NMDA Receptors in Motor Learning in Humans
Condition: Stroke
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to focus on enhancing upper limb recovery in patients
      post-stroke by using robotic-assisted therapy in combination with a drug to improve learning
      new motor skills.
    

Detailed description: 
      Disability after a stroke is common, leaving 65% of patients unable to use their affected
      hand in daily activities after 6 months. Frequently, these limitations can cause a decreased
      quality of life. The current standard for intense physical therapy most commonly consists of
      neurofacilitation techniques and/or task-specific training. Labor-intensive and costly
      therapy methods are critical barriers to achieving optimal functional outcomes in stroke
      survivors with motor impairments. Thus, there is a great need to find new ways to enhance the
      effectiveness of upper limb rehabilitation in patients following stroke.

      A promising approach to improving upper extremity motor function utilizing repetitive task
      practice (RTP) and behavioral shaping along with constraint of the less affected limb is
      constraint-induced movement therapy (CIMT). Two fundamental limitations of CIMT are the time
      necessary to deliver and oversee training and the excessive time in which the less affected
      limb must be constrained. RTP, in the context of CIMT appears to be effective in improving
      upper extremity motor function of patients with stroke. Alternative approaches such as
      robotic assisted therapy have been investigated. Recent evidence suggests that improvements
      in upper-extremity motor function, functional performance in daily tasks and quality of life
      are seen during a robotic-assisted physical therapy regimen.

      Activation of N-methyl-D-aspartate (NMDA) receptors is important for inducing various forms
      of synaptic plasticity. Application of D-cycloserine (a antibiotic for treating tuberculosis)
      can enhance certain models of plasticity, such as long-term potentiation. Pharmacologic
      strategies that enhance NMDA neurotransmission and working memory represent a promising
      adjuvant therapy in motor rehabilitation of patients after stroke.

      The researchers for this study have brought these observations together to generate a working
      hypothesis that D-cycloserine will enhance certain features of motor learning, information
      processing speed, episodic and working memory and that this effect can be coupled with
      physical therapy to facilitate retraining of patients to use impaired limbs to a greater
      extent and faster than they otherwise might be able to do. The researchers specifically
      hypothesize that motor (re)learning and cognition can be improved in people with post-stroke
      hemiparesis by increasing the excitability and synaptic activity of the motor cortex by
      combining D-cycloserine and robotic-assisted physical therapy.

      The purpose of this study is to understand the important factors in rehabilitation therapy
      that help improve arm function after stroke. This information may help to ultimately reduce
      disability and improve quality of life in patients with stroke.
    

Intervention name(s): D-cycloserine; Placebo; HandMentor Pro
Intervention type(s): Drug; Other; Device
Intervention description(s): D-cycloserine 100mg PO twice weekly (Monday and Wednesday) for three weeks; Placebo pill PO twice weekly (Monday and Wednesday) for three weeks; The HandMentor Pro (Kinetic Muscles Inc.) is a robotic device that has recording electrodes. The device gives feedback during various activities requiring varying levels of wrist control. The main goal of the hand robot is to improve active range of motion about the wrist and fingers and wrist control. The robotic therapy will be done over 3 consecutive weeks for 2 hours each session (days 1, 3, 5, 8, 10, 12, 15, 17 and 19, for 18 hours total).
Other intervention name(s): Seromycin
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment