Dextromethorphan, Amantadine and Glucose Homeostasis in Diabetes Subjects (DXM/AMT)
Type 2 Diabetes Mellitus
Drug: Dextromethorphan hydrobromide
Drug: Pacebo 1 (placebo for Amantadine)
Drug: Placebo 2 (fo Dextromethorphan)
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||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|
- Area under the blood glucose (BG) concentration-time profile [ Time Frame: from 1-3 hours post-dose (i.e. from 0-2 hours after an OGTT) ]
- Area under the blood glucose concentration-time profile [ Time Frame: 0-1 hour post-dose (i.e. before starting the OGTT) ]
- Adverse events [ Time Frame: 5 hours post-dose ]
|Study Start Date:||September 2011|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Drug: Dextromethorphan hydrobromide
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441986
|Profil Institute for Metabolic Research|
|Neuss, NRW, Germany, 41460|
|Principal Investigator:||Alin O Stirban, MD||Profil Institute for Metabolic Research|