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Endovascular Denervation for the Treatment of Type 2 Diabetes Mellitus

Sponsor
Shanghai Golden Leaf MedTec Co. Ltd (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05631561
Collaborator
(none)
30
Enrollment
1
Location
1
Arm
26.1
Anticipated Duration (Months)
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, multicenter, single group feasibility clinical trial to evaluate the safety and efficacy of Endovascular denervation for the treatment of type 2 diabetes mellitus (T2DM) using the Endovascular denervation system (Generator and Catheter).

Condition or Disease Intervention/Treatment Phase
  • Device: Endovascular denervation System (Generator and Catheter )
 N/A

Detailed Description

This is a prospective, multicenter, single group feasibility clinical trial. Patients with T2DM with poor glycemic control, glycated hemoglobin A1c (Hba1c) between 7.5% and 10.5% treatment with at least one to three oral antidiabetic drugs and/or insulin on the basis of metformin. All eligible patients will accept EDN treatment and were evaluated at 7, 30, 60, 90, 180, 365, 730 days post procedure. The primary safety endpoint is the number of composite major adverse events (MAE) * related to the study device and/or the denervation procedure during procedure and within 30 days after the procedure, the primary efficacy is Hba1c changes from baseline to 6 months post procedure.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Endovascular Denervation for the Treatment of Type 2 Diabetes Mellitus - a Feasible Clinical Trial Protocol
Actual Study Start Date :
Dec 27, 2022
Anticipated Primary Completion Date :
Aug 31, 2023
Anticipated Study Completion Date :
Feb 28, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: The endovascular denervation (EDN) group

Receive endovascular denervation (EDN)

Device: Endovascular denervation System (Generator and Catheter )
All patients receive endovascular denervation (EDN) treatment

Outcome Measures

Primary Outcome Measures

  1. The number of composite major adverse events (MAE) through 30 days post index procedure [From index procedure to 30 days post procedure]

    The primary safety endpoint is the number of composite major adverse events (MAE) * related to the study device and/or the denervation procedure during procedure and within 30 days after the procedure

  2. The changes of Hba1c from baseline to 6 months post procedure [From baseline to 6 months post procedure]

    The primary efficacy is the changes of Hba1c from baseline to 6 months post procedure.

Secondary Outcome Measures

  1. The changes of Hba1c from baseline to 1, 3, 12 and 24 months post procedure [From baseline to 1, 3, 12 and 24 months post procedure]

    The changes of Hba1c from baseline to 1, 3, 12 and 24 months post procedure

  2. Assessment of islet function at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The change of islet function (HOMA-β) from baseline at 1, 3, 6, 12 and 24 months post procedure

  3. Assessment of insulin resistance at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The change of insulin resistance (HOMA-IR) from baseline at 1, 3, 6, 12 and 24 months post procedure

  4. The changes of mean blood glucose over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of mean blood glucose over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure

  5. The changes of postprandial glucose increase over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of postprandial glucose increase over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure

  6. The changes of nocturnal glucose increase over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of nocturnal glucose increase over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure

  7. The changes of the amount of time glucose is in the target range (TIR) over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of the amount of time glucose is in the target range (TIR) over 14 days of continuous glucose monitoring at 1, 3, 6, 12 and 24 months post procedure

  8. The changes of blood lipids (triglycerides) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood lipids (triglycerides) from baseline to 1, 3, 6, 12 and 24 months post procedure

  9. The changes of blood lipids (total cholesterol) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood lipids (total cholesterol) from baseline to 1, 3, 6, 12 and 24 months post procedure

  10. The changes of blood lipids (high-density lipoprotein) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood lipids (high-density lipoprotein) from baseline to 1, 3, 6, 12 and 24 months post procedure

  11. The changes of blood lipids (low-density lipoprotein) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood lipids (low-density lipoprotein) from baseline to 1, 3, 6, 12 and 24 months post procedure

  12. The changes of liver function (ALT) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood liver function (ALT) from baseline to 1, 3, 6, 12 and 24 months post procedure

  13. The changes of liver function (AST) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood liver function (AST) from baseline to 1, 3, 6, 12 and 24 months post procedure

  14. The changes of liver function (ALP) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood liver function (ALP) from baseline to 1, 3, 6, 12 and 24 months post procedure

  15. The changes of liver function (GGT) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood liver function (GGT) from baseline to 1, 3, 6, 12 and 24 months post procedure

  16. The changes of renal function (blood urea nitrogen) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood renal function (blood urea nitrogen) from baseline to 1, 3, 6, 12 and 24 months post procedure

  17. The changes of renal function (serum creatinine) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood renal function (serum creatinine) from baseline to 1, 3, 6, 12 and 24 months post procedure

  18. The changes of renal function (eGFR) to 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of blood renal function (eGFR) from baseline to 1, 3, 6, 12 and 24 months post procedure

  19. The changes of glucose in oral glucose tolerance test (OGTT) from baseline to 6, 12, and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of glucose in oral glucose tolerance test (OGTT) from baseline to 6, 12, and 24 months post procedure

