STROKE34 Study Protocol: A Randomized Controlled Phase IIa Trial of Intra-Arterial CD34+ Cells in Acute Ischemic Stroke

Abstract

Rationale/aimDespite the increasing efficacy of recanalization therapies for acute ischemic stroke, a large number of patients are left with long-term functional impairment, devoid of efficacious treatments. CD34+ cells comprise a subset of bone marrow-derived mononuclear cells with the capacity to promote angiogenesis in ischemic lesions and have shown promising results in observational and in vitro studies. In this study, we aim to assess the efficacy of an autotransplant of CD34+ cells in acute ischemic stroke.Sample size estimates30 patients will be randomized for a power of 90% and alpha of 0.05 to detect a difference in 3 months infarct volume.Methods and designWe will screen 18–80 years old patients with acute ischemic stroke due to occlusion of a middle cerebral artery (MCA) for randomization. Persistent arterial occlusions, contra-indications to magnetic resonance imaging (MRI), premorbid dependency, or other severe diseases will be excluded. Treatment will involve bone marrow aspiration, selection of CD34+ cells, and their administration intra-arterially in the symptomatic MCA by angiography. Patients will be randomized for treatment at 7 (±2) days, 20 (±5 days) or sham procedure, 10 in each group.Study outcomesThe primary outcome will be infarct volume in MRI performed at 3 months. Secondary outcomes will include adverse events and multidimensional functional and neurological measures.Discussion/conclusionSTROKE34 is a PROBE design phase IIa clinical trial to assess the efficacy of intra-arterial administration of CD34+ cells 7 and 20 days after acute ischemic stroke.Trial registration (EU Clinical Trials Register)2017-002456-88.

A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation

“…Cell therapies using either bone marrow mononuclear cells 1 , or bone marrow-derived mesenchymal stem/stromal cells 2–4 was proposed as a therapeutic approach targeting multiple cell types to enhance protection and recovery via pleiotropic mechanisms after ischemic stroke 5 . These days, clinical application towards further development of cell therapies against ischemic stroke are accelerated.…”

Angiogenic CD34 Stem Cell Therapy in Coronary Microvascular Repair—A Systematic Review

“…Although the majority of the clinical trials have been in patients with no-option refractory angina [ 15 , 16 , 17 , 18 , 19 ], CD34 + stem cells have also been investigated in clinical studies for peripheral ischemia [ 31 , 32 ], nonischemic cardiomyopathy [ 33 ], myocardial infarction [ 20 ], and ischemic stroke [ 34 , 35 ].…”

“…All patients had clinical improvement as assessed by modified Rankin score (median score: 4 to 2) and National Institutes of Health Stroke Scale (median score: 9 to 2) at 6 months with no significant adverse events, thus establishing preliminary safety and feasibility. Furthermore, the ongoing STROKE34 trial is a randomized, placebo-controlled, phase 2a trial using CD34 + stem cells in patients with acute ischemic stroke due to occlusion of the middle cerebral artery [ 35 ].…”

Aging and Neurodegenerative Disease: Is the Adaptive Immune System a Friend or Foe?

“…Treatment with IL-10, on the other hand, reduced TNF-α and IFN-γ cytokine overexpression and prevented secondary infarct progression ( Liesz et al, 2009 ). Additionally, administration of CD34 + immune progenitor cells, which can differentiate into both innate and adaptive immune cells, promoted revascularisation and enhanced neurogenesis after MCAO induction ( Taguchi et al, 2004 ), being now further evaluated in clinical trials ( Sargento-Freitas et al, 2018 ). Although these studies highlight the ability of adaptive immune cells to reduce neurodegeneration, it can be difficult to establish whether these effects are through neuroprotection or by promoting neuroregeneration and plasticity.…”