scholarly journals fMRI as an outcome measure in clinical trials: A systematic review in clinicaltrials.gov

2019 ◽  
Author(s):  
Alaleh Sadraee ◽  
Martin P. Paulus ◽  
Hamed Ekhtiari
Keyword(s):  
Clinical Trials ◽  
Pain Perception ◽  
Outcome Measure ◽  
Cue Reactivity ◽  
Region Of Interest ◽  
Link Type ◽  
Sensorimotor Systems ◽  
Monetary Incentive Delay ◽  
Positive Valence ◽  
Validation Of Results

AbstractBackgroundFunctional magnetic resonance imaging (fMRI) is quickly becoming a significant outcome measure for clinical trials and as more than one thousand trials with fMRI as an outcome measure were registered in clinicaltrials.gov at the time of writing this article. However, 93% of these registered trials are still not completed with published results and there is no picture available about methodological dimensions of these ongoing trials with fMRI as an outcome measure.MethodsWe collected trials that use fMRI as an outcome measure by searching “fMRI” in the ClinicalTrials.gov registry on October 13 2018 and reviewing each trial’s record entry. Eligible trials’ characteristics were extracted and summarized.ResultsIn total, 1386 clinical trials were identified that reported fMRI in their outcome measures with fMRI as the only primary outcome in 33% of them. 82% of fMRI trials were started after 2011. The most frequent intervention was drug (29%). 57% of trials had parallel assignment design and 20% were designed for cross over assignment. For task-based fMRI, cognitive systems (46%) based on RDoC was the most frequent domain of tasks, followed by positive valence systems (19%), systems for social processing (10%) and sensorimotor systems (5%). Less than one-third of trials (28%) registered at least one region of interest for their analysis. Food cue reactivity task, pain perception task, n-back task and monetary incentive delay task were recruited in more than 25 registered trials.ConclusionThe number of fMRI trials (fMRI as an outcome measure) with both task and rest protocols is growing rapidly. Different RDoC domains are covered by various tasks in fMRI trials. However, our study suggests the need of greater harmony and better standardization for registration of fMRI details on both methods and analysis which would allow for more effective comparison across studies in systematic reviews and also help the validation of results towards having fMRI as a biomarker in the future.

scholarly journals Effect of Tai Chi Training on Plantar Loads during Walking in Individuals with Knee Osteoarthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Zhiwang Zhang ◽  
Lingyan Huang ◽  
Yu Liu ◽  
Lin Wang
Keyword(s):  
Clinical Trials ◽  
Knee Osteoarthritis ◽  
Education Program ◽  
Tai Chi ◽  
Peak Pressure ◽  
Maximum Force ◽  
Control Group ◽  
Link Type ◽  
Wellness Education ◽  
Metatarsophalangeal Joints

Tai Chi is an available method for the treatment of knee osteoarthritis (KOA). The impacts of Tai Chi on plantar loads of individuals with KOA are not fully understood. 46 participants with knee osteoarthritis were randomly assigned into the Tai Chi group (n=23) or the control group (n=23). The Tai Chi group attended a 6-month Tai Chi program, and the control group participated in a wellness education program. Novel Pedar-X system was used to collect the peak pressure (PP) and maximum force (MF) during walking before and 6 months after the intervention. Significant higher peak pressure and maximum force were observed in the 4th and 5th metatarsophalangeal joints in the Tai Chi group. However, there were significant declines in the peak pressure of the whole foot and the 2nd and 3rd metatarsophalangeal joints and maximum force of the heel in the control group. These results suggested that individuals with KOA might change the pattern of plantar loads during walking through Tai Chi, and plantar loads would be useful as a parameter to assess the effect of Tai Chi on knee osteoarthritis. This trial is registered with Clinical Trials: CHiCTR-TRC-13003264.

scholarly journals Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e041463
Author(s):  
Anita Mansouri ◽  
Naomi McGregor ◽  
Rachel Dunn ◽  
Sam Dobbie ◽  
Jane Holmes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Antiangiogenic Therapy ◽  
Single Agent ◽  
Unmet Need ◽  
Dropout Rate ◽  
Weekly Paclitaxel ◽  
Type I ◽  
Link Type ◽  
Platinum Based Chemotherapy

IntroductionPatients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months.Methods and analysisEthics and disseminationThis study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150.Trial registration numberISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.

scholarly journals SAT0121 PAIN AND OTHER PATIENT-REPORTED OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO DID OR DID NOT ACHIEVE TREATMENT RESPONSE BASED ON IMPROVEMENT IN SWOLLEN JOINTS IN TOCILIZUMAB CLINICAL TRIALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 994.2-995
Author(s):  
A. Sebba ◽  
J. Han ◽  
S. Mohan
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Pain Score ◽  
Patient Reported Outcomes ◽  
Component Score ◽  
Link Type ◽  
Pain Scores ◽  
Sf 36 ◽  
Patient Reported ◽  
Nonresponder Group

Background:Significant improvements in pain and other patient-reported outcomes (PROs) have been shown in large clinical trials in patients with rheumatoid arthritis (RA) who receive tocilizumab (TCZ) compared with placebo (PBO). Recent data suggest that pain in RA may be noninflammatory as well as inflammatory, and improvement in pain scores and other PROs may be seen in patients who do not respond to treatment based on disease activity measures that evaluate inflammation.Objectives:To assess changes in pain scores and other PROs in patients with RA who did or did not achieve ≥ 20% improvement in SJC in TCZ clinical trials.Methods:Data from patients with active RA who received intravenous TCZ 8 mg/kg + MTX or PBO + MTX in 3 Phase III studies (OPTION [NCT00106548], TOWARD [NCT00106574] and LITHE [NCT00109408]) were included. All patients had moderate to severe RA with an inadequate response or intolerance of MTX (OPTION, LITHE) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs; TOWARD). Changes in pain (visual analog scale [VAS], 0-100 mm), Health Assessment Questionnaire Disability Index (HAQ-DI, 0-3), 36-Item Short Form Survey (SF-36) physical component score (PCS) and mental component score (MCS; 0-50) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score (0-52) from baseline to Week 24 were evaluated. Results were compared between patients receiving TCZ + MTX and those receiving PBO + MTX in both patients who achieved ≥ 20% improvement in SJC (responders) and those who did not (nonresponders). The changes from baseline were analyzed using a mixed model with repeated measures, including the following covariates and interactions: treatment, visit, baseline of endpoint, region, baseline DAS28 and interactions of visit with treatment and baseline of endpoint.Results:Data from 1254 responders (TCZ + MTX, n = 831; PBO + MTX, n = 423) and 620 nonresponders (TCZ + MTX, n = 225; PBO + MTX, n = 395) were included. Patients receiving TCZ + MTX had significantly greater improvement in pain scores and HAQ-DI compared with PBO + MTX in the responder group (–27.19 vs –16.77 and –0.55 vs –0.34, respectively;P< 0.0001 for both) and nonresponder group (–9.59 vs 2.53 and –0.20 vs 0.01;P< 0.0001 for both) at Week 24 (Figure 1). Similar results were seen at Week 16 in the nonresponder group (–11.06 vs –2.38 and –0.23 vs –0.04;P< 0.0001 for both) prior to initiation of rescue treatment. At Week 24 in the responder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS and MCS (9.16 vs 5.71 and 6.55 vs 3.79, respectively;P< 0.0001 for both) (Figure 2) and FACIT-Fatigue (8.39 vs 5.11;P< 0.0001). In the nonresponder group, patients receiving TCZ + MTX had significantly greater improvements compared with PBO + MTX in SF-36 PCS at Week 16 (3.81 vs 1.65;P= 0.0006) and Week 24 (4.42 vs 1.01;P< 0.0001) (Figure 2) and FACIT-Fatigue at Week 16 (3.82 vs 1.32;P= 0.0039) and Week 24 (3.90 vs 1.40;P= 0.0111).Conclusion:Patients with RA who received TCZ + MTX had significantly greater improvements in pain score and other PROs than those who received PBO + MTX regardless of whether they achieved ≥ 20% improvement in SJC. Clinical outcome at Week 24 correlated well with PROs, with a relatively larger improvement in pain score and other PROs in the responder group than in the nonresponder group; relative to PBO + MTX, these improvements appear numerically similar in the responder and nonresponder groups with consistently smaller difference between the groups in TCZ-treated arms. The consistent effect of TCZ on PROs in both responder and nonresponder groups warrants further study on the impact of TCZ on sources of pain independent of that caused by joint inflammation.Figure:Acknowledgments:This study was sponsored by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc, was provided by Genentech, Inc.Disclosure of Interests:Anthony Sebba Consultant of: Genentech, Gilead, Lilly, Regeneron Pharmaceuticals Inc., Sanofi, Speakers bureau: Lilly, Roche, Sanofi, Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.

scholarly journals Full-field stimulus testing: Role in the clinic and as an outcome measure in clinical trials of severe childhood retinal disease

2021 ◽  
pp. 101000
Author(s):  
Alejandro J. Roman ◽  
Artur V. Cideciyan ◽  
Vivian Wu ◽  
Alexandra V. Garafalo ◽  
Samuel G. Jacobson
Keyword(s):  
Clinical Trials ◽  
Outcome Measure ◽  
Retinal Disease ◽  
Full Field

scholarly journals Caries Removal by Chemomechanical (Carisolv™) vs. Rotary Drill: A Systematic Review

2015 ◽  
Vol 9 (1) ◽  
pp. 462-472 ◽  
Author(s):  
Viral P. Maru ◽  
B.S. Shakuntala ◽  
C. Nagarathna
Keyword(s):  
Clinical Trials ◽  
Patient Preference ◽  
Pain Perception ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Random Effect ◽  
Search Results ◽  
Randomized Controlled Studies ◽  
Caries Removal ◽  
Time Required

Background:Chemomechanical caries removal is an effective alternative to the traditional rotary drilling method. The advantages of chemomechanical techniques in terms of the need for anesthesia, pain perception and patient preference are systematically reviewed and a meta-analysis of the time required for caries removal is reported.Method: Randomized controlled studies of comparison of chemomechanical techniques with conventional rotary drill were selected from a systematic search of standard biomedical databases, including the PubMed and Cochrane clinical trials. Non-repeated search results were screened for relevance and risk of bias assessment, followed by methodology assessment. Statistical models were applied to the outcome parameters - time required, pain perception, need of anesthesia and patient preference - extracted from the studies.Results: Out of the 111 non-repeated search results, 26 studies receiving a low bias score were selected for the review, and 16 randomized clinical trials of rotary and Carisolv techniques were considered for meta-analysis. Meta-analysis by fixed effect as well as random effect models indicate that Carisolv takes more time (3.65 ± 0.05 and 4.09 ± 0.29 min) than rotary drill (8.65 ± 0.09 and 8.97 ± 0.66 min) method. Advantages of reduced pain (14.67 for Carisolvvs.6.76 for rotary drill), need for anesthesia (1.59%vs.10.52%) outweigh the longer time requirement and make it the preferred (18.68%vs.4.69%) method.Conclusion: Chemomechanical techniques stand out as a minimally invasive and preferred method based on the meta-analyses. Evaluation of pain experienced using robust methods is needed to strengthen the evidence for their use.

scholarly journals 543 Sensitive quantification and tracking of the active components of a Clonal Neoantigen T cell (cNeT) therapy: From manufacture to peripheral circulation

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A572-A572
Author(s):  
Samra Turajlic ◽  
Mariam Jamal-Hanjani ◽  
Andrew Furness ◽  
Ruth Plummer ◽  
Judith Cave ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Active Sites ◽  
Active Component ◽  
Ex Vivo ◽  
Immune Monitoring ◽  
Patient Specific ◽  
Active Components ◽  
Link Type ◽  
The Uk

