Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial.
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ABSTRACT:
SUBMITTER: Godskesen LE
PROVIDER: S-EPMC7293253 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial.
Godskesen Line E LE Lassen Thomas R TR Jespersen Nichlas R NR Siersbæk Majken M Yan Yan Y Nielsen Michael M MM Tjønnfjord Sara K SK Grøntved Lars L Madsen Gunvor G Kjems Jørgen J Bøtker Hans E HE Schmidt Michael R MR Krag Aleksander A Kjeldsen Jens J
Scientific reports 20200612 1
Remote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RI ...[more]
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Project description:ImportanceDespite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke.ObjectiveTo evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke.Design, setting, and participantsThis was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023).InterventionThe intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants.Main outcomes and measuresThe primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke.ResultsAmong 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group.Conclusions and relevanceRIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke.Trial registrationClinicalTrials.gov Identifier: NCT03481777.
| S-EPMC10548297 | biostudies-literature
Project description:Background and Aim: Remote ischemic conditioning is a procedure purported to reduce the ischemic injury of an organ. This study aimed to explore the efficiency and safety of remote ischemic conditioning in patients with acute ischemic stroke. We hypothesized that remote ischemic conditioning administered from the first day of hospital admission would improve the infarct volume and clinical outcome at 180 days. Material and Methods: We performed a unicentric double-blind randomized controlled trial. We included all patients consecutively admitted to an Emergency Neurology Department with acute ischemic stroke, ineligible for reperfusion treatment, up to 24 hours from onset. All subjects were assigned to receive secondary stroke prevention treatment along with remote ischemic conditioning on the non-paretic upper limb during the first 5 days of hospitalization, twice daily - a blood pressure cuff placed around the arm was inflated to 20 mmHg above the systolic blood pressure (up to 180 mmHg) in the experimental group and 30 mmHg in the sham group. The primary outcome was the difference in infarct volume (measured on brain CT scan) at 180 days compared to baseline, whereas the secondary outcomes included differences in clinical scores (NIHSS, mRS, IADL, ADL) and cognitive/mood changes (MoCA, PHQ-9) at 180 days compared to baseline. Results: We enrolled 40 patients; the mean age was 65 years and 60% were men. Subjects in the interventional group had slightly better recovery in terms of disability, as demonstrated by the differences in disability scores between admission and 6 months (e.g., the median difference score for Barthel was -10 in the sham group and -17.5 in the interventional group, for ADL -2 in the sham group and -2.5 in the interventional group), as well as cognitive performance (the median difference score for MoCA was -2 in the sham group and -3 in the interventional group), but none of these differences reached statistical significance. The severity of symptoms (median difference score for NIHSS = 5 for both groups) and depression rate (median difference score for PHQ-9 = 0 for both groups) were similar in the two groups. The median difference between baseline infarct volume and final infarct volume at 6 months was slightly larger in the sham group compared to the interventional group (p = 0.4), probably due to an initial larger infarct volume in the former. Conclusion: Our results suggest that remote ischemic conditioning might improve disability and cognition. The difference between baseline infarct volume and final infarct volume at 180 days was slightly larger in the sham group.
| S-EPMC8435589 | biostudies-literature
Project description:In remote ischemic conditioning (RIC), brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue, or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical, or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1?, microribonucleic acid-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting, and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible, and inexpensive.
| S-EPMC4297315 | biostudies-other
Project description:Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC).This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score </=2), endoscopic remission, and quality of life were secondary outcomes.After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare.Rosiglitazone was efficacious in the treatment of mild to moderately active UC.
| S-EPMC2276587 | biostudies-literature
Project description:Background Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may protect the brain from ischemic reperfusion injury. Methods and Results We performed a phase IIb blinded dose-escalation sham-controlled trial in patients with hyperacute stroke, randomized 1:1 to receive RIC (four 5-minute cycles) or sham to the nonparetic upper limb, in 3 blocks of increasing dose, starting within 6 hours of ictus. The primary outcome was trial feasibility (recruitment, attrition). Secondary outcomes included adherence, tolerability, safety (serious adverse events), plasma biomarkers at days 1 and 4 (S100-ß protein, matrix metalloproteinase-9, and neuron-specific enolase), and functional outcome. Sixty participants were recruited from 2 centers (3 per month) with no loss to follow-up: time to randomization 4 hours 5 minutes (SD 72 minutes), age 72 years (12), men 60%, blood pressure 154/80 mm Hg (25/12), National Institutes of Health Stroke Scale 8.4 (6.9), and 55% thrombolyzed. RIC was well tolerated with adherence not differing between RIC and sham, falling in both groups on day 3 (P=0.001, repeated measures ANOVA) because of discharge or transfer. S100ß increased in the sham group (mean rise 111 pg/mL [302], P=0.041, repeated measures ANCOVA) but not the RIC group. There were no differences in matrix metalloproteinase-9, neuron-specific enolase, number with serious adverse events (RIC 10 versus sham 10, P=0.81), deaths (2 versus 4, P=0.36), or modified Rankin Scale score (2 [interquartile range 1-4], 2 [interquartile range, 1-3]; P=0.85). Conclusions RIC in hyperacute stroke is feasible when given twice daily for 2 days and appears safe in a small population with hyperacute stroke. A larger phase III trial is warranted. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02779712.
| S-EPMC6912955 | biostudies-literature
Project description:BackgroundRemote ischemic conditioning (RIC) is delivered by a blood pressure cuff over the limb, raising pressure 50 mmHg above the systolic blood pressure, to a maximum of 200 mmHg. The cuff is inflated for five minutes and then deflated for five minutes in a sequential ischemia-reperfusion cycle 4-5 times per session. Elevated pressure in the limb may be associated with discomfort and consequently reduced compliance. Continuous assessment of relative blood concentration and oxygenation with a tissue reflectance spectroscopy (a type of optical sensor device) placed over the forearm during the RIC sessions of the arm will allow us to observe the effect of inflation and deflation of the pressure cuff. We hypothesize, in patients with acute ischemic stroke (AIS) and small vessel disease, RIC delivered together with a tissue reflectance sensor will be feasible.MethodsThe study is a prospective, single-center, randomized control trial testing the feasibility of the device. Patients with AIS within 7 days from symptoms onset; who also have small vessel disease will be randomized 2:1 to intervention or sham control arms. All patients randomized to the intervention arm will receive 5 cycles of ischemia/reperfusion in the non-paralyzed upper limb with a tissue reflectance sensor and patients in the sham control arm will receive pressure by keeping the cuff pressure at 30 mmHg for 5 minutes. A total of 51 patients will be randomized, 17 in the sham control arm and 34 in the intervention arm. The primary outcome measure will be the feasibility of RIC delivered for 7 days or at the time of discharge. The secondary device-related outcome measures are fidelity of RIC delivery and the completion rate of intervention. The secondary clinical outcome includes a modified Rankin scale, recurrent stroke and cognitive assessment at 90 days.DiscussionRIC delivery together with a tissue reflectance sensor will allow insight into the blood concentration and blood oxygenation changes in the skin. This will allow individualized delivery of the RIC and improve compliance.Clinical trial registrationClinicalTrials.gov Identifier: NCT05408130, June 7, 2022.
