AI(I)DA Acarbose and the Subclinical Inflammation

NCT ID: NCT00558883

Last Updated: 2008-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2007-05-31

Brief 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.

Detailed 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.

Conditions

Type 2 Diabetes Mellitus; Subclinical Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

treatment with Acarbose: 2 weeks 1 x 50mg; 2 weeks 3 x 50mg; 16 weeks 3 x 100mg

Group Type: ACTIVE_COMPARATOR

acarbose

Intervention Type: DRUG

oral application

2

treatment with placebo: 2 weeks 1 x 50mg 2 weeks 3 x 50mg 16 weeks 3 x 100mg

Group Type: PLACEBO_COMPARATOR

acarbose

Intervention Type: DRUG

oral application

Interventions

acarbose

oral application

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technische Universität Dresden

OTHER

Sponsor Role: collaborator

Diakonissen Krankenhaus Dresden, Germany

UNKNOWN

Sponsor Role: collaborator

University of Regensburg

OTHER

Sponsor Role: collaborator

GWT-TUD GmbH

OTHER

Sponsor Role: lead

Principal Investigators

Markolf Hanefeld, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

GWT-TUD GmbH, Centre for Clinical Studies

Locations

GWT-TUD GmbH; Centre for Clinical Studies

Dresden, , Germany

Countries

Germany

Other Identifiers

AI(I)DA

Identifier Type: -

Identifier Source: org_study_id