Dataset Information

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.

ABSTRACT: To determine if chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623). This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multi-center trial (N = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (N = 61), and efficacy in the modified intent-to-treat population of randomized patients who underwent surgery (N = 61; SB623 = 46, control = 15). The primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (LS mean [SE]) +8.3 (1.4) vs +2.3 (2.5) for control at 6 months, the LS mean difference was 6.0 (95% CI: 0.3-11.8); p = 0.040. Secondary efficacy endpoints improved from baseline, but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25). SB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls. This study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.

SUBMITTER: Kawabori M

PROVIDER: S-EPMC8055341 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.

Kawabori Masahito M Weintraub Alan H AH Imai Hideaki H Zinkevych Iaroslav I McAllister Peter P Steinberg Gary K GK Frishberg Benjamin M BM Yasuhara Takao T Chen Jefferson W JW Cramer Steven C SC Achrol Achal S AS Schwartz Neil E NE Suenaga Jun J Lu Daniel C DC Semeniv Ihor I Nakamura Hajime H Kondziolka Douglas D Chida Dai D Kaneko Takehiko T Karasawa Yasuaki Y Paadre Susan S Nejadnik Bijan B Bates Damien D Stonehouse Anthony H AH Richardson R Mark RM Okonkwo David O DO

Neurology 20210222 8

<h4>Objective</h4>To determine whether chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623).<h4>Methods</h4>This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 Stem Cell Therapy for Traumatic Brain Injury (STEMTRA) trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in ...[more]

PMID: 33397772

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Project description:BackgroundApproaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.Methods and findingsForty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.ConclusionCycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted.

Project description:BackgroundCombination therapies delivered remotely via the internet or mobile devices are increasingly being used to improve and promote the self-management of chronic conditions. However, little is known regarding the long-term effects of these interventions.ObjectiveThe aim of this study is to evaluate the effectiveness of a multimodal intervention program that measures associated variables such as catastrophizing, pain acceptance, and quality of life using a mobile device in people with chronic pain in an outpatient setting.MethodsA randomized controlled clinical trial was performed using parallel treatment groups. A total of 209 patients with chronic musculoskeletal pain were randomly assigned to one of the two study arms. The intervention group received a standard web-based psychosocial therapy-type program of activities through a smartphone for 6 weeks. The control group only had access to the Find out more section of the app, which contained audiovisual material for pain management based on a self-help approach. The primary outcome was catastrophizing measured using the Pain Catastrophizing Scale (PCS). Secondary outcomes were pain acceptance measured using the Chronic Pain Acceptance Questionnaire and health-related quality of life measured using the EuroQol Visual Analogue Scale. Assessments were conducted at baseline (T1), after treatment (T2), and at the 3-month follow-up (T3). The variations between the different phases were assessed using the percentage change rescaled with log base 2. The Cohen d was calculated based on the results of the linear mixed model. The investigators of the study who evaluated the results were not involved in patient recruitment and were blinded to the group assignment.ResultsPositive effects were found in the intervention group (T2-T1) in catastrophizing between the baseline and posttreatment phases (P<.001) and in helplessness (-0.72 vs 0.1; P=.002), rumination (-1.59 vs -0.53; P<.001), acceptance (0.38 vs 0.05; P=.001), and quality of life (0.43 vs -0.01; P=.002), although no significant changes were found for magnification (0.2 vs 0.77; P=.14) and satisfaction with health (0.25 vs -0.27; P=.13). Three months after treatment, significant differences were observed in the intervention group for the outcome variable of catastrophizing (PCS; -0.59 vs 0.2; P=.006) and the PCS subscales of helplessness (-0.65 vs 0.01; P=.07), rumination (1.23 vs -0.59; P=.04), and magnification (0.1 vs 0.86; P=.02).ConclusionsThe results of our study suggest that app-based mobile multidimensional treatments for adults with chronic pain improve catastrophizing, quality of life, and psychological flexibility immediately after treatment and that the effects are maintained for the primary outcome of catastrophizing for at least 3 months following treatment. Moreover, they promote self-management and can be used to complement face-to-face pain treatments.Trial registrationClinicalTrials.gov NCT04509154; https://clinicaltrials.gov/ct2/show/NCT04509154.

