Clinical trial NCT01588587: DPP-IV Inhibitors Underlying Mechanism of Cancer in Diabetic Patients
Official title: Effect of DPP-IV Inhibitors on Occurence of Cancers and the Mechanism Using AGE and RAGE in Patients With Type 2 Diabetes
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Nagaoka Red Cross Hospital
Sponsor class: OTHER
Collaborators: name: Kurume University
First posted: 2012-05-01
Enrollment: 500
Sex: ALL
Minimum age (years): 20
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 500 patients

Brief summary: Recently, DPP-IV inhibitors are used as a novel way to augment the incretin system and one of the newest classes of medications in the treatment of type 2 diabetes mellitus (T2DM). Since the DPP-IV inhibitor was first used, about 5 years have passed in USA. However, there were no major side effects including occurrence of cancers. The main mechanism for DPP-IV inhibitors is due to suppress the function of DPP-IV activity. As it is known that the suppressed DPP-IV activity is a marker for early diagnosis of cancers, the reason of disassociation is not clear.

Activation of receptor for advanced glycation endproduct (AGE) is related to sideration of cancers. Meanwhile, the DPP-IV inhibitors may be related to inhibit the activation of receptor for AGE (RAGE). Therefore, DPP-IV inhibitors may work as a cancer protective agent in diabetes by blocking the AGE-RAGE axis.

However, it is not demonstrated why DPP-IV inhibitors have no side effect of occurrence of cancer via blocking the activation of AGE-RAGE.

The investigators examined effect of DPP-IV inhibitors on frequency of cancers and the underlying mechanism using AGE and RAGE before and 5 years after administration of DPP-IV inhibitors in Japanese patients with T2DM.

Detailed description: The AGE and RAGE are measured using ELISA method in the laboratory of Department of Pathophysiology and Therapeutics of Diabetes Vascular Complications, Kurume University, School of Medicine, Japan before and for 5 years after administration of DPP-IV inhibitors.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes mellitus patients with or without cancer

  * Patients who have no treatment with DPP-IV inhibitors.
  * 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 participating in other clinical study.
  * Other than the above, patients judged inappropriate as the subjects of this study by the investigator

Primary outcomes:
measure: Frequency of cancers
timeFrame: Each one year within 5 years
Secondary outcomes:
measure: AGE concentration
timeFrame: Before and each one year within 5 years
measure: Receptor for AGE concentration
timeFrame: Before and each one year within 5 years
Other outcomes:
Locations:
city: Kurume
country: Japan
facility: Kurume University
state: Fukuoka
city: Nagaoka
country: Japan
facility: Nagaoka Red Cross Hospital
state: Niigata
Study officials:
affiliation: Nagaoka Red Cross Hospital
name: Kyuzi Kamoi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 1.Gooβen K, Gräber S. Longer-term safety of DPP-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab 2012 doi:[Epub ahead of print]. 2.Cornell S. Differentiating among incretin therapies: a multiple-target approach to type 2 diabetes. J Clin Pharm Ther 2012; 21:1365-2710. 3.Cordero OJ, Imbernon M, Chiara LD, Martinez-Zorzano VS, Ayude D, de la Cadena MP, Rodriguez-Berrocal FJ.Potential of soluble CD26 as a serum marker for colorectal cancer detection. World J Clin Oncol 2011;2: 245-61. 4.Taguchi A, Blood DC, del Toro G, Canet A, Lee DC, Qu W, Tanji N, Lu Y, Lalla E, Fu C, Hofmann MA, Kislinger T, Ingram M, Lu A, Tanaka H, Hori O, Ogawa S, Stern DM, Schmidt AM. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 2000;18;405:354-60.5.Kang R, Loux T, Tang D, Schapiro NE, Vernon P, Livesey KM, Krasinskas A, Lotze MT, Zeh HJ 3rd. The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia. Proc Natl Acad Sci U S A 2012 Apr 16. [Epub ahead of print].6.Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Sitagliptin augments protective effects of GLP-1 against advanced glycation end product receptor axis in endothelial cells. Horm Metab Res 2011; 43:731-4.