The Ameliorative Effects of GLP-1RA on Diabetic Cardiac Autonomatic Neuropathy

Type 2 Diabetes Clinical Trial

Official title:

The Ameliorative Effects of GLP-1RA on Diabetic Cardiac Autonomatic Neuropathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06461377
• Other study ID #: 2023-SR-611
• Status: Recruiting
• Phase: Phase 4
• Start date: June 13, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: jianbo Li, MD/PhD
• Phone: 13951750648
• Email: ljbzjlx18[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diabetic cardiac autonomic neuropathy (DCAN) is a common chronic complication that reduces survival in patients with diabetes. Epidemiological surveys have shown that the prevalence of DCAN is 25-75% in people with type 2 diabetes. The onset of DCAN is insidious and easy to be ignored in the early stage. With the progression of the disease, the following clinical symptoms gradually appear, including reduced heart rate variability, exercise intolerance, resting tachycardia, orthostatic hypotension, painless myocardial infarction and even sudden death, which seriously endanger the life and health of type 2 diabetes patients. Existing literature has shown that glucagon-like peptide-1 receptor agonist (GLP-1RA) can improve diabetic peripheral neuropathy and diabetic cognitive dysfunction, but there are few studies on improving diabetic autonomic neuropathy. Insulin resistance is an important risk factor for DCAN. Patients with type 2 diabetes are characterized by insulin resistance, and GLP-1RA is recognized as a drug to improve insulin resistance and control blood sugar in patients with diabetes. In this study, GLP-1RA was used to intervene patients with type 2 diabetes, and the changes in blood sugar control and insulin resistance status of patients were followed up. Special attention was paid to the improvement of autonomic neuropathy in diabetic patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients aged 18-70 years

2. Patients with T2DM who meet the diagnostic guidelines

3. The patient signed the relevant informed consent form

4. Being overweight or obese

Exclusion Criteria:

1. <18 years old

2. Pregnant or lactating women

3. Acute and chronic pancreatitis

4. Recent acute complications of diabetes

5. Arrhythmia or taking drugs that affect heart rate

6. Thyroid disease

7. Severe organ dysfunction

8. Denial of informed consen

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetic Neuropathies
• Type 2 Diabetes

Intervention

Drug:
• Glucagon-like peptide-1 receptor agonist:Semaglutide
The GLP-1RA intervention group was given subcutaneous injection of GLP-1RA for 3 months, while the control group was not given GLP-1RA intervention

Locations

Country	Name	City	State
China	the First Affiliated Hospital of Nanjing Medical University	Nanjing	??

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (15)

Aksu T, Gupta D, Pauza DH. Anatomy and Physiology of Intrinsic Cardiac Autonomic Nervous System: Da Vinci Anatomy Card #2. JACC Case Rep. 2021 Apr 21;3(4):625-629. doi: 10.1016/j.jaccas.2021.02.018. eCollection 2021 Apr. — View Citation

Balcioglu AS, Muderrisoglu H. Diabetes and cardiac autonomic neuropathy: Clinical manifestations, cardiovascular consequences, diagnosis and treatment. World J Diabetes. 2015 Feb 15;6(1):80-91. doi: 10.4239/wjd.v6.i1.80. — View Citation

Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes. 2014 Feb 15;5(1):17-39. doi: 10.4239/wjd.v5.i1.17. — View Citation

Goh JK, Koh L. Evaluating treatment options for cardiovascular autonomic neuropathy in patients with diabetes mellitus: a systematic review. Diabetol Int. 2023 Apr 25;14(3):224-242. doi: 10.1007/s13340-023-00629-x. eCollection 2023 Jul. — View Citation

Jorgensen JR, Thompson L, Fjord-Larsen L, Krabbe C, Torp M, Kalkkinen N, Hansen C, Wahlberg L. Characterization of Meteorin--an evolutionary conserved neurotrophic factor. J Mol Neurosci. 2009 Sep;39(1-2):104-16. doi: 10.1007/s12031-009-9189-4. Epub 2009 Mar 4. — View Citation

Kapa S, DeSimone CV, Asirvatham SJ. Innervation of the heart: An invisible grid within a black box. Trends Cardiovasc Med. 2016 Apr;26(3):245-57. doi: 10.1016/j.tcm.2015.07.001. Epub 2015 Jul 9. — View Citation

Kaze AD, Yuyun MF, Fonarow GC, Echouffo-Tcheugui JB. Cardiac autonomic dysfunction and risk of incident stroke among adults with type 2 diabetes. Eur Stroke J. 2023 Mar;8(1):275-282. doi: 10.1177/23969873221127108. Epub 2022 Nov 1. — View Citation

Kikel-Coury NL, Brandt JP, Correia IA, O'Dea MR, DeSantis DF, Sterling F, Vaughan K, Ozcebe G, Zorlutuna P, Smith CJ. Identification of astroglia-like cardiac nexus glia that are critical regulators of cardiac development and function. PLoS Biol. 2021 Nov 18;19(11):e3001444. doi: 10.1371/journal.pbio.3001444. eCollection 2021 Nov. — View Citation

