Clinical trial NCT04276051: Cryovagotomy Diabetes Trial
Official title: Effects of Vagus Nerve Cryoablation on Glycemic Control and Weight Loss in Obese Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Type 2
Diabetes Mellitus
Obesity
Keywords: Obesity
Diabetes
Neurophysiology
Cryovagotomy
Glycemic control
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2020-02-19
Enrollment: 5
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Hemoglobin A1c
timeFrame: Baseline, Month 3, Month 6, Month 12
measure: Insulin Resistance Score Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, Month 3, Month 6, Month 12
measure: Number of Deaths Among Recipients of the Cryoablation
timeFrame: Up to Month 12
measure: Number of Adverse Events Related to the Cryoablation
timeFrame: Up to Month 12
Secondary outcomes:
measure: Body Mass Index (BMI)
timeFrame: Baseline, Month 3, Month 6
measure: Waist Circumference
timeFrame: Baseline, Month 3, Month 6
measure: Waist-to-hip Ratio
timeFrame: Baseline, Month 3, Month 6
measure: Total Cholesterol
timeFrame: Baseline, Month 6
measure: Low-Density Lipoprotein (LDL)
timeFrame: Baseline, Month 6
measure: Triglycerides
timeFrame: Baseline, Month 6
measure: Systolic Blood Pressure
timeFrame: Baseline, Month 3, Month 6
measure: Diastolic Blood Pressure
timeFrame: Baseline, Month 3, Month 6
measure: Daily Caloric Intake
timeFrame: Baseline, Month 3, Month 6
measure: Change in Anti-hyperglycemic Medication Regimen
timeFrame: Month 3, Month 6
measure: Appetite Visual Analog Scale Score for Hunger
timeFrame: Baseline, Week 1, Month 1, Month 3, Month 6
measure: Appetite Visual Analog Scale Score for Satisfaction
timeFrame: Baseline, Week 1, Month 1, Month 3, Month 6
measure: Appetite Visual Analog Scale Score for Fullness
timeFrame: Baseline, Week 1, Month 1, Month 3, Month 6
measure: Appetite Visual Analog Scale Score for Eating Quantity
timeFrame: Baseline, Week 1, Month 1, Month 3, Month 6
measure: Appetite Visual Analog Scale Score for Desire for Certain Foods
timeFrame: Baseline, Week 1, Month 1, Month 3, Month 6
measure: International Physical Activity Questionnaire (IPAQ) Score
timeFrame: Baseline, Month 3, Month 6
measure: Fasting Glucose Level
timeFrame: Baseline, Month 3, Month 6
measure: Fasting Insulin Level
timeFrame: Baseline, Month 3, Month 6
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Johns Creek
country: United States
facility: Emory Johns Creek Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Alexandra Migdal, MD
role: PRINCIPAL_INVESTIGATOR
References: