Effect of DPP-IV Inhibitor on Glycemic Control and Autonomic Neuropathy in Adult Patients With Diabetes Mellitus

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effect of DPP-IV Inhibitor on Glycemic Control and Autonomic Neuropathy in Adult Patients With Diabetes Mellitus

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01545024
• Other study ID #: 4-Kamoi
• Status: Recruiting
• Phase: N/A
• First received: February 23, 2012
• Last updated: March 13, 2012
• Start date: September 2011
• Est. completion date: January 2013

Study information

• Verified date: February 2012
• Source: Nagaoka Red Cross Hospital
• Contact: Kyuzi Kamoi, MD
• Phone: -81-0258-28-3600
• Email: kkam-int[@]echigo.ne.jp
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationJapan: Ministry of Health, Labor and Welfare
• Study type: Observational

Clinical Trial Summary

Rocca et al. reported first that the secretion of incretins, particular GLP-1 in rat is regulated by the enteric nervous system, the afferent and efferent vagus nerves [1]. Further, Kazakos et al. [2] reported that autonomic nerve disturbance (AND) in patients with T2DM impaired the incretin effect owing to decreased GLP-1 secretion. However, Toft-Nielsen et al. [3] reported that the decreased GLP-1 responses in the patients with type 2 diabetes mellitus (T2DM) are unlikely to be related to the AND and, thus, did not support the results of Rocca et al. and Kazakos et al. Recently, Yabe at al. [4] also observed the same observations in Japanese patients with T2DM. Meanwhile, Jin et al. reported that administration of DPP-IV inhibitor recovered the disturbance of diabetic nerve dysfunction in rat [5]. However, it is unknown whether the administration of DPP-IV inhibitor effects on the AND in human, although many studies are performed to investigate the effect of the DPP-IV inhibitors on glycemic control.

Accordingly, it is significant to reinvestigate an effect of DPP-IV inhibitor on glycemic control and autonomic neuropathy in diabetic patients.

Description:

Autonomic nerve disturbance (AND) is estimated to use coefficient of variance of electrocardiographic beat-to-beat intervals (C.V. R-R). Maximal change of the C,V. R-R with from usual breathing to deep breathing at the resting was used for the evaluation of AND. Less than 2.0 % of the maximal value is estimated to have a positive to AND.

Glycemic control is estimated to measure change of HbA1c value once three months per year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 95 Years

Eligibility

Inclusion Criteria:

type 1 and 2 diabetes mellitus patients

• Patients who have AND determined by C.V. R-R.

• Outpatients regularly visiting hospital

• Patients 20 years old (gender is disregarded)

Exclusion Criteria:

Patients with a serious complication in the heart, liver or kidney

• Pregnant or possibly pregnant patients, or lactating patients

• Patients complicated with a malignant tumor at present.

• Patients participating in other clinical study.

• Other than the above, patients judged inappropriate as the subjects of this study by the investigator

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Nervous System Diseases
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sitagliptin, 50 mg once per day per os
Before and one year after treatment with DPP-IV inhibitor in diabetic patients with AND.

Locations

Country	Name	City	State
Japan	Nagaoka Red Cross Hospital	Nagaoka	Niigata

Sponsors (1)

Lead Sponsor	Collaborator
Nagaoka Red Cross Hospital

Country where clinical trial is conducted

Japan, 

References & Publications (1)

1. Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology 1999;140:1687-1694. 2. Kazakos KA, Sarafidis PA, Yovos JG. The impact of diabetic autonomic neuropathy on the incretin effect. Med Sci Monit 2008; 14:CR213-220. 3. Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic Patients. J Clin Endocrinol Metab 2001;86:3717-3723. 4. Yabe D, Watanabe K, Sugawara K, Kuwata H, Kitamoto Y, Sugizaki K, Fujiwara S, Hishizawa M, Hyo T, Kuwabara K, Yokota K, Iwasaki M, Kitatani N, Kurose T, Inagaki N, Seino Y (2011) Comparison of incretin immunoassays with or without plasma extraction: incretin secretion in Japanese patients with type 2 diabetes. J Diabetes Invest 2011;2:DOI. 5. Jin HY, Liu WJ, Park JH, Baek HS, Park TS. Effect of dipeptidyl peptidase-IV (DPP-IV) inhibitor (Vildagliptin) on peripheral nerves in streptozotocin-induced diabetic rats. Arch Med Res 2009;40:536-544.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic control	As marker of HbA1c	For one year after treatment wih DPP-IV inhibitor	Yes
Secondary	autonomic nerve disturbance	Before and after measurment with R-R CV in ECG at rest and respiratory deeping	Before and one year after treatment with DPP-IV inhibitor	Yes