Clinical trial NCT05673668: Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes Mellitus
Official title: Clinical Mechanism of Endovascular Denervation (EDN) for the Treatment of Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Mellitus (T2DM)
Keywords: Type 2 Diabetes Mellitus
Endovascular denervation
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2023-01-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, single-center, single-arm, self-controlled study to evaluate the effects of endovascular denervation (EDN) on insulin secretory function and insulin sensitivity in the treatment of type 2 diabetes mellitus (T2DM) .

Detailed description: This is a prospective, single-center, single-arm, self-controlled study. Patients with diagnosed T2DM and poor glycemic control (i.e.. glycated hemoglobin A1c (HbA1c) between 7.5% and 10.5% despite one to three oral antidiabetic drugs (OAD) and/or insulin on the basis of metformin. All included subjects will accept EDN treatment and were followed up at 7, 30 days and 3, 6, 12 months. The primary objectives were evaluate the effects of EDN on insulin secretory function and insulin sensitivity in the treatment of T2DM.

Eligibility criteria: Inclusion Criteria:

1. Subject with age of #18 years old and#75 years old (both ends included)
2. Subject (or legal guardian) understands the requirements and treatment of this clinical trial and agrees to and is able to complete the trial
3. Diagnosed with T2DM for ≤15 years (according to WHO criteria)
4. On the basis of metformin (daily dose ≥1000mg), using a combination of 1-3 OADs for more than last 3 months, with or without insulin (dose not limited). Defined OADs were: sulfonylureas/ glienides, thiazolidinediones and α-glycosidase inhibitors
5. Glycosylated hemoglobin (HbA1c) levels between 7.5% and 10.5% (based on baseline tests)
6. Body mass index (BMI) ≥ 18 and ≤40kg/m2

Exclusion Criteria:

1. T1DM or any secondary diabetes
2. History of aortic disease (such as aortic aneurysm or aortic dissection) or aortic surgery (including celiac artery dissection)
3. Baseline CTA examination revealed aortic aneurysm or aortic dissection, or abnormal anatomical structure of hepatic artery and its branches, or other vascular structure/status abnormalities (such as severe tortuosity or narrowing of the artery, endovascular thrombosis or unstable plaque, etc.) that were not suitable for endovascular denervation as determined by the researcher
4. More than 2 self-reported or documented events of severe hypoglycemia (defined as hypoglycemia with severe cognitive impairment requiring assistance) within the past 6 months
5. Patients who had a major cardiovascular and cerebrovascular event (MACCE), major surgery, severe infection, gastrointestinal bleeding, and acute pancreatitis in the past 6 months
6. Severe autonomic neuropathy (postural hypotension, etc.)
7. Severe liver insufficiency (ALT and/or AST above 3 times the normal upper limit or serum total bilirubin above 2 times the normal upper limit), renal insufficiency (eGFR \< 60mL/ min/1.73m2). eGFR calculation formula is shown in Note e of Table 4.3 Data collection table.), chronic pancreatitis, cocoagulation disorder (PT, APTT or INR higher than 2 times of the normal upper limit; Platelet count \< 80×109/L or ≥ 700×109/L) and malignant tumors
8. Suffering from mental illness and unable to cooperate
9. Pregnant
10. There were conditions that the researchers determined will affect the safety of the subjects or interfere with the evaluation of the test results
11. Patients not eligible for MRI (e.g. paramagnetic metal implants, claustrophobia, etc.)
12. Participating in or currently participating in other clinical studies within 3 months prior to enrollment

Primary outcomes:
measure: Changes of islet secretory function (HOMA-β)
timeFrame: From baseline to 6 months
Secondary outcomes:
measure: Incidence of device or procedure-related major adverse events
timeFrame: From baseline to 12 months post procedure
measure: Changes in Hba1c
timeFrame: From baseline to 12 months post procedure
measure: Changes in the time in range (TIR) over 14 days of glucose
timeFrame: From baseline to 12 months post procedure
measure: Changes in the area under OGTT insulin release curve
timeFrame: From baseline to 12 months post procedure
measure: Changes in the area under OGTT C-peptide release curve
timeFrame: From baseline to 12 months post procedure
measure: Changes in liver fat content
timeFrame: From baseline to 6 months post procedure
measure: Changes in liver function
timeFrame: From baseline to 6 months post procedure
measure: Changes in blood lipids
timeFrame: From baseline to 12 months post procedure
measure: Changes in the gastric emptying
timeFrame: From baseline to 12 months post procedure
measure: Changes in insulin sensitivity
timeFrame: From baseline to 6 months post procedure
measure: Changes in metabolic-related hormones
timeFrame: From baseline to 6 months post procedure
measure: Changes in plasma cytokines
timeFrame: From baseline to 6 months post procedure
measure: Changes in blood and fecal metabolome
timeFrame: From baseline to 6 months post procedure
measure: Changes in fecal microbiota
timeFrame: From baseline to 6 months post procedure
measure: Change of sympathetic nervous system activity
timeFrame: From baseline to 6 months post procedure
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital, Southeast University
state: Jiangsu
Study officials:
affiliation: Zhongda Hospital
name: Gaojun Teng, MD
role: PRINCIPAL_INVESTIGATOR
References: