Table 4.

Clinical trials of remote ischemic conditioning (RIC) targeting other cerebral diseases

Name of study	Type of patients/pathology	size and phase of study	Primary outcomes	Secondary outcomes	RIC protocol*	Main results/observations	Status	Ref
no name	Symptomatic intracranial arterial stenosis	proof-of-concept study, 68 patients with symptomatic intracranial arterial stenosis	stroke recurrence	time to which modified Rankin scale recovers to 0–1	5 cycles applied bilaterally and daily for 300 days	RIC improvement of brain perfusion and reduction from 26.7% to 7.9% of stroke recurrence at day 300	completed	[121]
no name	Symptomatic intracranial arterial stenosis	58 octo and nonagenarian patients with symptomatic intracranial arterial stenosis	stroke recurrence	improvement of the NIHSS score (≥ 8 points or ≤ 1 point from the baseline) or modified Rankin scale of 0–2	5 cycles applied bilaterally and daily for 180 days	no clear effect: 2 infarctions and 7 transient ischemic attacks in RIC group while 8 infarctions and 11 transient ischemic attacks in sham group	completed	[122]
no name	Middle cerebral artery stenosis	pilot study, 10 patients with unilateral MCA stenosis and 24 healthy volunteers	safety and feasibility	heart rate, oxygenation index or mean flow velocity	5 cycles (single application)	no effect on heart rate, oxygenation index or mean flow velocity in MCA stenosis patients, but reduction on blood pressure in healthy volunteers	completed	[123]
no name	Cervical spondylotic myelopathy patients prior to undergoing elective decompression surgery	pilot study, 40 patients	safety and feasibility for a larger clinical trial	Median nerve somatosensory- evoked potentials (SEPs) S100ß and neuron-specific enolase plasma levels	3 cycles (single application before surgery—preconditioning)	decrease of S100ß plasma concentration	completed	[124]
no name	Aneurysmal subarachnoid hemorrhage (SAH)	pilot study 4 patients	Cerebral hemodynamic and metabolic features	not applicable	4 cycles applied in non-consecutive days 2 to 12 days following SAH (leg)	Reduction of lactate/pyruvate ration and glycerol levels in the brain; increase on intracranial pressure and decrease the mean velocities of middle cerebral artery	completed	[125]
no name	Aneurysmal subarachnoid hemorrhage (SAH)	phase I, 20 patients	safety and feasibility for a larger clinical trial (development of deep venous thrombosis, bruising, or injury to the conditioned limb)	development of new neurological deficits or cerebral infarct and neurological features at follow-up	4 cycles applied every other day for 12 days (leg)	RIC procedure is safe and feasible	completed	[126]
no name	Aneurysmal subarachnoid hemorrhage (SAH)	phase Ib, 33 patients	development of venous thrombosis or injury in the limb, safety	Transcranial Doppler spasm, delayed cerebral ischemia and 3 month modified Rankin scale	3 cycles** applied every 24 or 48 h during 14 days (leg)	RIC procedure is safe and feasible, with no difference in the analyzed parameters	completed	[127]
RICH-1	Intracranial hemorrhage	Randomized pilot study	safety	Hematoma and perihematomal edema volume, hematoma expansion	4 cycles daily for one week	cranial tomography will be performed at days 1, 3, 7 and 14 after stroke onset	ongoing	[128]
no name	Small vessel disease—Mild cognitive impairment	pilot study, 30 patients	change in brain lesions	changes of cognitive function, plasma biomarkers, and cerebral hemodynamic parameters at 1-year follow-up	5 cycles twice a day for 1 year	RIC decreased white matter hyperintensities, improved visuospatial and executive abilities and reduced plasma levels of tryglycerides, total cholesterol, LDL and homocysteine	completed	[129]
no name	Subcortical ischemic vascular dementia	pilot study, 37 patients	change in neuropsychological assessments	Changes in high-sensitive C reactive protein concentration, white matter lesion volume, diffusion tension imaging metrics of white matter	5 cycles daily for 6 months	RIC improved cognitive function assessed by Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, Trail Making Test A and B and Judgment of Line Orientation	completed	[130]