scholarly journals Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans

2021 ◽  
Vol 118 (39) ◽  
pp. e2026676118
Author(s):  
Alexander W. Dromerick ◽  
Shashwati Geed ◽  
Jessica Barth ◽  
Kathaleen Brady ◽  
Margot L. Giannetti ◽  
...  
Keyword(s):  
Human Brain ◽  
Controlled Trial ◽  
Primary Outcome Measure ◽  
Essential Elements ◽  
Motor Recovery ◽  
Stroke Recovery ◽  
Sensitive Period ◽  
Optimal Time ◽  
Motor Training ◽  
Acute Group

Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at ≤30 d (acute), 2 to 3 mo (subacute), or ≥6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 ± 2.63,P= 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 ± 2.59 points,P= 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 ± 2.25,P= 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans.

scholarly journals Randomized controlled trial of convalescent plasma therapy against standard therapy in patients with severe COVID-19 disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manaf AlQahtani ◽  
Abdulkarim Abdulrahman ◽  
Abdulrahman Almadani ◽  
Salman Yousif Alali ◽  
Alaa Mahmood Al Zamrooni ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Severe Disease ◽  
Pilot Trial ◽  
Standard Of Care ◽  
Primary Outcome Measure ◽  
Secondary Outcome ◽  
Open Label ◽  
Plasma Therapy

AbstractConvalescent plasma (CP) therapy in COVID-19 disease may improve clinical outcome in severe disease. This pilot study was undertaken to inform feasibility and safety of further definitive studies. This was a prospective, interventional and randomized open label pilot trial in patients with severe COVID-19. Twenty COVID-19 patients received two 200 ml transfusions of convalescent patient CP over 24-h compared with 20 who received standard of care. The primary outcome was the requirement for ventilation (non-invasive or mechanical ventilation). The secondary outcomes were biochemical parameters and mortality at 28 days. The CP group were a higher risk group with higher ferritin levels (p < 0.05) though respiratory indices did not differ. The primary outcome measure was required in 6 controls and 4 patients on CP (risk ratio 0.67, 95% CI 0.22–2.0, p = 0.72); mean time on ventilation (NIV or MV) did not differ. There were no differences in secondary measures at the end of the study. Two patients died in the control and one patient in the CP arm. There were no significant differences in the primary or secondary outcome measures between CP and standard therapy, although a larger definitive study is needed for confirmation. However, the study did show that CP therapy appears to be safe in hospitalized COVID-19 patients with hypoxia.Clinical trials registration NCT04356534: 22/04/2020.

scholarly journals Computerised cognitive–behavioural therapy for adults with intellectual disability: randomised controlled trial

2017 ◽  
Vol 211 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Patricia Cooney ◽  
Catherine Jackman ◽  
David Coyle ◽  
Gary O'Reilly
Keyword(s):  
Intellectual Disability ◽  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Controlled Trial ◽  
Behavioural Therapy ◽  
Primary Outcome Measure ◽  
Cognitive Behavioural ◽  
Randomised Controlled

BackgroundDespite the evidence base for computer-assisted cognitive–behavioural therapy (CBT) in the general population, it has not yet been adapted for use with adults who have an intellectual disability.AimsTo evaluate the utility of a CBT computer game for adults who have an intellectual disability.MethodA 2 × 3 (group × time) randomised controlled trial design was used. Fifty-two adults with mild to moderate intellectual disability and anxiety or depression were randomly allocated to two groups: computerised CBT (cCBT) or psychiatric treatment as usual (TAU), and assessed at pre-treatment, post-treatment and 3-month follow-up. Forty-nine participants were included in the final analysis.ResultsA significant group x time interaction was observed on the primary outcome measure of anxiety (Glasgow Anxiety Scale for people with an Intellectual Disability), favouring cCBT over TAU, but not on the primary outcome measure of depression (Glasgow Depression Scale for people with a Learning Disability). A medium effect size for anxiety symptoms was observed at post-treatment and a large effect size was observed after follow-up. Reliability of Change Indices indicated that the intervention produced clinically significant change in the cCBT group in comparison with TAU.ConclusionsAs the first application of cCBT for adults with intellectual disability, this intervention appears to be a useful treatment option to reduce anxiety symptoms in this population.