Lee HS, Han J, Lee SH, Park JA, Kim KW. Meteorin promotes the formation of GFAP-positive glia via activation of the Jak-STAT3 pathway. J Cell Sci. 2010 Jun 1;123(Pt 11):1959-68. doi: 10.1242/jcs.063784. Epub 2010 May 11. — View Citation

Maser RE, Lenhard MJ. Cardiovascular autonomic neuropathy due to diabetes mellitus: clinical manifestations, consequences, and treatment. J Clin Endocrinol Metab. 2005 Oct;90(10):5896-903. doi: 10.1210/jc.2005-0754. Epub 2005 Jul 12. — View Citation

Mehta K, Behl T, Kumar A, Uddin MS, Zengin G, Arora S. Deciphering the Neuroprotective Role of Glucagon-like Peptide-1 Agonists in Diabetic Neuropathy: Current Perspective and Future Directions. Curr Protein Pept Sci. 2021;22(1):4-18. doi: 10.2174/1389203721999201208195901. — View Citation

Takaku S, Tsukamoto M, Niimi N, Yako H, Sango K. Exendin-4 Promotes Schwann Cell Survival/Migration and Myelination In Vitro. Int J Mol Sci. 2021 Mar 15;22(6):2971. doi: 10.3390/ijms22062971. — View Citation

Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003 May;26(5):1553-79. doi: 10.2337/diacare.26.5.1553. — View Citation

Williams SM, Eleftheriadou A, Alam U, Cuthbertson DJ, Wilding JPH. Cardiac Autonomic Neuropathy in Obesity, the Metabolic Syndrome and Prediabetes: A Narrative Review. Diabetes Ther. 2019 Dec;10(6):1995-2021. doi: 10.1007/s13300-019-00693-0. Epub 2019 Sep 24. Erratum In: Diabetes Ther. 2019 Oct 4;: — View Citation

Wink J, van Delft R, Notenboom RGE, Wouters PF, DeRuiter MC, Plevier JWM, Jongbloed MRM. Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation. Auton Neurosci. 2020 Sep;227:102674. doi: 10.1016/j.autneu.2020.102674. Epub 2020 May 16. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	heart rate variability(HRV)	All participants were given ambulatory electrocardiogram.The time domain analysis and frequency domain analysis of heart rate variability are included in the holter ECG report.	baseline and 12 weeks later
Secondary	E/I difference	Take an average of 6 deep breaths per minute, record the difference between the maximum heart rate and the minimum heart rate during deep breathing	basline and 12 weeks later
Secondary	30/15 ratio	The heart rate in lying position was measured, and the R-R interval in more than 30 beats was measured after standing, and the ratio between the longest R-R interval in the 25-35 beats and the shortest R-R interval in the 10-15 beats after standing was calculated	basline and 12 weeks later
Secondary	Valsalva action	After deep inhalation, hold your breath as much as possible, and then blow air into the modified sphygmomanometer to keep the pressure of the sphygmomanometer at 40mmHg, continue for 10-15s, and then relax for 1 minute, a total of 3 minutes. At the same time, ECG was recorded to record the ratio of maximum heart rate to minimum heart rate	basline and 12 weeks later
Secondary	the difference between lying and Orthostatic blood pressure	Blood pressure was measured in the supine position. The patient was asked to stand immediately, and blood pressure was measured at the first and fifth minutes	basline and 12 weeks later
Secondary	grip strength tests	First, the basic blood pressure and the maximum grip strength were measured, and the blood pressure was measured after 5 minutes of continuous hard clenching with the grip apparatus (the force used was 30% of the maximum grip strength measured), and the blood pressure difference was calculated	basline and 12 weeks later
Secondary	BMI	It is calculated by dividing a person's weight in kg by their height in meters squared	basline and 12 weeks later
Secondary	FBG	Fasting glucose	basline and 12 weeks later
Secondary	Fins	Fasting insulin	basline and 12 weeks later
Secondary	Fc-peptide	Fasting c-peptide	basline and 12 weeks later
Secondary	HOMA-IR	calculated by HOMA Calculator v2.2.3	basline and 12 weeks later
Secondary	HbA1c	Reflect the average blood sugar of 3 months	basline and 12 weeks later
Secondary	Total cholesterol	one of serum biochemical index	basline and 12 weeks later
Secondary	triglyceride	one of serum biochemical index	basline and 12 weeks later
Secondary	HDL	high-density lipoprotein,one of serum biochemical index	basline and 12 weeks later
Secondary	LDL	low density lipoprotein,one of serum biochemical index	basline and 12 weeks later
Secondary	UA	Uric Acid,one of serum biochemical index	basline and 12 weeks later
Secondary	creatinine	one of serum biochemical index	basline and 12 weeks later
Secondary	eGFR	Estimated glomerular filtration rate,one of serum biochemical index	basline and 12 weeks later
Secondary	Urinary trace albumin/urinary creatinine	urine protein test urine protein urine protein test	basline and 12 weeks later