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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Nagaoka Red Cross Hospital.
Recruitment status was  Recruiting
Information provided by (Responsible Party):
Kyuzi Kamoi, Nagaoka Red Cross Hospital
ClinicalTrials.gov Identifier:
First received: February 23, 2012
Last updated: March 13, 2012
Last verified: February 2012

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.

Condition Intervention
Type 2 Diabetes Mellitus
Drug: Sitagliptin, 50 mg once per day per os

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Effect of DPP-IV Inhibitor on Glycemic Control and Autonomic Neuropathy in Adult Patients With Diabetes Mellitus

Further study details as provided by Nagaoka Red Cross Hospital:

Primary Outcome Measures:
  • Glycemic control [ Time Frame: For one year after treatment wih DPP-IV inhibitor ] [ Designated as safety issue: Yes ]
    As marker of HbA1c

Secondary Outcome Measures:
  • autonomic nerve disturbance [ Time Frame: Before and one year after treatment with DPP-IV inhibitor ] [ Designated as safety issue: Yes ]
    Before and after measurment with R-R CV in ECG at rest and respiratory deeping

Estimated Enrollment: 60
Study Start Date: September 2011
Estimated Study Completion Date: January 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
DPP-IV inhibitor Drug: Sitagliptin, 50 mg once per day per os
Before and one year after treatment with DPP-IV inhibitor in diabetic patients with AND.
Other Name: Nothing

Detailed 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.


Ages Eligible for Study:   20 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Type 1 and 2 diabetic patients who have AND determined by C.V. R-R, outpatients regularly visiting hospital and more than 20 years old (gender is disregarded). Type 1 diabetic patients are treated with Epalrestat 50 mg. 150 mg t.i.d., while type 2 diabetic patients are treated with DPP-IV inhibitors.

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01545024

Contact: Kyuzi Kamoi, MD -81-0258-28-3600 kkam-int@echigo.ne.jp

Nagaoka Red Cross Hospital Recruiting
Nagaoka, Niigata, Japan, 940-2085
Contact: Kyuzi Kamoi, MD    +81-0258-28-3600    kkam-int@echigo.ne.jp   
Principal Investigator: Kyuzi Kamoi, MD         
Sponsors and Collaborators
Nagaoka Red Cross Hospital
Principal Investigator: Kyuzi Kamoi, MD Nagaoka Red Cross Hospital
  More Information

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.

Responsible Party: Kyuzi Kamoi, Investigator, Nagaoka Red Cross Hospital
ClinicalTrials.gov Identifier: NCT01545024     History of Changes
Other Study ID Numbers: 4-Kamoi
Study First Received: February 23, 2012
Last Updated: March 13, 2012
Health Authority: United States: Food and Drug Administration
Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Nervous System Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on November 24, 2015