Abstract 8: A Phase IIb Double-blind, Randomized, Placebo Controlled Study of GSK249320 for Stroke Recovery

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Steven C Cramer ◽  
Lori A Enney ◽  
Colleen K Russell ◽  
Monica Simeoni ◽  
Thomas R Thompson
Keyword(s):  
Monoclonal Antibody ◽  
Substantial Reduction ◽  
Indirect Evidence ◽  
Primary Outcome Measure ◽  
Clinical Findings ◽  
Stroke Recovery ◽  
Gait Velocity ◽  
Controlled Study ◽  
Double Blind ◽  
Target Binding

Introduction: One class of potential post-stroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein (MAG). The aim of the current study was to extend preclinical and clinical findings of GSK249320, an IgG1-type monoclonal antibody to MAG, to explore effects on motor outcomes after stroke. Methods: This was a phase IIb double-blind, randomized, placebo controlled study (GSK funded; clinicaltrials.gov # NCT01808261). At 30 international sites, patients with ischemic stroke 24-72 hours prior and deficits in gait were randomized to two IV infusions of GSK249320 or placebo. Primary outcome measure was change in gait velocity from baseline to Day 90. Results: A total of 134 subjects were randomized. The two groups were overall well matched at baseline. The study was stopped at the pre-specified interim analysis because the treatment difference met the predefined futility criteria cutoff. Secondary endpoints, including gait analyzed categorically and upper extremity function (Box & Blocks score), were concordant. The two IV infusions of GSK249320 were well tolerated. Although direct evidence that the therapy reached the biological target was not available, indirect evidence of target binding was suggested by the substantial reduction in free MAG plasma levels with GSK249320 treatment. Conclusions: The monoclonal antibody GSK249320 administered IV within 72 hours of stroke onset demonstrated no improvement in gait velocity as compared to placebo. The antibody was well tolerated and showed low immunogenicity, findings that may prove useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways in order to improve recovery from stroke.

scholarly journals 2190 Longitudinal changes in EEG power envelope connectivity are proportional to motor recovery in chronic stroke patients

2018 ◽  
Vol 2 (S1) ◽  
pp. 17-17
Author(s):  
Joseph B. Humphries ◽  
David T. Bundy ◽  
Eric C. Leuthardt ◽  
Thy N. Huskey
Keyword(s):  
Motor Cortex ◽  
Motor Imagery ◽  
Stroke Rehabilitation ◽  
Brain Computer Interface ◽  
Chronic Stroke ◽  
Motor Recovery ◽  
Stroke Recovery ◽  
Computer Interface ◽  
Beta Band ◽  
Stroke Patients

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to determine the degree to which the use of a contralesionally-controlled brain-computer interface for stroke rehabilitation drives change in interhemispheric motor cortical activity. METHODS/STUDY POPULATION: Ten chronic stroke patients were trained in the use of a brain-computer interface device for stroke recovery. Patients perform motor imagery to control the opening and closing of a motorized hand orthosis. This device was sent home with patients for 12 weeks, and patients were asked to use the device 1 hour per day, 5 days per week. The Action Research Arm Test (ARAT) was performed at 2-week intervals to assess motor function improvement. Before the active motor imagery task, patients were asked to quietly rest for 90 seconds before the task to calibrate recording equipment. EEG signals were acquired from 2 electrodes—one each centered over left and right primary motor cortex. Signals were preprocessed with a 60 Hz notch filter for environmental noise and referenced to the common average. Power envelopes for 1 Hz frequency bands (1–30 Hz) were calculated through Gabor wavelet convolution. Correlations between electrodes were then calculated for each frequency envelope on the first and last 5 runs, thus generating one correlation value per subject, per run. The chosen runs approximately correspond to the first and last week of device usage. These correlations were Fisher Z-transformed for comparison. The first and last 5 run correlations were averaged separately to estimate baseline and final correlation values. A difference was then calculated between these averages to determine correlation change for each frequency. The relationship between beta-band correlation changes (13–30 Hz) and the change in ARAT score was determined by calculating a Pearson correlation. RESULTS/ANTICIPATED RESULTS: Beta-band inter-electrode correlations tended to decrease more in patients achieving greater motor recovery (Pearson’s r=−0.68, p=0.031). A similar but less dramatic effect was observed with alpha-band (8–12 Hz) correlation changes (Pearson’s r=−0.42, p=0.22). DISCUSSION/SIGNIFICANCE OF IMPACT: The negative correlation between inter-electrode power envelope correlations in the beta frequency band and motor recovery indicates that activity in the motor cortex on each hemisphere may become more independent during recovery. The role of the unaffected hemisphere in stroke recovery is currently under debate; there is conflicting evidence regarding whether it supports or inhibits the lesioned hemisphere. These findings may support the notion of interhemispheric inhibition, as we observe less in common between activity in the 2 hemispheres in patients successfully achieving recovery. Future neuroimaging studies with greater spatial resolution than available with EEG will shed further light on changes in interhemispheric communication that occur during stroke rehabilitation.

scholarly journals Randomised Double-Blind Trial of Combination Antibiotic Therapy in Rheumatoid Arthritis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Angela Smith ◽  
Caroline Doré ◽  
Peter Charles ◽  
Alena Vallance ◽  
Tara Potier ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Placebo Group ◽  
Active Treatment ◽  
Active Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Primary Outcome Measure ◽  
Good Evidence ◽  
Double Blind ◽  
Acr20 Response ◽  
Significant Difference

Objective. A combination of intravenous clindamycin and oral tetracycline has been used for many years as a treatment for active rheumatoid arthritis (RA), despite the absence of good evidence for its efficacy. A single-blind pilot study of this therapy suggested that a double-blind placebo-controlled trial was warranted.Methods. Patients with active RA were randomised in a 2 : 1 ratio to receive active treatment or placebo for 25 weeks. The active treatment consisted of intravenous clindamycin in a reducing regime, and oral tetracycline twice daily three times a week. 50 patients were to be recruited. The primary outcome measure was the proportion of patients achieving an ACR20 response.Results. An interim statistical analysis was performed after 20 patients had completed the study. Two patients in the active group achieved an ACR20 response, with none in the placebo group (NS). There was a better ESR20 response in the placebo group (P=.02). There were no other significant differences between the groups. The results indicated that it was unlikely that a significant difference in ACR20 response would emerge if the remaining 30 patients were recruited. The trial was therefore halted.Conclusion. This antibiotic regime is unlikely to be a valuable therapy for active rheumatoid arthritis.

scholarly journals Effects of Deqi on Autonomic Balance in Adult Tinnitus Patients: Study Design of a Randomized Controlled Trial

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Qian-Qian Li ◽  
Guang-Xia Shi ◽  
Xin-Xing Fu ◽  
Li-Li Han ◽  
Li-Ying Liu ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Controlled Trial ◽  
Primary Outcome Measure ◽  
Autonomic Nervous ◽  
Nervous System Function ◽  
Acupuncture Effect ◽  
Randomised Controlled

Background. Recent reports suggest that a proportion of tinnitus patients suffer from mental illness. Autonomic nervous system plays a useful role in tinnitus therapy since electrical vagal nerve stimulation (VNS) has been frequently used to alleviate tinnitus-induced depression in clinic. heart rate variability (HRV), which is reflective of autonomic nervous system function, has been proved to be modulated by acupuncture. In the present study, we aim to compare the effect of deqi sensation on heart rate variability in adult tinnitus patients.Methods. Thirty participants are randomly assigned to verum acupuncture (creating deqi) or shallow acupuncture (not creating deqi) at Baihui (Du-20), Shenting (Du-24), Tinghui (GB-2), Waiguan (SJ-5), and Zulinqi (GB-41) for 3 weeks. The primary outcome measure is heart rate variability, which is measured at the first acupuncture, as well as the last acupuncture.Discussion. Completion of this trial will help to identify the role of deqi sensation in acupuncture effect for tinnitus and reveal an autonomic modulation mechanism for acupuncture effect.Trial Registration. This trial is registered with International Standard Randomised Controlled Trial NumberISRCTN58013563.

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