Project description:BackgroundImplantation failure is the main factor affecting the success rate of in vitro fertilization (IVF) procedures. Studies have reported that uterine contractions (UC) at the time of embryo transfer (ET) were inversely related to implantation and pregnancy rate, hence reducing the success of IVF treatments. Various pharmacological agents, with the exception of calcium channel blockers, have been investigated to improve ET outcomes by reducing UC. Thus, a double-blinded randomized, placebo-controlled trial was conducted to determine whether nifedipine, a calcium channel blocker with potent smooth muscle relaxing activity and an excellent safety profile, can improve the outcome of patients undergoing ET treatments.MethodsNinety-three infertile women were recruited into 1 of 2 groups: placebo (n = 47) or nifedipine 20 mg (n = 46). Study participants were admitted 30 minutes prior to ET and given either tablet after their baseline vital signs were recorded. They then underwent ET and were observed for adverse events for another 30 minutes post-ET. Follow up of the participants' outcomes was conducted via electronic medical records. The primary outcomes are implantation and clinical pregnancy rates. Secondary outcomes include any maternal or fetal adverse events, miscarriage, pregnancy, live births, and neonatal outcomes. Resulting data were then analyzed using t test, Pearson chi-square test, and Fisher exact test to compare outcomes between the 2 groups.ResultsNo statistical differences in the implantation rate (42.6% vs 39.1%, P = .737, rate ratio 0.868, 95% confidence interval [CI]: 0.379-1.986) and the clinical pregnancy rate (23.4% vs 26.1%, P = .764, rate ratio 1.155, 95% CI: 0.450-2.966) were detected between the placebo and the treatment groups. In addition, no statistical significance between the placebo and the treatment groups for any secondary outcomes were detected.ConclusionsThis double blinded, randomized, and placebo-controlled trial demonstrated that the single use of 20 mg nifedipine given 30 minutes before embryo transfer did not improve the implantation rate or the clinical pregnancy rate of the infertility treatment. Further studies are required to demonstrate the clinical benefits and risks of nifedipine usage in embryo transfer.

Project description:BackgroundChronic shoulder pain (CSP) is a common condition with various etiologies, including rotator cuff disorders, adhesive capsulitis, shoulder instability, and shoulder arthritis. It is associated with substantial disability and psychological distress, resulting in poor productivity and quality of life. Physical therapy constitutes the mainstay treatment for CSP, but several barriers exist in accessing care. In recent years, telerehabilitation has gained momentum as a potential solution to overcome such barriers. It has shown numerous benefits, including improving access and convenience, promoting patient adherence, and reducing costs. However, to date, no previous randomized controlled trial has compared fully remote digital physical therapy to in-person rehabilitation for nonoperative CSP.ObjectiveThe aim of this study is to compare clinical outcomes between digital physical therapy and conventional in-person physical therapy in patients with CSP.MethodsWe conducted a single-center, parallel-group, randomized controlled trial involving 82 patients with CSP referred for outpatient physical therapy. Participants were randomized into digital or conventional physical therapy (8-week interventions). The digital intervention consisted of home exercise, education, and cognitive behavioral therapy (CBT), using a device with movement digitalization for biofeedback and asynchronous physical therapist monitoring through a cloud-based portal. The conventional group received in-person physical therapy, including exercises, manual therapy, education, and CBT. The primary outcome was the change (baseline to 8 weeks) in function and symptoms using the short-form of Disabilities of the Arm, Shoulder, and Hand questionnaire. Secondary outcome measures included self-reported pain, surgery intent, analgesic intake, mental health, engagement, and satisfaction. All questionnaires were delivered electronically.ResultsA total of 90 participants were randomized into digital or conventional physical therapy, with 82 receiving the allocated intervention. Both groups experienced significant improvements in function measured by the short-form of the Disabilities of the Arm, Shoulder, and Hand questionnaire, with no differences between groups (-1.8, 95% CI -13.5 to 9.8; P=.75). For secondary outcomes, no differences were observed in surgery intent, analgesic intake, and mental health or worst pain. Higher reductions were observed in average and least pain in the conventional group, which, given the small effect sizes (least pain 0.15 and average pain 0.16), are unlikely to be clinically meaningful. High adherence and satisfaction were observed in both groups, with no adverse events.ConclusionsThis study shows that fully remote digital programs can be viable care delivery models for CSP given their scalability and effectiveness, assessed through comparison with high-dosage in-person rehabilitation.Trial registrationClinicalTrials.gov (NCT04636528); https://clinicaltrials.gov/study/NCT04636528.

Dataset Information

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.

Publications

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial.

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