Cryovagotomy Diabetes Trial

NCT ID: NCT04276051

Last Updated: 2023-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-23
• Study Completion Date: 2022-02-08

Brief Summary

The pilot study will assess the feasibility and efficacy of cryoablation procedure to freeze the vagus nerve in obese patients with type 2 diabetes. Aim 1 will focus on changes in glycemic control. Aim 2 will evaluate differences in body weight and anthropometric measurements. This study will provide much needed data for a novel therapeutic intervention to manage obese patients with type 2 diabetes.

Detailed Description

Obesity is a growing epidemic, currently affecting over 1/3 of the adult US population and is a well-established risk factor for the development of diabetes and cardiovascular disease. Given that the majority of patients with type 2 diabetes (T2D) are obese, weight loss is the cornerstone of treatment, and has been shown to decrease risk of long term complications, lead to improvements in A1c and lipid levels, as well as decreased need for medications and improvements in quality of life. Unfortunately, lifestyle intervention is often ineffective at achieving long-term sustainable, clinically significant weight loss. Bariatric surgery is a successful intervention, leading to 20-30% weight loss with remission of diabetes in 30-65% of patients 1-5 years post surgery. However, this invasive procedure is associated with high rates of short- and long-term complications, including need for reoperations, vitamin/mineral deficiencies, anemia, and osteoporosis. It is clear that the current management options for obese patients, including lifestyle changes, medications and surgery, are suboptimal and innovative strategies are necessary to optimize diabetes control and weight management.

Energy balance and glycemic control are mediated largely by the gut-brain axis, specifically the vagus nerve. The vagus nerve can stimulate or inhibit food intake depending on nutritional status. Vagal nerve signaling is disrupted in the setting of obesity and thought to contribute to overeating behaviors. Vagus nerve blockade has the potential to be a highly efficacious, minimally invasive intervention to address current obesity treatment limitations. Clinical studies evaluating the efficacy of an implantable electric vagus nerve blockade device found that subjects lost on average 8.8% of total body weight at 1 year; patients with T2D experienced improved glycemic control, with an average A1c improvement of 1.0% at 12 months. Unfortunately, nearly 40% of subjects experienced side effects related to the device. A recent pilot study from the researchers of this study reported weight loss efficacy of a minimally invasive computerized tomography (CT) guided cryoablation of the vagus nerve in obese, non-diabetic subjects. Patients lost 5.6% of total body weight and 22.7% excess body weight at 6 months with no significant side effects. The purpose of this current study is to evaluate the feasibility and efficacy of this procedure through a randomized control trial in obese patients with T2D. The researchers hypothesize that those patients undergoing the cryoablation procedure will experience improvement in glycemic control and enhanced weight loss at 6 months follow-up compared to the control group.

Participants will be randomized to receive either CT guided cryoablation of the vagus nerve plus lifestyle intervention or lifestyle intervention alone. The lifestyle intervention lasts for 26 weeks and participants will be followed for 12 months in total.

Conditions

Diabetes Type 2; Diabetes Mellitus; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cryoablation of the Vagus Nerve Plus Lifestyle Intervention

Participants randomized to receive cryoablation of the vagus nerve as well as standardized dietary and exercise counseling from a registered dietitian and exercise physiologist.

Group Type: EXPERIMENTAL

Cryoablation of the Vagus Nerve

Intervention Type: DEVICE

The Visual ICE Cryoablation System is a mobile console system intended for cryoablative tissue destruction using a minimally invasive procedure. The Visual-ICE System uses high-pressure argon gas that circulates through closed-tip cryoablation needles to induce tissue freezing. Active tissue thawing is achieved by circulating helium gas through the needles or, alternatively, by the use of Galil Medical i-Thaw technology. The procedure will be done under CT guidance and involves a 4-5 mm scalpel incision followed by percutaneous probe placement about the posterior gastroesophageal junction (the location of the posterior vagal trunk). The probe will create a zone of decreased temperature (-20 to -40 degrees Celsius) involving the posterior vagal nerve fibers/plexus. The cryoablation process will include a 3-minute freeze, followed by a 1-minute thaw, and a second 3-minute freeze and 1 minute thaw.

Lifestyle Intervention

Intervention Type: BEHAVIORAL

The lifestyle intervention structure will include three face-to-face counseling sessions at baseline, 3 and 6 months. Dietary counseling to follow a low carbohydrate diet will be provided by a registered dietitian. Focus will be on increasing fruits and vegetables and decreasing refined sugars and processed foods. It will also include motivational interviewing, goal setting and nutrition education. In addition, subjects will be encouraged by exercise physiologist to slowly increase physical activity to at least 150 minutes weekly. There will be weekly phone calls or texts (participants' choice) providing a total of 26 points of contact recommended by the United States Preventive Services Task Force.

Lifestyle Intervention Only

Participants randomized to receive standardized dietary and exercise counseling from a registered dietitian and exercise physiologist.

