Healthy, Young Adults Clinical Trial
Official title:
Effect of Number of Remote Limb Ischemic Conditioning Cycles on Learning Enhancement in Healthy Young Adults
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.
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.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03512028 -
Remote Limb Ischemic Conditioning to Enhance Learning and Muscle Strength in Healthy Young Adults
|
Phase 1 |