  20. The changes of insulin in oral glucose tolerance test (OGTT) from baseline to 6, 12, and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of insulin in oral glucose tolerance test (OGTT) from baseline to 6, 12, and 24 months post procedure

  21. The changes of C-peptide release tests in oral glucose tolerance test (OGTT) from baseline to 6, 12, and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of C-peptide release tests in oral glucose tolerance test (OGTT) from baseline to 6, 12, and 24 months post procedure

  22. Proportion of patients achieving target HbA1c (< 7.0% and ≤6.5%) at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    Proportion of patients achieving target HbA1c (< 7.0% and ≤6.5%) at 1, 3, 6, 12 and 24 months post procedure

  23. Proportion of patients with HbA1c < 7% without hypoglycemia/severe hypoglycemia or weight gain at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    Proportion of patients with HbA1c < 7% without hypoglycemia/severe hypoglycemia or weight gain at 1, 3, 6, 12 and 24 months post procedure

  24. The changes of in type/dose of antidiabetic drugs at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes of in type/dose of antidiabetic drugs at 1, 3, 6, 12 and 24 months post procedure

  25. The proportion of patients with drug dose reduction at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The proportion of patients with drug dose reduction at 1, 3, 6, 12 and 24 months post procedure

  26. The changes in type/dose of antidiabetic drugs and proportion of patients with drug dose reduction at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    The changes in type/dose of antidiabetic drugs and proportion of patients with drug dose reduction at 1, 3, 6, 12 and 24 months post procedure

  27. Incidence of hypoglycemia and severe hypoglycemia (blood glucose level < 3.9 mmol/L) at 1, 3, 6, 12 and 24 months post procedure [From baseline to 1, 3, 6, 12 and 24 months post procedure]

    Incidence of hypoglycemia and severe hypoglycemia (blood glucose level < 3.9 mmol/L) at 1, 3, 6, 12 and 24 months post procedure

  28. The number of new occurred significant abdominal aortic stenosis (>50% stenosis assessed by CTA) at 6 months post procedure [At 6 months post procedure]

    The number of new occurred significant abdominal aortic stenosis (>50% stenosis assessed by CTA) at 6 months post procedure

  29. The rates of device and/or procedure-related adverse event (AE) and serious adverse event (SAE) from baseline to 7 days, 1, 3, 6, 12 and 24 months post procedure [From baseline to 7days, 1, 3, 6, 12 and 24 months post procedure]

    The rates of device and/or procedure-related adverse event (AE) and serious adverse event (SAE) from baseline to 7 days, 1, 3, 6, 12 and 24 months post procedure

  30. Incidence of cardiovascular and cerebrovascular complications (3MACE, defined as cardiovascular death, myocardial infarction and ischemic stroke) at 12 and 24 months post procedure [From baseline to 12 and 24 months post procedure]

    Incidence of cardiovascular and cerebrovascular complications (3MACE, defined as cardiovascular death, myocardial infarction and ischemic stroke) at 12 and 24 months post procedure

  31. Quality of life/lifestyle assessment including EuroQOL 5 Dimensions (EQ-5D-5L) before procedure and 6 months post procedure [Before procedure to 6 months post procedure]

    Quality of life/lifestyle assessment including EuroQOL 5 Dimensions (EQ-5D-5L) before procedure and 6 months post procedure (0-100 score, 0 is the worst health status, 100 is the best health status)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Subject with age of >18 years old and<65 years old (both ends included)

  2. Subjects understood the requirements and treatments of the trial, agreed to and were able to complete all follow-up assessments required for the trial, and signed informed consent before any special trial-related tests and treatments were performed

  3. Diagnosed with T2DM for 1-15 years (according to WHO criteria)

  4. Metformin (daily dose ≥1000mg) was combined with 1-3 Oads for more than 3 months and/or insulin (no dose limit). Specific Oads were: insulin secretagogues (sulfonylureas/glinides), thiazolidinediones (TZDS) and α-glucosidase inhibitors (see Note), and the combined Oads were at least half of the maximum approved dose in the package insert

  5. The above OAD treatment is not effective for more than 3 months, and the glycosylated hemoglobin (HbA1c) level is between 7.5% and 10.5% (based on baseline examination)

  6. Body mass index (BMI) between 18 and 40kg/m2 (both ends included)

Exclusion Criteria:

  1. Type 1 diabetes or late-onset autoimmune diabetes in adults (LADA), or any secondary diabetes

  2. Previous aortic disease (e.g., aortic aneurysm or dissection) or aortic surgery (including celiac artery denervation)

  3. Baseline CTA showed aortic aneurysm or dissection, or anatomical abnormalities of the hepatic artery and its branches, or other abnormal vascular structure/status (e.g., severe tortuosity or stenosis of the artery, intraval thrombus, or unstable plaque) deemed by the investigator to be unsuitable for vascular ablation.

