Ablation treatment for Type 2 Diabetes and hypertension

Neurotronic Ablation of Arteries for the Treatment of Type 2 Diabetes Mellitus and Its Comorbidities (NECTAR IV Trial)

This study is testing a new treatment for people with Type 2 diabetes and high blood pressure to see if it can help them feel better and manage their conditions.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 21 Years to 65 Years
• Sex: All
• Sponsor: Neurotronic, Inc. (Industry-sponsored)
• Locations: 3 sites (Tbilisi and 2 other locations)
• Trial ID: NCT05369065 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of the Neurotronic Infusion Catheter for ethanol denervation of renal and hepatic arteries in patients with Type 2 Diabetes Mellitus (T2DM), hypertension, and obesity. It includes a multicenter design with two groups: a randomized, double-blind, sham-controlled cohort and a single-arm non-randomized cohort. Participants in the randomized group will be assigned to either the ablation treatment or a sham treatment, while all participants in the non-randomized group will receive the ablation treatment. The study aims to assess outcomes over a follow-up period of at least six months.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 65 with Type 2 Diabetes and hypertension who meet specific clinical criteria.

Not a fit: Patients with severe comorbidities or those outside the specified age and health criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve blood sugar control and reduce hypertension in patients with Type 2 Diabetes.

How similar studies have performed: While similar approaches have been explored, this specific method of arterial ablation for diabetes treatment is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 21 and ≤ 65 years at time of enrollment.
2. Diagnosed with T2DM with baseline:

   1. Fasting plasma glucose ≥ 140 mg/dl (7.8 mmol/l) and ≤ 270 mg/dL (15 mmol/L)
   2. HbA1c levels ≥ 7.0% and ≤ 9.0% (53-75 mmol/mol)
   3. Triglyceride level \< 400 mg/dL (4.52 mmol/L)
   4. On oral anti-hyperglycemic drug regimen of metformin. Subjects may be on additional oral anti-hyperglycemic drug of a different drug class
   5. Years of T2DM ≤ 10 years
3. Diagnosed hypertension with baseline:

   1. Office blood pressure of SBP of ≥ 140 mmHg and ≤ 180 mmHg and DBP ≥ 90 mmHg
   2. Mean 24-hour ambulatory SBP of ≥ 130 mmHg and ≤ 170 mmHg with ≥ 75% valid readings
   3. On stable oral anti-hypertension drug regimen consisting of up to a maximum of three drugs
4. BMI between 27.5 and 40 kg/m2
5. C-peptide testing: non-fasting random or stimulated C-peptide ≥ 2 ng/mL (660 pmol/L)
6. Vessel diameter of 3 mm to 6.5 mm inclusively with a minimum arterial treatable length of 20 mm in one or more of the following arteries:

   * Renal
   * Hepatic

Exclusion Criteria:

1. T1DM or poorly controlled T2DM (defined as HbA1c \> 9.0% or use insulin as medication to control glucose level).
2. Office diastolic blood pressure \< 90 mmHg.
3. Current use of \> 3 hypertension medications.
4. Currently on beta blockers or alpha blockers.
5. One or more documented hyperglycemia episodes requiring hospitalization in the 180-day prior to screening date.
6. Prior evidence of hypoglycemia unawareness or serious hypoglycemia with loss of consciousness or confusion sufficient to prevent self-treatment in last 6 months.
7. BMI \> 40 kg/m2.
8. Diagnosed proliferative retinopathy or evidence of peripheral neuropathy.
9. Lack of appropriate treatment site or anatomy precluding the intervention of the target arteries (renal and hepatic artery).
10. History of prior renal or hepatic artery intervention including balloon angioplasty, stenting, etc.
11. Arterial stenosis \>50% of the normal diameter segment (diameter stenosis, compared to the angiographically normal proximal or distal segment).
12. Any abnormality or disease in one or more of the target arteries that, per the physician assessment, precludes the safe insertion of the guiding catheter (including, but not limited to, artery aneurysm, excessive tortuosity, calcification).
13. Occlusive peripheral vascular disease that would preclude percutaneous femoral access for the procedure.
14. Known or suspected secondary hypertension, such as Cushing's disease or Cushing's Syndrome, hyperaldosteronism, pheochromocytoma, thyroid and parathyroid abnormalities, history of pre-eclampsia, onset of hypertension prior to the age of 18.
15. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over the month prior to enrollment.
16. Severe or unstable cardiovascular comorbidities, such as AMI or ACS, cardiac valve stenosis, pulmonary embolism, heart failure with NYHA Class III or IV, chronic atrial fibrillation, primary pulmonary hypertension, COPD.
17. Renal transplant, history of nephrectomy or single kidney, renal tumor/cancer, known non-functioning kidney, unequal renal size (\>2 cm difference in renal length between kidneys associated with a chronic kidney disease or a deterioration of the kidney function), chronic renal deficiency with eGFR ≤ 60ml/min/1.73m2, or on chronic renal replacement therapy.
18. Prior liver transplant.
19. Any organ transplantation procedures are planned in the 365 days following Index Procedure.
20. Gastrointestinal permanent anatomic alteration surgery.
21. Any surgical procedure within 30 days prior to Index Procedure.
22. Currently taking the following medications within 90 days prior to screening and/or there is a need or anticipated need for these medications during the study:

    1. Systemic Corticosteroids
    2. Anticonvulsants
    3. Centrally acting sympatholytics
23. Bleeding disorders, such as bleeding diathesis, thrombocytopenia, and severe anemia.
24. Use of anticoagulation therapy which cannot be discontinued from 7 days before or 14 days after the Index Procedure.
25. Any other condition(s) that would compromise the safety of the Subject or compromise study quality as judged by the investigator.
26. Significant alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to reliably quantify alcohol intake.
27. Active substance abuse, based on Investigator judgement, including inhaled or injected drugs, within 1 year prior to the initial screening.
28. Significant weight loss within the last 6 months (e.g., \> 10% total body weight loss).
29. Hepatic decompensation defined as the presence of any of the following:

    1. Serum albumin less than 3.5 g/dL
    2. International normalization ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)
    3. Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome
    4. History of esophageal varices, ascites, or hepatic encephalopathy
30. ALT or AST greater than 200 U/L.
31. Diagnosis of liver cirrhosis.
32. Chronic liver or biliary disease of the following etiology:

    1. History or diagnosis of Hepatitis B
    2. History or diagnosis of Hepatitis C
    3. History or diagnosis of current active autoimmune hepatitis
    4. History or diagnosis of primary biliary cholangitis
    5. History or diagnosis of primary sclerosing cholangitis
    6. History or diagnosis of Wilson's disease
    7. History or diagnosis of alpha-1-antitrypsin deficiency
    8. History or diagnosis of hemochromatosis
    9. History or diagnosis of drug-induced liver disease, as defined on the basis of typical exposure and history.
    10. Known bile duct obstruction.
    11. Suspected or proven liver cancer
33. History of acute or chronic pancreatitis.
34. Human immunodeficiency virus (HIV).
35. Subjects with a history of adverse reaction to heparin or heparin induced thrombocytopenia (HIT).
36. Systemic infection that the investigator judges would pose unacceptable procedural risks to the subject.
37. Known hypersensitivity to contrast media, nickel and ethanol that cannot be adequately pre-medicated.
38. Subject is depressed or on antidepressants.
39. Pregnancy or breastfeeding or plan to get pregnant in next 12 months.
40. Life expectancy of less than 5 years.
41. Unwilling or unable to comply with the follow-up study requirements.
42. Lacking capacity to provide informed consent.
43. Concurrent medical condition that would affect the investigator's ability to evaluate the patient's condition or could compromise patient safety.
44. Currently participation in another pre-market drug or medical device clinical study

Where this trial is running

Tbilisi and 2 other locations

• Israeli-Georgian Medical Research Clinic Helsicore — Tbilisi, Georgia (Recruiting)
• Tbilisi Heart and Vascular Clinic — Tbilisi, Georgia (Recruiting)
• Tbilisi Heart Center — Tbilisi, Georgia (Recruiting)

Study contacts

• Study coordinator: Yunlong Zhang, MD

Conditions Diabetes Mellitus, Type 2; Hypertension; Diabetes; Ablation; Denervation