| S-EPMC10159200 | biostudies-literature
Project description:BackgroundDespite the continuing effort in investigating the preventive therapies for stroke-associated pneumonia (SAP), which is closely associated with unfavorable outcomes, conclusively effective therapy for the prevention of SAP is still lacking. Remote ischemic conditioning (RIC) has been proven to improve the survival in the sepsis model and inflammatory responses have been indicated as important mechanisms involved in the multi-organ protection effect of RIC. This study aimed to assess the safety and the preliminary efficacy of RIC in the prevention of SAP in patients with acute ischemic stroke.MethodsWe performed a proof-of-concept, pilot open-label randomized controlled trial. Eligible patients (age > 18 years) within 48 h after stroke onset between March 2019 and October 2019 with acute ischemic stroke were randomly allocated (1:1) to the RIC group and the control group. All participants received standard medical therapy. Patients in the RIC group underwent RIC twice daily for 6 consecutive days. The safety outcome included any adverse events associated with RIC procedures. The efficacy outcome included the incidence of SAP, changes of immunological profiles including mHLA-DR, TLR-2, and TLR-4 as well as other plasma parameters from routine blood tests.ResultsIn total, 46 patients aged 63.1 ± 12.5 years, were recruited (23 in each group). Overall, 19 patients in the RIC group and 22 patients in the control group completed this study. No severe adverse event was attributed to RIC procedures. The incidence of SAP was lower in the remote ischemic conditioning group (2 patients [10.5%]) than that in the control group (6 patients [27.3%]), but no significant difference was detected in both univariate and multivariate analysis (p = 0.249 and adjusted p = 0.666). No significance has been found in this pilot trial in the level of immunological profiles HLA-DR, TLR4 and TLR2 expressed on monocytes as well as blood parameters tested through routine blood tests between the two groups (p > 0.05). The IL-6 and IL-1β levels at day 5 after admission in the RIC group were lower than those in the control group (p < 0.05).InterpretationThis proof-of-concept pilot randomized controlled trial was to investigate RIC as a prevention method for SAP. Remote ischemic conditioning is safe in the prevention of SAP in patients with acute ischemic stroke. The preventive effect of RIC on SAP should be further validated in future studies.
| S-EPMC8850400 | biostudies-literature
Project description:BackgroundSeptic shock is a major public health problem that is associated with up to 50% mortality. Unfavorable outcomes are mainly attributed to multiple organ failure (MOF) resulting from an uncontrolled inflammatory response and ischemia-reperfusion processes. REmote ischemic COnditioning (RECO) is a promising intervention to prevent ischemia-reperfusion injury. We hypothesize that RECO would reduce the severity of septic shock-induced MOF.Methods/designRECO in septic shock patients (RECO-Sepsis study) is an ongoing, prospective, multicenter, randomized, open-label trial, testing whether RECO, as an adjuvant therapy to conventional treatment in septic shock, decreases the severity of MOF as assessed by the Sequential Organ Failure Assessment (SOFA) score. Adult patients admitted to an intensive care unit with documented or suspected infection, lactatemia > 2 mmol/l, and treated with norepinephrine for less than 12 h are potentially eligible for the study. Non-inclusion criteria are: having expressed the wish not to be resuscitated, contraindication for the use of a brachial cuff on both arms, intercurrent disease with an expected life expectancy of less than 24 h, cardiac arrest, and pregnant or breastfeeding women. After enrollment, patients are randomized (n = 180) 1:1 to receive RECO or no adjunctive intervention. RECO consists of four cycles of cuff inflation to 200 mmHg for 5 min and then deflation to 0 mmHg for another 5 min. RECO is performed at inclusion and repeated 12 and 24 h later. The primary endpoint is the mean daily SOFA score up to day 4 after inclusion. Secondary outcomes include the need for organ support, hospital length of stay, and 90-day mortality.DiscussionResults of this proof-of-concept trial should provide information on the efficacy of RECO in patients with septic shock.Trial registrationClinicalTrials.gov, ID: identifier: NCT03201575 . Registered on 28 June 2017.
