The Influence of Glutamate on Memory in Humans

Overview

The hippocampus is particularly laden with n-methyl-d-aspartate (NMDA) receptors, and is at the same time one of the most important sites in declarative memory. The rationale of this study is that the NMDA partial agonist D-Cycloserine will promote learning compared to a placebo. On the other hand, the NMDA receptor antagonist Memantine might lead to reduced memory. We believe that the influence of NMDA receptors on memory can be determined via acute co-activation of the NMDA receptors with Cycloserine® (King Pharmaceuticals Ltd, active ingredient: DCycloserin, dose: 250 mg) and Memantine (Axura®, Merz, active ingredient: Memantine, dose: 20 mg)on both a behavioral and functional (fMRI) level.

Full Title of Study: “The NMDA Receptor Co-agonist D-cycloserine Accelerates Associative Learning in the Human Hippocampal CA Region”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: August 2011

Interventions

  • Drug: Sugar pill
    • 250 mg, one dose, 60 min prior
  • Drug: Sugar pill
    • 250 mg, one dose, 60 min prior
  • Drug: Sugar pill
    • 20 mg, one dose, 8 hours prior
  • Drug: Sugar pill
    • 20 mg, one dose, 8 hours prior
  • Drug: Glutamic Acid
    • 250 mg, one dose, 60 minutes prior
  • Drug: Glutamic Acid
    • 250 mg, one dose, 60 minutes prior
  • Drug: Memantine
    • 20 mg, one dose, 8 hours prior
  • Drug: Memantine
    • 20 mg, one dose, 8 hours prior

Arms, Groups and Cohorts

  • Placebo Comparator: Sugar pill, behavioral glutamic acid
    • Placebo condition for D-Cycloserine
  • Placebo Comparator: Sugar pill, fMRI, glutamic acid
    • Placebo condition for D-Cycloserine, fMRI
  • Placebo Comparator: Sugar pill, memantine, behavioral
    • Placebo condition Memantine, behavioral
  • Placebo Comparator: Sugar pill, memantine, fMRI
    • Placebo condition Memantine, fMRI
  • Active Comparator: D-Cycloserine behavioral
  • Active Comparator: D-Cycloserine, fMRI
  • Active Comparator: Memantine, behavioral
  • Active Comparator: Memantine, fMRI

Clinical Trial Outcome Measures

Primary Measures

  • fMRI during learning task
    • Time Frame: once at drug administration

Participating in This Clinical Trial

Inclusion Criteria

  • German native language or native language level – Able to give written informed consent – right-handed Exclusion Criteria:

  • inability to give written informed consent, underaged minors, contractually incapable persons, persons in legal custody – any psychiatric, neurological or internal illness – hematoporphyria (enzyme sickness) – intake of medication (except oral contraceptives) – simultaneous participation in other clinical studies – hypersensitivity to Memantine or other anti-dementia substances, or to D-Cycloserine – alcohol abuse – epilepsy – depression – serious anxiety or psychosis – serious kidney insufficiency – intake of Ethionamide or Isoniazide – pregnancy or women who are nursing – liver or kidney problems – intake of NMDA-antagonists, such as Amantadine, Ketamine, or Dextromethorphan – vegetarians – stomach ulcer, if treated with medication – renal tubular acidosis – urinary infections (with proteus bacteria) – recent heart attack, heart failure, or uncontrolled high blood pressure – intake of L-Dopa, dopaminergic agonists, and anticholinergics – intake of barbiturates, spasmolytics, Phenytoin, Amantadine, oral coagulators, warfarin, HCT (Hydrochlorothiazide) – heart or cranial operations – pacemaker, medication pump (such as insulin pump), hearing aid, removable prosthodontics – metal in or on body (such as acupuncture needles, artificial limbs, stents, metal splints, clips, implanted electrodes, tattoos, or piercings) – claustrophobia

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 35 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University Hospital, Bonn
  • Provider of Information About this Clinical Study
    • Principal Investigator: Rene Hurlemann, MD – University Hospital, Bonn

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