Clinical trial NCT04569721: Percutaneous CT-guided Cryoablation of the Splanchnic Nerves
Official title: Percutaneous CT-guided Cryoablation of the Splanchnic Nerves for the Management of Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Type 2 Diabetes
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Georgia Research Alliance
First posted: 2020-09-30
Enrollment: 0
Sex: ALL
Minimum age (years): 22
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of freezing (cryoablation) of the splanchnic nerve for management of diabetes. The splanchnic nerves carry signals from the brain to help regulate the way organs function. Quieting these signals, by freezing the splanchnic nerves, may help the body regulate blood sugar. The study procedure will take about 30 minutes and the researchers hope that it will help people to control their blood sugars, lose weight, and possibly improve blood pressure.

Detailed description: Type 2 diabetes (T2D) is a disease of pandemic proportion, affecting approximately 425 million adults worldwide. The incidence of T2D is increasing in most countries and it is predicted that by the year 2045, 629 million adults will be diagnosed with T2D worldwide. Chronically elevated sympathetic activity has been shown to contribute to the development of metabolic syndrome and T2D. Overweight/obese individuals demonstrate elevated noradrenaline and metabolite levels relative to lean healthy individuals - this is particularly concerning since long term prospective studies have shown that noradrenaline levels predict future risk of T2D. Furthermore, dysfunctional sympathetic response to glucose loads is demonstrated amongst those with T2D compared to pre-diabetes. Since the greater splanchnic nerve is the main source of sympathetic input to the viscera, the researchers postulate that denervation of the splanchnic nerve would lead to decreased sympathetic tone, thereby improving glycemic control in patients with T2D. To the researchers' knowledge, this would be the first study to evaluate the role of splanchnic cryoablation as a potential therapeutic for T2D and insulin resistance.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Type 2 diabetes mellitus (T2DM) for \<10 years
* HbA1c between ≥7.5% and ≤10.5%
* Willing to comply with study requirements
* Subjects have failed lifestyle interventions as a first line treatment
* Body mass index (BMI) between 30 and 37

Exclusion Criteria:

* Diagnosis of type 1 diabetes or history of diabetic ketoacidosis
* Thyroid disease unless on stable medications for \>3 months
* Systemic steroid use within 30 days
* Use of prescription or over the counter weight loss medications within 6 months prior to randomization
* Any condition or major illness that places the subject at undue risk by participating in the study
* Psychiatric condition rendering the subject unable to understand the possible consequences of the study
* Inability to provide informed consent
* Positive pregnancy test at time of cryoablation procedure
* 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
* 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
* Active or recent infection
* Immunosuppression
* 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)
* History of autonomic dysfunction, including amyloidosis, Parkinson's disease, autoimmune disease, spinal cord injury
* History of heart failure
* History of macro-occlusive vascular disease
* Glomerular filtration rate (GFR) \< 60 mL/min/1.73 m2
* History of abnormal pulmonary function or pulmonary intervention (e.g., thoracotomy, thoracentesis, pneumothorax, or thoracic trauma)
* History of or current substance abuse
* Weight gain or loss of \>5% during the six months preceding enrollment
* Use of any antihyperglycemic agents aside from metformin or sulfonylurea therapy

Primary outcomes:
measure: Mortality
timeFrame: Month 12
measure: Number of Procedure Related Complications
timeFrame: Month 12
Secondary outcomes:
measure: Change in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Fasting Glucose
timeFrame: Baseline, Day 7, Months 1, 3, 6, and 12
measure: Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Body Weight
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Waist Circumference
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Waist-to-Hip Ratio
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Total Cholesterol
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Low-Density Lipoprotein (LDL)
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in High-Density Lipoproteins (HDL)
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Triglyceride Levels
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Systolic Blood Pressure
timeFrame: Baseline, Day 7, Months 1, 3, 6, and 12
measure: Change in Diastolic Blood Pressure
timeFrame: Baseline, Day 7, Months 1, 3, 6, and 12
measure: Change in Orthostatic Blood Pressure
timeFrame: Baseline, Day 7, Months 1, 3, 6, and 12
measure: Change in Serum Catecholamine Measurements
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Glucose Tolerance
timeFrame: Baseline, Months 1, 3, 6, and 12
measure: Change in Fasting Insulin Levels
timeFrame: Baseline, Day 7, Months 1, 3, 6, and 12
measure: Change in Fasting C-peptide Levels
timeFrame: Baseline, Day 7, Months 1, 3, 6, and 12
Other outcomes:
Locations:
city: Johns Creek
country: United States
facility: Emory Johns Creek Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: John D Prologo, MD
role: PRINCIPAL_INVESTIGATOR
References: