Effect of Number of Remote Limb Ischemic Conditioning Cycles on Learning Enhancement
Condition: Healthy, Young Adults
MeSH terms: Ischemia
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this research study is to determine the effect of number of remote limb
      ischemic conditioning (RLIC) cycles on enhancing learning in neurologically intact young
      adults.
    

Detailed description: 
      It is now understood that the nervous system has remarkable adaptive capacity. Specifically,
      the central nervous system retains its ability to reorganize in structure and function in
      response to behavioral experience in neurologically intact people and in individuals with
      neurological injury. Cognitive and motor learning guide the adaptation of the central nervous
      system and are essential components of effective training paradigms.

      There is a growing body of literature which suggests that inducing a transient state of
      systemic ischemia has the potential to induce spinal plasticity, strengthen spared pathways
      to motorneurons, and lead to improved motor recovery following neurological injury.1,2
      Specifically, daily systemic ischemic conditioning has been shown to improve both forelimb
      and respiratory motor function in rodent models of chronic cervical spinal injury.1,3
      Moreover, systemic ischemic conditioning resulted in increased ankle strength (single
      session)2 and augmented walking speed and endurance (5 sessions)4 in humans with motor
      incomplete spinal cord injuries.

      In a related area of research, it has been shown that ischemic conditioning administered
      peripherally represents a strategy for harnessing the body's endogenous protective
      capabilities against lethal levels of ischemia. With this technique, applying brief ischemia
      and reperfusion to a remote organ or tissue results in significantly reduced damage from
      subsequent exposures to ischemia. For example, applying a tourniquet and creating hypoxia in
      a rat's hindlimb for 10 minutes reduced the extent of cardiac abnormalities following a
      sustained ischemic insult.5 This same phenomenon has been shown in humans. Applying an
      inflated blood pressure cuff to the upper or lower limb has shown efficacy for protection in
      people undergoing cardiac surgeries,6,7 undergoing elective surgery to repair abdominal
      aortic aneurysm,8 experiencing MI,9 and with symptomatic intracranial arterial stenosis.7

      The mechanisms underlying the neuroplastic and neuroprotective effects of ischemic
      conditioning are not fully understood. At this time, the literature indicates that there are
      both humoral and neural mechanisms responsible for the protection and the plasticity. It is
      clear that ischemic conditioning results in widespread physiological effects and that the
      observed effects work through multiple mechanistic pathways.

      The next translational step is to investigate whether combining ischemic conditioning with
      behavioral training has the ability to augment motor learning. Specifically, we will employ
      remote limb ischemic conditioning (via inflation/deflation of a blood pressure cuff) with the
      objective of activating the endogenous pathways shown to elicit neuroplasticity. If
      eventually effective, RLIC could have profound effect on the rehabilitation and recovery of
      motor function in people with stroke. It is important to first start this translational
      investigation in neurologically intact people in order to determine optimal protocols for
      people with stroke.

      The purpose of this study is to test the effect of number of RLIC cycles on motor learning in
      neurologically intact adults and if we can find a physiological blood marker related to
      effective administration of RLIC. We hypothesize that 3 cycles of RLIC will be sufficient to
      enhance motor leaning compared to sham conditioning, and that there will be a dose-dependent
      (number of cycles) response in learning, thus making training more efficient, more effective,
      and longer-lasting. Determining the number of cycles necessary to elicit the benefits of RLIC
      is important in developing the most effective and least burdensome treatment for future
      patients with motor deficits.
    

Intervention name(s): RLIC - 5 cycles; RLIC - 4 Cycles; RLIC - 3 Cycles; Sham conditioning; Balance training; Arm training; Sequence production training
Intervention type(s): Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral
Intervention description(s): RLIC is achieved as listed in the arm/group descriptions. RLIC is performed on visits 1-7, which occur on consecutive weekdays.; RLIC is achieved as listed in the arm/group descriptions. RLIC is performed on visits 1-7, which occur on consecutive weekdays.; RLIC is achieved as listed in the arm/group descriptions. RLIC is performed on visits 1-7, which occur on consecutive weekdays.; Sham conditioning is achieved as listed in the arm/group descriptions. Sham conditioning is performed on visits 1-7, which occur on consecutive weekdays.; All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.; All participants undergo training on a cup stacking task, learning to assemble and disassemble cup configurations as fast as they can. Participants perform the cup stacking task 5 trials per day at visits 3-7.; All participants undergo training on a discrete sequence production task. Participants learn to associate specific color and shape symbols with sequences of key presses on a keyboard. Participants perform the sequence production task for 10-15 minutes per day at visits 3-7.
Other intervention name(s): Ischemic conditioning; Ischemic conditioning; Ischemic conditioning; Cup stacking
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single blinded, randomized controlled trial
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: ischemic conditioning, motor learning