AI(I)DA Acarbose and the Subclinical Inflammation

This study has been completed.
Sponsor:
Collaborators:
Technische Universität Dresden
Diakonissen Krankenhaus Dresden, Germany
University of Regensburg
Information provided by:
GWT-TUD GmbH
ClinicalTrials.gov Identifier:
NCT00558883
First received: November 14, 2007
Last updated: April 10, 2008
Last verified: April 2008
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Subclinical Inflammation
Drug: acarbose
Phase 3

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

Resource links provided by NLM:


Further study details as provided by GWT-TUD GmbH:

Primary Outcome Measures:
  • effect of treatment of leucocyte count before and after test meal [ Time Frame: 20 weeks ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 20 weeks ]

Enrollment: 104
Study Start Date: January 2005
Study Completion Date: May 2007
Arms Assigned Interventions
Active Comparator: 1
treatment with Acarbose: 2 weeks 1 x 50mg; 2 weeks 3 x 50mg; 16 weeks 3 x 100mg
Drug: acarbose
oral application
Placebo Comparator: 2
treatment with placebo: 2 weeks 1 x 50mg 2 weeks 3 x 50mg 16 weeks 3 x 100mg
Drug: acarbose
oral application

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.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00558883

Locations
Germany
GWT-TUD GmbH; Centre for Clinical Studies
Dresden, Germany, 01187
Sponsors and Collaborators
GWT-TUD GmbH
Technische Universität Dresden
Diakonissen Krankenhaus Dresden, Germany
University of Regensburg
Investigators
Principal Investigator: Markolf Hanefeld, PhD, MD GWT-TUD GmbH, Centre for Clinical Studies
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00558883     History of Changes
Other Study ID Numbers: AI(I)DA
Study First Received: November 14, 2007
Last Updated: April 10, 2008
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Inflammation
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Acarbose
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014