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Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT) for Grade 3 Diabetic Gastroparesis: Pilot Study (ThorS-MagNT)

Primary Purpose

Diabetic Gastroparesis

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Thoracic Splanchnic Magnetic Neuromodulation Therapy
Sponsored by
Augusta University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Gastroparesis

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Previously diagnosed diabetic gastroparesis patients admitted with persistent symptoms after correction of metabolic disturbance;
  2. Men or women age less than 85;
  3. No known mucosal disease

Exclusion Criteria:

  1. Postsurgical gastroparesis;
  2. Gastrointestinal obstruction or presence of gastric bezoar;
  3. Prior gastric surgery (fundoplication, gastric resection or pyloroplasty);
  4. Active inflammatory bowel disease;
  5. Eosinophilic gastroenteritis;
  6. Connective tissue disease;
  7. Chronic liver disease;
  8. Use of opioids, tricyclic antidepressants;
  9. Active depression;
  10. Severe cardiac disease and arrhythmias;
  11. Metal implants, including gastric electrical stimulators (GES) deep brain stimulators (DBS), sacral nerve stimulators (SNS), or pacemakers;
  12. Pregnant women or nursing mothers.

Sites / Locations

  • Augusta UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

ThorS-MagNT Treatment

Arm Description

Low-frequency, low-intensity repetitive magnetic stimulation bilaterally at T7-8 intravertebral space twice a day for 5 days with a total 1200 magnetic stimulations per treatment session at 1 Hz.

Outcomes

Primary Outcome Measures

Responder rate
The responder rate is defined as an improvement in the Gastroparesis Cardinal Symptom Index-daily diary (ANMS GCSI-DD) score (e.g., >20% decrease in total symptom score from baseline) in at least 50% of the days of treatment.

Secondary Outcome Measures

Sub-scores of the ANMS GSCI-DD
The change in 1. severity of nausea, 2. severity of early satiety, 3. severity of postprandial fullness, 4. severity of upper abdominal pain, 5. number of vomiting episodes, and 6. severity of gastroparesis during 5 days of ThorS-MagNT treatment.
Gastric emptying time
The change in gastric emptying time after 5 days of ThorS-MagNT treatment and 14 days after treatment.
Patient Global Impression of Improvement (PGI-I)
The change in Patient Global Impression of Improvement (PGI-I) score after 5 days of ThorS-MagNT treatment and 14 days after treatment.

Full Information

First Posted
January 11, 2021
Last Updated
January 25, 2021
Sponsor
Augusta University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT04706832
Brief Title
Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT) for Grade 3 Diabetic Gastroparesis: Pilot Study
Acronym
ThorS-MagNT
Official Title
Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT) for Grade 3 Diabetic Gastroparesis: Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 5, 2020 (Actual)
Primary Completion Date
June 30, 2021 (Anticipated)
Study Completion Date
September 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Augusta University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes

