AI(I)DA Acarbose and the Subclinical Inflammation

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Placebo Controlled Investigation on Action of Acarbose on the Sub-Clinical Inflammation and Immune Response in Early Type 2 Diabetes and Atherosclerosis Risk

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00558883
• Other study ID #: AI(I)DA
• Status: Completed
• Phase: Phase 3
• First received: November 14, 2007
• Last updated: April 10, 2008
• Start date: January 2005
• Est. completion date: May 2007

Study information

• Verified date: April 2008
• Source: GWT-TUD GmbH
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

Acarbose an alphaglucosidase inhibitor changes in a complex way the transport, the digestion and the place of glucose release and absorption. As a result the intestinal milieu, the intestinal flora and the provision of enzymes in the lower small destine are changed. This should modify immune response of intestinal wall on food and its proinflammatory effects. The small intestine is the biggest immune organ of the organism. The postprandial glucose increase could have a direct effect on low-grade inflammation. Toxic effects (glucotoxicity), activation of the immune system and low grad inflammation could be reasons of developing endothelial dysfunction and affect plaque stability. The activity of the lymphocyte immune system in the intestine would be a further component, by which acarbose could take influence on diabetogenesis and atherogenesis. The question of an enterovasal axis is one of the new research concepts. As indicators of this axis considered: leucocytes, high sensitive C-reactive protein, plasminogen activator inhibitor antigen and lymphocytes sub-populations. The effect of acarbose on these parameters in the postprandial phase are not known yet.

Description:

Acarbose, an alpha-glucosidase-inhibitor, delays the release of glucose out of complex carbohydrates in the upper small intestine. The digestion of carbohydrates after acarbose intake therefore mainly takes place in the lower small intestine and colon. Through this innovative mode of action the postprandial hyperglycemia is specifically delayed and flattened. Acarbose is used for more of 15 years for the therapy of type 2 diabetes. Efficiency and safety in treating diabetes were proved in extensive studies. Until today no serious side effects under acarbose were reported, the reduction of HbA1c is 0.7-1 %. Three large prospective studies and metaanalysis resp., could prove that acarbose has a highly significant positive effect on the incidence and progression of cardiovascular disease in people with prediabetes and type 2 diabetes resp. In the STOP-NIDDM-trail in persons with prediabetes as well as in the meta-analysis in type 2 diabetes (MERIA) the event rate in the acarbose group was ~ 50 % lower. In a substudy of the STOP-NIDDM intervention study a ca. 50 % lower progression of the intima-media-thickness of the A. carotis communis was documented under acarbose in comparison with placebo. In multivariate analysis acarbose was always the most important independent determinant of vasoprotective effects. Epidemiological investigations, even as controlled prospective studies, cannot establish causal relationships. Thus the question rises wether acarbose has - besides the known therapeutic effect on postprandial hyperglycemia pleiotropic effects, which lead to the documented preventive effects on cardiovascular complications. This would be of principal importance for the use of acarbose in patients with prediabetes / type 2 diabetes and increased vascular risk. So far acarbose is the only cardiovascular oral antidiabetic drug in people with IGT.

Working hypothesis:

Acarbose changes in a complex way the transport, the digestion and the place of glucose release and absorption. As a result the intestinal milieu, the intestinal flora and the provision of enzymes in the lower small intestine are changed. This should modify immune response of intestinal wall on food and its proinflammatory effects. The small intestine is the biggest immune organ of the organism. The postprandial glucose increase could have a direct effect on low-grade inflammation. Toxic effects (glucotoxicity), activation of the immune system and low-grade inflammation could be reasons of developing endothelial dysfunction and affect plaque stability. The activity of the lymphocyte immune system in the intestine would be a further component, by which acarbose could take influence on diabetogenesis and atherogenesis. The question after an enterovasal axis is now one of the most fascinating new research concepts and basis of incretin-related drug treatment of diabetes resp. As intravasal indicator for low-grade inflammation are considered: leucocytes, high sensitive C-reactive protein (hsCRP) and plasminogen activator inhibitor active antigen (PAI1) as well as lymphocytes subpopulations. The effects of acarbose on these parameters in the postprandial phase are not known yet.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

Inclusion criteria:

In this study patients with type 2 diabetes are included, who fulfil the following criteria:

• type 2 diabetes by WHO criteria, aged 30-75

• HbA1c = 6.5 % < 8.0 % and/or 2h 75 OGTT plasma glucose = 11.1 mmol/l

• fasting leucocytes count = 6.2 GPt/l (median for newly diagnosed type 2 patients in RIAD) and/or hsCRP = 1.0 mg/dl and < 10 mg/dl (earlier 2.8 mg/dl)

• informed consent

Exclusion criteria:

Excluded were patients with one of the following criteria:

• contraindication for acarbose

• chronic gastrointestinal disease

• prior antidiabetic treatment

• intake of statins or drugs with antiinflammatory effects

• acute or chronic inflammatory diseases

• MI or stroke < 6 months before entry

• immune diseases

• neoplasia

• diseases with acute weight loss

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Inflammation
• Subclinical Inflammation
• Type 2 Diabetes Mellitus

Intervention

Drug:
• acarbose
oral application

Locations

Country	Name	City	State
Germany	GWT-TUD GmbH; Centre for Clinical Studies	Dresden

Sponsors (4)

Lead Sponsor	Collaborator
GWT-TUD GmbH	Diakonissen Krankenhaus Dresden, Germany, Technische Universität Dresden, University of Regensburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	effect of treatment of leucocyte count before and after test meal		20 weeks
Secondary	identification of gene arrays are registered of relevant pharmacodynamic structures and metabolism ways. Histological examinations of bioptats; Blood: hsCRP, PAI1; Lymphocyte subpopulations; blood lipids, plasma glucose fasting and postprandial		20 weeks