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Percutaneous CT-guided Cryoablation of the Splanchnic Nerves

Primary Purpose

Type 2 Diabetes

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

CT Guided Splanchnic Cryoablation

About this trial

This is an interventional device feasibility trial for Type 2 Diabetes

Eligibility Criteria

22 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Emory Johns Creek Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CT guided splanchnic cryoablation

Arm Description

Obese patients with type 2 diabetes receiving CT guided splanchnic cryoablation.

Outcomes

Primary Outcome Measures

Mortality

The number of participant deaths will be used to assess the safety of the study procedure.

Number of Procedure Related Complications

Safety will be assessed by examining procedure related complications, such as bleeding, infection, hypotension, pain, cardiac abnormalities, gastrointestinal abnormalities, or endocrine abnormalities.

Secondary Outcome Measures

Change in Hemoglobin A1c (HbA1c)

HbA1c is a measurement of a persons average blood sugar levels over the prior 3 months. A normal value is below 5.7%. Prediabetes is indicated for levels between 5.7% and 6.4%. Diabetes is diagnosed for values of 6.5% and above.

Change in Fasting Glucose

Fasting plasma glucose measures glucose levels after one has fasted for at least 8 hours. Normal values are below 100 mg/dl. Prediabetes is indicated with values between 100 mg/dl and 125 mg/dl. Diabetes is diagnosed when values are at 126 mg/dl and greater.

Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

HOMA-IR is a measure of insulin resistance and is calculated as insulin (uIU/mL) times glucose (mg/dL), divided by 405. Values under 1.0 indicate optimal insulin sensitivity. Values greater than 1.9 indicate early insulin resistance while values over 2.9 indicate significant insulin resistance.

Change in Body Weight

Body weight will be measured in kilograms (kg).

Change in Waist Circumference

Waist circumference will be measured in centimeters (cm).

Change in Waist-to-Hip Ratio

The waist-to-hip ratio is calculated as waist circumference (cm) divided by hip circumference (cm). A healthy ratio for women is 0.85 or less and a healthy ratio for men is 0.9 or less. Ratios of 1.0 and greater are associated with increased risk for illnesses that are associated with being overweight.

Change in Total Cholesterol

Measuring cholesterol is a diagnostic tool used for estimating risk of cardiac disease. Total cholesterol levels below 200 mg/dL are considered normal.

Change in Low-Density Lipoprotein (LDL)

High levels of LDL leads to arteriosclerosis. LDL levels below 100 mg/dL are considered optimal, however, persons with diabetes or cardiac disease are advised to keep levels below 70 mg/dL.

Change in High-Density Lipoproteins (HDL)

HDL values between 40 and 59 mg/dL are considered normal. HDL values under 40 mg/dL are associated with increased risk of developing heart disease and stroke.

Change in Triglyceride Levels

Triglycerides levels measure fat in blood and high triglyceride levels are associated with health concerns such as high blood pressure and diabetes. Normal levels are below 150 mg/dL, borderline high levels are between 150 and 199 mg/dL, and high levels of triglycerides are values of 200 mg/dL and above.

Change in Systolic Blood Pressure

Blood pressure is the pressure of circulating blood on the walls of blood vessels, and it is measured in mm Hg. Systolic blood pressure values of less than 120 mm Hg are considered within the normal range.

Change in Diastolic Blood Pressure

Blood pressure is the pressure of circulating blood on the walls of blood vessels, and it is measured in mm Hg. Diastolic blood pressure numbers of less than 80 mm Hg are considered within the normal range.

Change in Orthostatic Blood Pressure

Blood pressure is obtained while the participant is seated or supine, then the measurement is repeated with the participant standing. Orthostatic hypotension is indicated if systolic blood pressure decreases by 20 mmm Hg or if diastolic blood pressure decreases by 10 mm Hg with the standing measurement.

Change in Serum Catecholamine Measurements

Serum catecholamine measurements assess the amount of dopamine, norepinephrine, and epinephrine in blood. Increased catecholamines are found during times of emotional or physical stress.

Change in Glucose Tolerance

Glucose tolerance will be measured by oral glucose tolerance tests. A normal glucose level is below 140 mg/dL.

Change in Fasting Insulin Levels

The fasting insulin test is used to diagnose insulin resistance. Normal values for fasting insulin are below 25 milli-international units per liter (mIU/L).

Change in Fasting C-peptide Levels

C-peptide levels are used in diagnosing diabetes. Normal values for fasting C-peptide are between 0.5 and 2.0 nanograms per milliliter (ng/mL). Values higher than 2.0 ng/mL can indicate insulin resistance.

