Time Frame: 12 weeks] Percent change in appetite scores at the end of the trial compared to Baseline between Treatment and Control. Subjects are asked to score level of satisfaction, fullness, hunger and ability to eat on a Visual Analogue Scale of 1 to 100 before and after meals with lower scores indicating lower satisfaction, fullness, hunger or ability to eat, respectively. Scores are captured in a diary once a week with 8 time points. The weeks are captured as week 0 through week 12. The time points at each week include: 30 minutes before breakfast 30, 60, and 90 minutes after breakfast Pre-lunch Midafternoon 30 minutes before dinner Bedtime For each of the four appetite suppression variables (satisfaction, fullness, hunger and ability to eat), the 8 time points at week zero will be averaged for the baseline score (baseline), and the 8 time points at week 12 will be averaged for the 3-month score (3month). | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percent Total Body Weight Loss | Percent reduction in total body weight loss (%TBWL), measured as End Weight - Initial Weight, multiplied by 100, at the end of Experimental period compared to Baseline between Treatment and Control. | 3 months | 
| Changes in BMI | Changes in BMI [ Time Frame: 3 months ] | 3 months |