# Diabetic Targeted Dual Neuromodulation Parametric Optimization

> **NIH NIH R43** · RESHAPE LIFESCIENCES, INC. · 2024 · $345,650

## Abstract

Project Summary/Abstract
31 million Americans suffer from Type 2 Diabetes Mellitus (T2DM) with numbers growing in the elderly and
children. Also, 84.1 million prediabetic Americans risk becoming diabetic. Current pharmaceutical therapies
are expensive and have negative side-effects with poor patient compliance. Bariatric surgery provides a high
initial complete, or partial T2DM remission. However, these procedures are complex, prone to potentially
harmful side-effects, treatment durability is questionable and typically indicated only for morbidly obese
patients unresponsive to pharmaceutical therapy. We propose Diabetes Targeted Dual Neuromodulation
Therapy (TDN Therapy), an innovative approach to blood glucose reduction. TDN implantable pulse
generators (IPGs) block conduction of the hepatic branch of the Vagus nerve w/ High Frequency Alternating
Current (HFAC) while stimulating the celiac branch. This SBIR Phase I study will successfully demonstrate
feasibility of TDN Therapy for treatment of T2DM by validation of our hypothesis that decreased TDN
HFAC signal amplitude will maintain glycemic control. Specific Aim 1: We have demonstrated that a TDN
HFAC amplitude of 8 mA increases glycemic control in alloxan treated swine. However, the minimum current
amplitude for effective TDN is unknown. A safe and efficient commercialized TDN device depends heavily on
an optimal HFAC current amplitude. We propose testing HFAC TDN amplitudes below 8 mA in alloxan treated
swine during oral glucose tolerance tests (OGTTs). Feasibility: Demonstrated by determining if lower HFAC
amplitudes than 8 mA can maintain TDN efficacy. Aim 2: Low HFA current amplitudes are advantageous to
decrease off-target effects as well as increase device efficacy. Feasibility: Demonstrated by preservation of
euglycemia with downward HFAC titration. Aim 3: Autonomic function changes precede T2DM development
and are resolved following effective treatment. Heart rate variability (HRV) is a surrogate for vagal tone. Lower
HRV precedes cardiovascular T2DM co-morbidities and has been observed in diabetic swine. Feasibility:
Demonstrated by increasing HRV with TDN during Aim 1 and Aim 2 experiments. Aim 4: Patients report
esophageal sensations and heart burn when receiving monopolar HFAC delivered to the abdominal vagal
trunks. This is presumably due to stray current exciting esophageal smooth muscle. Feasibility:
Demonstrated by determining thresholds of TDN induced esophageal contractions & heart rate changes.
Demonstrating minimal to no acute cardiovascular effects would set TDN apart from all other VNS approaches
and give TDN commercial advantages. We envision the future commercial TDN device with Bluetooth
capabilities allowing patients device/therapy interaction through smart devices with a possible closed-loop
system to work with non-calibrating continuous glucose monitors and therapy refinement with the use of AI
and machine learning.

## Key facts

- **NIH application ID:** 10920167
- **Project number:** 1R43DK137628-01A1
- **Recipient organization:** RESHAPE LIFESCIENCES, INC.
- **Principal Investigator:** JON James WAATAJA
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $345,650
- **Award type:** 1
- **Project period:** 2024-08-20 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920167

## Citation

> US National Institutes of Health, RePORTER application 10920167, Diabetic Targeted Dual Neuromodulation Parametric Optimization (1R43DK137628-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10920167. Licensed CC0.

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