The global burden of diabetes, both type 1 (TIDM) and type 2 (T2DM), is increasing.
Gastroparesis is an under-recognized and significant complication of diabetes, whose lack
of effective treatment has severely handicapped diabetic management. Diabetic
gastroparesis (DG) can range up to half of T1DM patients in tertiary care. Recently, a
4-fold increase in hospitalizations has been seen in DG patients with refractory symptoms
despite medical therapy and inability to maintain oral nutrition - Grade 3 gastroparesis
or gastric failure. A critical barrier to progress has been both a lack of
pathophysiological understanding of DG and absence of effective treatments. A key
dysfunction in DG is felt to be diabetic autonomic neuropathy (DAN) that causes gastric
atony and segmental hypomotility of the small intestine, in addition to disruption of
urinary bladder function, sudomotor, pilomotor, and vasomotor activities. Autonomic
testing of DG patients in the NIDDK Gastroparesis Clinical Research Consortium (GpCRC)
showed sympathetic hypofunction was the only significant abnormality that distinguished
DG from diabetics with normal gastric emptying. The greater splanchnic nerve carries a
mix of sympathetic and parasympathetic nerve fibers in the abdomen6. Stimulation of the
thoracic dorsal roots or the greater splanchnic nerve in the thorax, pure sympathetic
stimulation, may enhance gastric contractility especially in states of gastric atony or
hypocontractility, as demonstrated in multiple animal studies.
Investigators have developed a novel, safe, noninvasive, and effective peripheral nerve
treatment, translumbosacral neuromodulation therapy (TNT), using repetitive magnetic
stimulation, for fecal incontinence (FI). In FI patients, investigators have demonstrated
that TNT can correct neuropathy and improve bowel function. The goal of this study is to
build on investigators' expertise to conduct a pilot, feasibility study by examining the
effect of Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT) in patients
with Grade 3 DG. Central hypothesis is that ThorS-MagNT will improve sympathetic
hypofunction, gastric hypomotility/atony, and spino-gut interactions and thereby improve
symptoms of DG. The impact of this work is to develop a safe, non-invasive
neuromodulation therapy for severe DG.
Specific Aim #1 - Evaluation of the Safety and Effectiveness of Thoracic Splanchnic
Magnetic Neuromodulation Therapy (ThorS-MagNT) in patients with Grade 3 Diabetic
Gastroparesis. To test the hypothesis that ThorS-MagNT will reduce symptoms of
gastroparesis, improve gastric emptying, and is well-tolerated. ThorS-MagNT is performed
by low-frequency, low-intensity repetitive magnetic stimulation bilaterally around T7-8
intravertebral space twice a day for 5 days with a total 1200 magnetic stimulations per
treatment session at 1 Hz. The primary outcome is responder rate, defined as ≥20%
reduction in the Gastroparesis Cardinal Symptom Index-daily diary (ANMS GCSI-DD) score.
Secondary outcomes include subscores of the ANMS GSCI-DD, effects on gastric emptying
time, Patient Global Impression of Improvement (PGI-I), safety, and tolerability.
Specific Aim #2 - Determination of predictive factors for response to ThorS-MagNT for
Diabetic Gastroparesis. To test the hypothesis that subjects with more severe disease as
assessed by the Patient Global Impression of Severity (PGI-S), poorly controlled
diabetes, increased Brain-derived neurotrophic factor (BDNF), and significant
neuroinflammation will predict better response to ThorS-MagNT.
Successful completion of this proposal will establish thoracic splanchnic neuromodulation
as a promising, safe, and non-invasive therapy for diabetic gastroparesis, a condition
sorely lacking in effective treatments, with potential to induce neuroplastic changes
along the spino-gastrointestinal pathway and result in a paradigm and conceptual shift in
current management of DG.