Full Information

NCT ID

NCT04569721

First Posted

September 25, 2020

Last Updated

July 22, 2021

Sponsor

Emory University

Collaborators

Georgia Research Alliance

1. Study Identification

Unique Protocol Identification Number

NCT04569721

Brief Title

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

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Withdrawn

Why Stopped

There was only one subject consented and it was a screen failure. No participants enrolled and study is being closed due to lack of enrollment.

Study Start Date

February 19, 2021 (Actual)

Primary Completion Date

February 2022 (Anticipated)

Study Completion Date

February 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

Georgia Research Alliance

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

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

Type 2 Diabetes

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CT guided splanchnic cryoablation

Arm Type

Experimental

Arm Description

Obese patients with type 2 diabetes receiving CT guided splanchnic cryoablation.

Intervention Type

Device

Intervention Name(s)

CT Guided Splanchnic Cryoablation

Intervention Description

The patient will be sedated and continuously monitored by the anesthesia team, who will be present for the entire procedure. The puncture site will be anesthetized with 1% Lidocaine infiltration. Following tract anesthesia, and utilizing fluoroscopic CT guidance, four cryoablation probes (Ice Rods®) will be advanced, 2 on each side. In addition, a temperature monitoring probe (Boston Scientific, Multipoint 1.5 Thermal Sensor®) will be advanced on each side. The cryoablation process will include a 10-minute freeze, followed by a 3-minute passive thaw, and a brief active thaw to facilitate probe removal. A final scan will be obtained following removal of the probes. After the procedure, a sterile dressing will be applied, and subjects will be monitored for at least 12 hours in an observation bed in the hospital post-procedure.

Primary Outcome Measure Information:

Title

Mortality

Description

The number of participant deaths will be used to assess the safety of the study procedure.

Time Frame

Month 12

Title

Number of Procedure Related Complications

Description

Time Frame

Month 12

Secondary Outcome Measure Information:

Title

Change in Hemoglobin A1c (HbA1c)

Description

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Fasting Glucose

Description

Time Frame

Baseline, Day 7, Months 1, 3, 6, and 12

Title

Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Description

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Body Weight

Description

Body weight will be measured in kilograms (kg).

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Waist Circumference

Description

Waist circumference will be measured in centimeters (cm).

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Waist-to-Hip Ratio

Description

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Total Cholesterol

Description

Measuring cholesterol is a diagnostic tool used for estimating risk of cardiac disease. Total cholesterol levels below 200 mg/dL are considered normal.

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Low-Density Lipoprotein (LDL)

Description

High levels of LDL leads to arteriosclerosis. LDL levels below 100 mg/dL are considered optimal, however, persons with diabetes or cardiac disease are advised to keep levels below 70 mg/dL.

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in High-Density Lipoproteins (HDL)

Description

HDL values between 40 and 59 mg/dL are considered normal. HDL values under 40 mg/dL are associated with increased risk of developing heart disease and stroke.

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Triglyceride Levels

Description

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Systolic Blood Pressure

Description

Time Frame

Baseline, Day 7, Months 1, 3, 6, and 12

Title

Change in Diastolic Blood Pressure

Description

Time Frame

Baseline, Day 7, Months 1, 3, 6, and 12

Title

Change in Orthostatic Blood Pressure

Description

Time Frame

Baseline, Day 7, Months 1, 3, 6, and 12

Title

Change in Serum Catecholamine Measurements

Description

Serum catecholamine measurements assess the amount of dopamine, norepinephrine, and epinephrine in blood. Increased catecholamines are found during times of emotional or physical stress.

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Glucose Tolerance

Description

Glucose tolerance will be measured by oral glucose tolerance tests. A normal glucose level is below 140 mg/dL.

Time Frame

Baseline, Months 1, 3, 6, and 12

Title

Change in Fasting Insulin Levels

Description

The fasting insulin test is used to diagnose insulin resistance. Normal values for fasting insulin are below 25 milli-international units per liter (mIU/L).

Time Frame

Baseline, Day 7, Months 1, 3, 6, and 12

Title

Change in Fasting C-peptide Levels

Description

Time Frame

Baseline, Day 7, Months 1, 3, 6, and 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John D Prologo, MD

Organizational Affiliation

Emory University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory Johns Creek Hospital

City

Johns Creek

State/Province

Georgia

ZIP/Postal Code

30097

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Percutaneous CT-guided Cryoablation of the Splanchnic Nerves

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