NCT01441986

Dextromethorphan, Amantadine and Glucose Homeostasis in Diabetes Subjects

A Phase IIa, Double-blind, Placebo-controlled, Randomised, Fourfold Crossover Study to Investigate the Glucose Lowering Effects of Dextromethorphan and Amantadine in Subjects With Type 2 Diabetes Mellitus (T2DM) After an Oral Glucose Tolerance Test

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Profil Institut für Stoffwechselforschung GmbH · Industry
• Sex: Male
• Age: 45 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this trial is to demonstrate that dextromethorphan (DXM) and amantadine compared to placebo exert blood glucose (BG) lowering effects following an oral glucose tolerance test (OGTT) in male subjects with T2DM.

Detailed description

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia due to an impaired insulin activity (insulin resistance) or a reduced insulin production by the pancreas. The restoration of adequate insulin secretion represents one of the goals of several antidiabetic therapies such as sulfonylureas or incretin mimetics. Lowering blood glucose in type 2 diabetes mellitus (T2DM) prevents complications, microvascular complications in particular. Weight reduction is also a fundamental target in the treatment of T2DM; however, achieving weight loss through lifestyle measures is difficult, and the problem of obesity is often exacerbated by therapy with glucose-lowering agents such as insulin, that cause weight gain. Pancreatic ß- cells are part of the pancreatic islets, of which 1-2 millions are located within the human pancreas. Interestingly, pancreas function is controlled in part by the central nervous system and ß- cells have many features in common with neurons, including the expression of tyrosine hydroxylase (TH), neural guidance molecules, such as Eph receptors and ephrins, neural cell adhesion molecules, such as N-Cadherin and NCAM (Neural Cell Adhesion Molecule), and NMDA (N-Methyl-D-Aspartate)-type glutamate receptors. Thus, it has been hypothesized that some drugs available for manipulating the central nervous system(CNS) may also act on the pancreatic ß- cells and may be of use for T2DM and MODY treatment. NMDA receptors represent key targets for drugs against several neuronal diseases with excitotoxicity as a contributing mechanism, such as Parkinson's and Alzheimer disease, as well as for the therapy of CNS-controlled disease symptoms, such as coughing. Glutamate NMDA receptors are transmembrane, excitatory cell surface receptors at the level of the CNS and pancreatic islets. NMDA antagonists thus exert a preponderantly antiexcitatory effect on the CNS and decrease the central activation of the adrenal gland. This potentially leads to indirect effects on pancreatic cells and insulin secretion, but even direct effects on pancreatic ß-cells have been suggested by the antagonism of pancreatic NMDA receptors.

Conditions

• Type 2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Dextromethorphan hydrobromide	Dextromethorphan hydrobromide•1 H2O; 30 mg; hard capsules; single, oral dose.
DRUG	Amantadine	Amantadine hydrochloride 100 mg; tablets; single, oral dose.
DRUG	Pacebo 1 (placebo for Amantadine)	Talets for oral use; single dose.
DRUG	Placebo 2 (fo Dextromethorphan)	Capsles for oral administration; single dose.

Timeline

• Start date: 2011-09-01
• Primary completion: 2012-05-01
• Completion: 2012-05-01
• First posted: 2011-09-28
• Last updated: 2012-07-12

Locations

1 site across 1 country: Germany