5. Study Description

Brief Summary
Diabetic gastroparesis (DG) is an under recognized and significant complication of diabetes with lack of effective treatments. Recently, a 4-fold increase in hospitalizations has been seen in DG patients with refractory symptoms, defined as Grade 3 gastroparesis. A critical barrier to progress has been both a lack of pathophysiological understanding of DG and absence of effective treatments. Diabetic autonomic neuropathy is felt to be a key dysfunction in DG that causes gastric atony and segmental hypomotility of the small intestine. Autonomic testing of DG patients reveals significant sympathetic hypofunction, a feature distinguishing DG from diabetics with normal gastric emptying. Therefore, stimulation of the thoracic dorsal roots of the greater splanchnic nerve (sympathetic stimulation) could enhance gastric motility, as observed in animal models, and improve DG. Investigators have developed a novel, safe, noninvasive peripheral nerve treatment using repetitive magnetic stimulation, and have demonstrated improvement in fecal incontinence with neuropathy. The goal of this study is to build on our 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. The aims are to evaluate the safety, effectiveness and feasibility of ThorS-MagNT in patients with Grade 3 DG and to evaluate predictive factors of treatment. The central hypothesis is that ThorS-MagNT will improve sympathetic hypofunction, gastric motility, and spino-gut interactions, and thereby, improve symptoms of DG. ThorS-MagNT will be performed in 12 patients hospitalized with severe DG by using low-frequency, low-intensity repetitive magnetic stimulation, bilaterally, around T7 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. The impact of this work is to develop a novel, safe, and non-invasive treatment for severe DG that could result in a paradigm shift in management of DG.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Gastroparesis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ThorS-MagNT Treatment
Arm Type
Other
Arm Description
Low-frequency, low-intensity repetitive magnetic stimulation bilaterally at T7-8 intravertebral space twice a day for 5 days with a total 1200 magnetic stimulations per treatment session at 1 Hz.
Intervention Type
Device
Intervention Name(s)
Thoracic Splanchnic Magnetic Neuromodulation Therapy
Other Intervention Name(s)
ThorS-MagNT
Intervention Description
ThorS-MagNT is performed by low-frequency, low-intensity repetitive magnetic stimulation bilaterally around T7-8 intervertebral space twice a day for 5 days with a total 1200 magnetic stimulations per treatment session at 1 Hz.
Primary Outcome Measure Information:
Title
Responder rate
Description
The responder rate is defined as an improvement in the Gastroparesis Cardinal Symptom Index-daily diary (ANMS GCSI-DD) score (e.g., >20% decrease in total symptom score from baseline) in at least 50% of the days of treatment.
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Sub-scores of the ANMS GSCI-DD
Description
The change in 1. severity of nausea, 2. severity of early satiety, 3. severity of postprandial fullness, 4. severity of upper abdominal pain, 5. number of vomiting episodes, and 6. severity of gastroparesis during 5 days of ThorS-MagNT treatment.
Time Frame
1 week
Title
Gastric emptying time
Description
The change in gastric emptying time after 5 days of ThorS-MagNT treatment and 14 days after treatment.
Time Frame
3 weeks
Title
Patient Global Impression of Improvement (PGI-I)
Description
The change in Patient Global Impression of Improvement (PGI-I) score after 5 days of ThorS-MagNT treatment and 14 days after treatment.
Time Frame
3 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Previously diagnosed diabetic gastroparesis patients admitted with persistent symptoms after correction of metabolic disturbance; Men or women age less than 85; No known mucosal disease Exclusion Criteria: Postsurgical gastroparesis; Gastrointestinal obstruction or presence of gastric bezoar; Prior gastric surgery (fundoplication, gastric resection or pyloroplasty); Active inflammatory bowel disease; Eosinophilic gastroenteritis; Connective tissue disease; Chronic liver disease; Use of opioids, tricyclic antidepressants; Active depression; Severe cardiac disease and arrhythmias; Metal implants, including gastric electrical stimulators (GES) deep brain stimulators (DBS), sacral nerve stimulators (SNS), or pacemakers; Pregnant women or nursing mothers.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amol Sharma, MD, MS
Phone
706-446-5848
Email
amosharma@augusta.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tennekoon B Karunaratne, MD, PhD
Phone
706-721-1968
Email
tkarunaratne@augusta.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amol Sharma, MD, MS
Organizational Affiliation
Augusta University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amol Sharma, MD, MS
Phone
706-446-5848
Email
amosharma@augusta.edu
First Name & Middle Initial & Last Name & Degree
Tennekoon B Karunaratne, MD,PhD
Phone
706-721-1968
Email
tkarunaratne@augusta.edu
First Name & Middle Initial & Last Name & Degree
Tennekoon B Karunaratne, MD, PhD
First Name & Middle Initial & Last Name & Degree
Deepak N Ayyala, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Thoracic Splanchnic Magnetic Neuromodulation Therapy (ThorS-MagNT) for Grade 3 Diabetic Gastroparesis: Pilot Study

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