Group Type: ACTIVE_COMPARATOR

Lifestyle Intervention

Intervention Type: BEHAVIORAL

The lifestyle intervention structure will include three face-to-face counseling sessions at baseline, 3 and 6 months. Dietary counseling to follow a low carbohydrate diet will be provided by a registered dietitian. Focus will be on increasing fruits and vegetables and decreasing refined sugars and processed foods. It will also include motivational interviewing, goal setting and nutrition education. In addition, subjects will be encouraged by exercise physiologist to slowly increase physical activity to at least 150 minutes weekly. There will be weekly phone calls or texts (participants' choice) providing a total of 26 points of contact recommended by the United States Preventive Services Task Force.

Interventions

Cryoablation of the Vagus Nerve

The Visual ICE Cryoablation System is a mobile console system intended for cryoablative tissue destruction using a minimally invasive procedure. The Visual-ICE System uses high-pressure argon gas that circulates through closed-tip cryoablation needles to induce tissue freezing. Active tissue thawing is achieved by circulating helium gas through the needles or, alternatively, by the use of Galil Medical i-Thaw technology. The procedure will be done under CT guidance and involves a 4-5 mm scalpel incision followed by percutaneous probe placement about the posterior gastroesophageal junction (the location of the posterior vagal trunk). The probe will create a zone of decreased temperature (-20 to -40 degrees Celsius) involving the posterior vagal nerve fibers/plexus. The cryoablation process will include a 3-minute freeze, followed by a 1-minute thaw, and a second 3-minute freeze and 1 minute thaw.

Intervention Type: DEVICE

Lifestyle Intervention

The lifestyle intervention structure will include three face-to-face counseling sessions at baseline, 3 and 6 months. Dietary counseling to follow a low carbohydrate diet will be provided by a registered dietitian. Focus will be on increasing fruits and vegetables and decreasing refined sugars and processed foods. It will also include motivational interviewing, goal setting and nutrition education. In addition, subjects will be encouraged by exercise physiologist to slowly increase physical activity to at least 150 minutes weekly. There will be weekly phone calls or texts (participants' choice) providing a total of 26 points of contact recommended by the United States Preventive Services Task Force.

Intervention Type: BEHAVIORAL

Other Intervention Names

Visual ICE Cryoablation System

Eligibility Criteria

Inclusion Criteria

1. Males and females between the ages of 22-65

2. Diagnosis of type 2 diabetes mellitus (T2DM) for <10 years

3. HbA1c between ≥7.5% and ≤10.5%

4. Treatment with non-insulin antidiabetic medications with stable doses for at least 3 months, with failed prior attempts at dietary interventions to optimize diabetes control

5. BMI 30-40 kg/m^2

6. Willing to comply with study requirements

7. Documented negative pregnancy test in women of child bearing potential and use of an effective birth control method

8. Average score of ≥3 on questions 4, 8, 9, 13, and 14 from the Three Factor Eating Questionnaire

Exclusion Criteria

1. Diagnosis of type 1 diabetes or history of diabetic ketoacidosis

2. Use of insulin therapy

3. Significant kidney disease (eGFR < 60 ml/min/1.73m^2)

4. Current drug or alcohol addiction

5. Thyroid disease unless underlying diagnosis is primary hypothyroidism on stable medications for >3 months with thyroid stimulating hormone (TSH) in reference range at time of screening visit

6. Systemic steroid use within 30 days prior to randomization

7. Use of prescription or over the counter weight loss medications within 6 months prior to randomization

8. Weight gain/loss >5% over the past 6 months

9. Previous GI surgery or abnormal GI anatomy which may limit technical feasibility of the procedure

10. Recent diagnosis of cardiovascular disease requiring percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) within the past 6 months

11. Abnormal pathologies or conditions of the GI tract, including peptic ulcers, hiatal hernia, active gallbladder disease, pancreatitis, cirrhosis, inflammatory bowel disease, upper GI bleed within 6 months of randomization

12. Any condition or major illness that places the subject at undue risk by participating in the study

13. Psychiatric condition rendering the subject unable to understand the possible consequences of the study

14. Inability to provide informed consent

15. Female subjects who have been pregnant within 6 months or breast-feeding at time of enrollment into the study, or women who plan to become pregnant within the next 12 months

16. Diagnosis of anemia, red blood cell (RBC) transfusion in the preceding 3 months or expectation to receive transfusion within the next 12 months, or hemoglobinopathies that would affect HbA1c reliability

17. Active or recent infection

18. Immunosuppression

19. History of coagulopathy or high risk for development of deep vein thrombosis (including congestive heart failure, those who are non-ambulatory, active leukemia/lymphoma, prior thrombotic events, family history of thrombosis)

20. History of blood pressure instability (systolic BP ≤100 or ≥160 mmHg)

21. History of autonomic dysfunction, including amyloidosis, Parkinson's disease, autoimmune disease, spinal cord injury

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Alexandra Migdal

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alexandra Migdal, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Grady Health System

Atlanta, Georgia, United States

The Emory Clinic

Atlanta, Georgia, United States

Emory Johns Creek Hospital

Johns Creek, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00109624

Identifier Type: -

Identifier Source: org_study_id