Clinical trial NCT04232774: Neurotronic Ablation of Arteries for the Treatment of Type 2 Diabetes Mellitus and Its Comorbidities
Official title: Neurotronic Ablation of Arteries for the Treatment of Type 2 Diabetes Mellitus and Its Comorbidities
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes Mellitus With Circulatory Complciation
Keywords: Denervation
T2DM
Hypertension
Obesity
Lead sponsor: Neurotronic, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Libra Medical
First posted: 2020-01-18
Enrollment: 22
Sex: ALL
Minimum age (years): 22
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a prospective, single-center, non-randomized, open label first-in-human (FIH) study.
Primary purpose: TREATMENT

Brief summary: The study is to assess the safety and feasibility of chemical denervation of multiple artery beds for the treatment of Type 2 diabetes (T2DM) and its comorbidities.

Detailed description: Diabetes mellitus is among the most prevalent chronic diseases, affecting 435 million persons as of 2015 with an annual death toll of 1.5 million, and the overwhelming majority of these have Type 2 diabetes mellitus (T2DM). Hypertension is a common comorbidity of diabetes and present in more than 50% of diabetic patients. The risk for cardiovascular disease (CVD) is four-fold higher in patients with both DM and hypertension as compared to the normotensive non-diabetic controls. Obesity, with a prevalence of over 500 million, is another common comorbidity of diabetes. These are chronic diseases associated with increased risks of cardiovascular disease, stroke, and decreased quality of life.

Neurotronic developed a novel catheter for denervation procedure. Chemical agent is delivered locally into the adventitial space and ablates the sympathetic nerve and nerve endings in the adventitial space of the target arteries.

The purpose of the study is to assess the safety and feasibility of chemical denervation of the target arteries for the treatment of Type 2 diabetes (T2DM) and its comorbidities.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 22 and ≤ 70 years at time of enrollment.
2. Diagnosed with uncontrolled T2DM with baseline.

   1. Fasting plasma glucose ≥ 155 mg/dl (8.6 mmol/l)
   2. HbA1c levels ≥ 7.5% and \< 10% (58-86 mmol/mol)\]
   3. On oral anti-hyperglycemic drug regimen of at least two different drug classes, and one of the two being metformin ≥ 1500 mg/day
   4. History of positive response to metformin dosage escalation, i.e., HbA1c reduction of 0.5% or more
3. Diagnosed hypertension with baseline office blood pressure of SBP of ≥ 150 mmHg and ≤ 180 mmHg and DBP ≥ 90 mmHg.
4. BMI between 27.5 and 45 kg/m2 and weight \< 400lbs.
5. Vessel diameter of 3 mm to 7 mm with a minimum arterial treatable length of 20 mm.

Exclusion Criteria:

1. T1DM or poorly controlled T2DM (defined as HbA1c \>10.0%).
2. Hypoglycemia unawareness or serious hypoglycemia with loss of consciousness or confusion sufficient to prevent self-treatment in last 6 months;
3. Diagnosed proliferative retinopathy or evidence of peripheral neuropathy.
4. Lack of appropriate treatment site or anatomy precluding the intervention of the target arteries.
5. History of prior target artery intervention including balloon angioplasty, stenting, etc.
6. Arterial stenosis \>50% of the normal diameter segment (diameter stenosis, compared to the angiographically normal proximal or distal segment).
7. 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, artery calcification)
8. 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.
9. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over the month prior to enrollment.
10. 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.
11. 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.
12. Liver transplant.
13. Gastrointestinal permanent anatomic alteration surgery
14. Bleeding disorders, such as bleeding diathesis, thrombocytopenia, and severe anemia.
15. Systemic infection that the investigator judges would pose unacceptable procedural risks to the subject.
16. Known hypersensitivity to contrast media, nickel and the chemical agent that cannot be adequately pre-medicated.
17. Occlusive peripheral vascular disease that would preclude percutaneous femoral access for the procedure.
18. Subject is depressed or on antidepressants.
19. Pregnancy or breastfeeding or plan to get pregnant in next 12 months.
20. Life expectancy of less than 12 months.
21. Unwilling or unable to comply with the follow-up study requirements.
22. Lacking capacity to provide informed consent.
23. Concurrent medical condition that would affect the investigator's ability to evaluate the patient's condition or could compromise patient safety.
24. Currently participation in another pre-market drug or medical device clinical study.

Primary outcomes:
measure: Incidence of Serious Device- and Procedure-Related Complications
timeFrame: at 30 Days post procedure
Secondary outcomes:
measure: Glycemic Control (1)
timeFrame: at baseline and at post-procedure: 2-week, 1-month, 3-month, 6-month, 12-month and 24-month follow-up visits. Also, optionally at 3-,4- and 5-year post-procedure follow-up visits.
measure: Glycemic Control (2)
timeFrame: at baseline and at post-procedure: 2-week, 1-month, 3-month, 6-month, 12-month and 24-month follow-up visits. Also, optionally at 3-,4- and 5-year post-procedure follow-up visits.
measure: Hypertension Control
timeFrame: at baseline and at post-procedure: 2-week, 1-month, 3-month, 6-month, 12-month and 24-month follow-up visits. Also, optionally at 3-,4- and 5-year post-procedure follow-up visits.
measure: Weight Control (1)
timeFrame: at baseline and at post-procedure: 2-week, 1-month, 3-month, 6-month, 12-month and 24-month follow-up visits. Also, optionally at 3-,4- and 5-year post-procedure follow-up visits.
measure: Weight Control (2)
timeFrame: at baseline and at post-procedure: 2-week, 1-month, 3-month, 6-month, 12-month and 24-month follow-up visits. Also, optionally at 3-,4- and 5-year post-procedure follow-up visits.
measure: Device Success
timeFrame: during procedure or immediately after procedure
measure: Procedure Success
timeFrame: during procedure or immediately after procedure
Other outcomes:
Locations:
city: Asunción
country: Paraguay
facility: Sanatorio Italiano - Centro de Intervenciones Endovasculares
Study officials:
affiliation: Neurotronic, Inc.
name: John Chen
role: STUDY_DIRECTOR
References: