Dextromethorphan, Amantadine and Glucose Homeostasis in Diabetes Subjects
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Dextromethorphan hydrobromide; Amantadine; Pacebo 1 (placebo for Amantadine); Placebo 2 (fo Dextromethorphan)
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Dextromethorphan hydrobromide•1 H2O; 30 mg; hard capsules; single, oral dose.; Amantadine hydrochloride 100 mg; tablets; single, oral dose.; Talets for oral use; single dose.; Capsles for oral administration; single dose.
Other intervention name(s): Dextromethorphan, Ratiopharm GmbH; Amantadine, STADA Arzneimittel AG.; P-Tabletten weiß 10 mm Lichtenstein, Winthrop Arzneimittel.; Empty capsules, Capsugel Bornem Belgium.
Intervention MeSH terms: Amantadine; Dextromethorphan
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: dextromethorphan; amantadine; blood glucose lowering effect; oral glucose tolerance test