| S-EPMC6532140 | biostudies-literature
Project description:ImportanceOlamkicept, a soluble gp130-Fc-fusion-protein, selectively inhibits interleukin 6 (IL-6) trans-signaling by binding the soluble IL-6 receptor/IL-6 complex. It has anti-inflammatory activities in inflammatory murine models without immune suppression.ObjectiveTo assess the effect of olamkicept as induction therapy in patients with active ulcerative colitis.Design, setting, and participantsRandomized, double-blind, placebo-controlled phase 2 trial of olamkicept in 91 adults with active ulcerative colitis (full Mayo score ≥5, rectal bleeding score ≥1, endoscopy score ≥2) and an inadequate response to conventional therapy. The study was conducted at 22 clinical study sites in East Asia. Patients were recruited beginning in February 2018. Final follow-up occurred in December 2020.InterventionsEligible patients were randomized 1:1:1 to receive a biweekly intravenous infusion of olamkicept 600 mg (n = 30) or 300 mg (n = 31) or placebo (n = 30) for 12 weeks.Main outcomes and measuresThe primary end point was clinical response at week 12 (defined as ≥3 and ≥30% decrease from baseline total Mayo score; range, 0-12 [worst] with ≥1 decrease and ≤1 in rectal bleeding [range, 0-3 {worst}]). There were 25 secondary efficacy outcomes, including clinical remission and mucosal healing at week 12.ResultsNinety-one patients (mean age, 41 years; 25 women [27.5%]) were randomized; 79 (86.8%) completed the trial. At week 12, more patients receiving olamkicept 600 mg (17/29 [58.6%]) or 300 mg (13/30 [43.3%]) achieved clinical response than placebo (10/29 [34.5%]), with adjusted difference vs placebo of 26.6% (90% CI, 6.2% to 47.1%; P = .03) for 600 mg and 8.3% (90% CI, -12.6% to 29.1%; P = .52) for 300 mg. Among patients randomized to receive 600 mg olamkicept, 16 of 25 secondary outcomes were statistically significant compared with placebo. Among patients randomized to receive 300 mg, 6 of 25 secondary outcomes were statistically significant compared with placebo. Treatment-related adverse events occurred in 53.3% (16/30) of patients receiving 600 mg olamkicept, 58.1% (18/31) receiving 300 mg olamkicept, and 50% (15/30) receiving placebo. The most common drug-related adverse events were bilirubin presence in the urine, hyperuricemia, and increased aspartate aminotransferase levels, and all were more common in the olamkicept groups compared with placebo.Conclusions and relevanceAmong patients with active ulcerative colitis, biweekly infusion of olamkicept 600 mg, but not 300 mg, resulted in a greater likelihood of clinical response at 12 weeks compared with placebo. Further research is needed for replication and to assess longer-term efficacy and safety.Trial registrationClinicalTrials.gov Identifier: NCT03235752.
| S-EPMC9993185 | biostudies-literature
Project description:BackgroundAcute ischemic stroke (AIS) complicating an acute myocardial infarction (AMI) is not uncommon, but can severely worsen the clinical prognosis. This study aimed to investigate whether remote ischemic conditioning (RIC) could provide clinical benefits to patients with AIS complicating AMI.MethodsSubjects with AIS complicating AMI were recruited in this double-blind, randomized, controlled trial; assigned to the RIC and sham groups; and respectively underwent twice daily RIC and sham RIC for 2 weeks. All subjects received standard medical therapy. The primary endpoint was the rate of major adverse cardiac and cerebrovascular events (MACCEs) within 3 months after enrollment. MACCEs comprise of death from all causes, unstable anginas, AMI, acute ischemic strokes, and transient ischemic attacks.ResultsEighty subjects were randomly assigned; 37 patients in the RIC group and 40 patients in the sham-RIC group completed the 3-month follow-up and were included in the final analysis. Both RIC and sham RIC procedures were well tolerated. At 3-month follow-up, 11 subjects (29.7%) in the RIC group experienced MACCEs compared to 21 (52.5%) in the sham group (hazard ratio [HR], 0.396; 95% confidence interval, 0.187-0.838; adjusted p < 0.05). Six subjects (16.2%) in the RIC group had died at the 3-month follow up, significantly lower than the 15 (37.5%) deaths in the sham group (adjusted HR 0.333; 95% CI 0.126-0.881; p = 0.027). Seventeen subjects (45.9%) in the RIC group and 6 subjects (15.0%) in the sham group achieved functional independence (mRS score ≤ 2) at 3-month follow-up (adjusted OR 12.75; 95% CI 2.104-77.21; p = 0.006).ConclusionsAmong patients with acute ischemic stroke complicating acute myocardial infarction, treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days.Trial registrationURL: www.Clinicaltrialsgov . Unique identifier: NCT03868007. Registered 8 March 2019.
| S-EPMC10759604 | biostudies-literature