  4. More than 2 self-reported or documented episodes of severe hypoglycemia in the past 6 months (defined as hypoglycemia with severe cognitive impairment requiring assistance from another person)

  5. Have had more than one documented episode of hyperglycemia requiring hospitalization in the past 6 months, including diabetic ketoacidosis, hyperosmolar coma, etc

  6. Severe diabetic complications, such as retinal, renal, vascular, neuropathy, and diabetic foot, were considered by the investigator to be ineligible for enrollment in this trial

  7. Major cardiovascular and cerebrovascular events (MACCE) within the past 6 months, including cerebrovascular accident (CVA), transient cerebral ischemia (TIA), heart failure (NYHA class III-IV), acute myocardial infarction, or unstable angina requiring hospitalization (including previous coronary artery bypass grafting or coronary stent implantation); And uncontrolled or severe arrhythmias

  8. Severe autonomic neuropathy (orthostatic hypotension, gastroparesis syndrome, etc.)

  9. Untreated or uncontrolled high blood pressure (SBP≥160mmHg or DBP≥100mmHg), or low blood pressure (BP < 90/50 MMHG)

  10. A history of renal insufficiency or failure with a baseline estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2 (see Note c of the Clinical Data collection Table in Table 5-2 for the eGFR formula)

  11. Chronic active hepatitis, severe hepatobiliary disease (including cirrhosis), or hepatic insufficiency (alanine and/or aspartate aminotransferase > 3 times the upper limit of normal or serum total bilirubin > 2 times the upper limit of normal)

  12. Acute and chronic pancreatitis during screening and baseline periods

  13. Acute systemic infections during the screening and baseline periods

  14. Bleeding tendency or coagulopathy (PT, APTT, or INR > 2 times the upper limit of normal; Platelet count < 80×109/L or ≥ 700×109/L)

  15. Active GI ulcer or GI bleeding within 3 months before baseline

  16. Symptomatic cholelithiasis (including cholecystolithiasis, extrahepatic bile duct stones, and intrahepatic bile duct stones) but without effective treatment such as cholecystectomy, choledocholithotomy, internal drainage or external drainage

  17. Hyperthyroidism, hypothyroidism, acromegaly, Cushing's syndrome and other endocrine and metabolic diseases

  18. Autoimmune diseases

  19. Diagnosed with a high risk of malignancy or cancer development/recurrence, or expected life expectancy < 12 months

  20. History of major surgical procedures within the past 3 months

  21. A condition or concomitant medical condition, such as hemoglobinopathy or hemolytic anemia, that could have prevented the primary end point from being assessed

  22. Patients with mental illness who are unable to cooperate

  23. Received treatment with a GLP-1 receptor agonist, DPP-4 inhibitor, or SGLT-2 inhibitor within 3 months before the screening period

  24. Received systemic or intra-articular glucocorticoids (other than topical, inhaled, or eye drops) within 3 months before the screening period

  25. Use of weight-loss medications such as orlistat or other possible treatments for weight loss (weight-loss tea/herbal medicine/acupuncture, etc.) within 3 months before the screening period

  26. Prior or anticipated bariatric surgery such as subtotal gastrectomy/liposuction

  27. Receipt of central sympathetic inhibitors or anticonvulsants within 3 months prior to or anticipated during the screening period

  28. Long-term anticoagulation therapy is required but preoperative heparin bridging anticoagulation is not possible

  29. Weight gain of more than 10% in the past 3 months

  30. Allergy to or contraindication to contrast media, and inadequate pretreatment, as judged by the investigator

  31. A known history of allergy to the study device (containing polytetrafluoroethylene or Nitinol) or to medications associated with the trial protocol

  32. Were participating in other clinical studies or were participating in clinical studies within 3 months before enrollment

  33. Expect to participate in a clinical trial of another drug or medical device within 24 months after baseline surgery

  34. Pregnant or lactating women, or those planning to become pregnant within the next 2 years (all women of childbearing age must undergo a pregnancy test within 7 days before baseline surgery)

  35. Drastic changes in diet and exercise habits are expected during the study (due to religious/work needs/weight loss, etc.)

  36. Irregular day and night work (night shift workers)

  37. History of alcohol/drug/substance abuse

  38. Scheduled periodic blood product therapy or severe blood loss during the previous 3 months/study period

  39. According to the investigator's judgment, there is any situation that affects the safety of the subjects or interferes with the evaluation of the test results

  40. Subjects had aortic aneurysm or aortic dissection confirmed on angiography before EDN

  41. The subject's vascular structure and conditions were considered by the investigator to be unsuitable for ablation (e.g., severe tortuosity or stenosis of the artery, abnormal vascular anatomy, intracavinal thrombus, or unstable plaque).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Zhongda Hospital, Southeast University Nanjing Jiangsu China 210009

Sponsors and Collaborators

  • Shanghai Golden Leaf MedTec Co. Ltd

Investigators

  • Principal Investigator: Gao-Jun Teng, MD, Zhongda Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Shanghai Golden Leaf MedTec Co. Ltd
ClinicalTrials.gov Identifier:
NCT05631561
Other Study ID Numbers:
  • MLWY-S220501
First Posted:
Nov 30, 2022
Last Update Posted:
Jan 4, 2023
Last Verified:
Jan 1, 2023
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Shanghai Golden Leaf MedTec Co. Ltd
Type 2 Diabetes Mellitus
Endovascular denervation
Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2

Study Results

No Results Posted as of Jan 4, 2023