BackgroundEx-vivo expanded tumour infiltrating lymphocytes (TIL) show promise in delivering durable responses among several solid tumour indications. However, characterising, quantifying and tracking the active component of TIL therapy remains challenging as the expansion process does not distinguish between tumour reactive and bystander T-cells. Achilles Therapeutics has developed ATL001, a patient-specific TIL-based product, manufactured using the VELOS™ process that specifically targets clonal neoantigens present in all tumour cells within a patient. Two Phase I/IIa clinical trials of ATL001 are ongoing in patients with advanced Non-Small Cell Lung Cancer, CHIRON (NCT04032847), and metastatic or recurrent melanoma, THETIS (NCT03997474). Extensive product characterisation and immune-monitoring are performed through Achilles’ manufacturing and translational science programme. This enables precise quantification and characterisation of the active component of this therapy – Clonal Neoantigen T cells (cNeT) – during manufacture and following patient administration, offering unique insight into the mechanism of action of ATL001 and aiding the development of next generation processes.MethodsATL001 was manufactured using procured tumour and matched whole blood from 8 patients enrolled in the THETIS (n=5) and CHIRON (n=3) clinical trials. Following administration of ATL001, peripheral blood samples were collected up to week 6. The active component of the product was detected via re-stimulation with clonal neoantigen peptide pools and evaluation of IFN-γ and/or TNF-α production. Deconvolution of individual reactivities was achieved via ELISPOT assays. Immune reconstitution was evaluated by flow cytometry. cNeT expansion was evaluated by restimulation of isolated PBMCs with peptide pools and individual peptide reactivities (ELISPOT).ResultsThe median age was 57 (range 30 – 71) and 6/8 patients were male. The median number of previous lines of systemic anti-cancer treatment at the time of ATL001 dosing was 2.5 (range 1 – 5). Proportion of cNeT in manufactured products ranged from 0.20% - 77.43% (mean 26.78%) and unique single peptide reactivities were observed in 7 of 8 products (range 0 – 28, mean 8.6). Post-dosing, cNeTs were detected in 5/8 patients and cNeT expansion was observed in 3/5 patients.ConclusionsThese data underscore our ability to sensitively detect, quantify and track the patient-specific cNeT component of ATL001 – during manufacture and post dosing. As the dataset matures, these metrics of detection and expansion will be correlated with product, clinical and genomic characteristics to determine variables associated with peripheral cNeT dynamics and clinical response.ReferencesNCT04032847, NCT03997474Ethics ApprovalThe first 8 patients described have all been located within the UK and both trials (CHIRON and THETIS) have been approved by the UK MHRA (among other international bodies, e.g FDA). Additionally, these trials have been approved by local ethics boards at active sites within the UK. Patient‘s are fully informed by provided materials and investigators prior to consenting to enrol into either ATL001 trial.

scholarly journals An empirical study of affective and cognitive functions in Compulsive Sexual Behavior Disorder

2021 ◽  
Author(s):  
Małgorzata Draps ◽  
Guillaume Sescousse ◽  
Mateusz Wilk ◽  
Katarzyna Obarska ◽  
Izabela Szumska ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Significant Interaction ◽  
Behavior Disorder ◽  
Stop Signal Task ◽  
Group Differences ◽  
Compulsive Sexual Behavior ◽  
Delay Task ◽  
Sensorimotor Systems ◽  
Punishment Sensitivity ◽  
Positive Valence

AbstractBackground and aimsDespite the inclusion of the Compulsive Sexual Behavior Disorder (CSBD) in the International Classification of Diseases, very little is known about the underlying affective and cognitive processes. To fill this gap, we compared CSBD subjects and Healthy-Controls (HC) across negative/positive valence, cognitive and sensorimotor systems, as proposed by the Research Domain Criteria framework.Methods74 heterosexual CSBD and 66 matched HC males were studied with 10 questionnaires and 8 behavioral tasks. Analyses were conducted with frequent and Bayesian statistics.ResultsCSBD individuals showed significantly higher (than HC) punishment sensitivity, anxiety, depression, compulsivity, and impulsivity symptoms. Frequentist statistical analysis revealed significant interaction between subject group and condition in Incentive Delay Task, concerning the strength of motivation and hedonic value of erotic rewards. Bayesian analysis produced evidence for the absence of group differences in Facial Discrimination Task, Risk-Ambiguity Task, and Learning Task. Also, Bayesian methods provided evidence for group differences in the Emotional Stroop Task and the Incentive Delay Task. Sexual Discounting Task, Attentional Network Task, and Stop Signal Task produced mixed results.ConclusionsHigher punishment sensitivity and impulsivity among CSBD subjects, along with significant interaction between these groups and erotic vs. non-erotic reward processing is in line with previous findings on negative/positive valence alterations in CSBD patients. This result shows that there are similarities to substance and behavioral addictions. The absence of group differences and mixed results related to cognitive and sensorimotor systems raise concerns to what extent CSBD resembles a wide spectrum of impairments observed in disorders, and demand further research.

scholarly journals Movement-Evoked Pain Versus Pain at Rest in Postsurgical Clinical Trials and Meta-Analyses: Protocol for a Follow-Up Systematic Review

10.2196/15309 ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. e15309
Author(s):  
Daenis Camiré ◽  
Jason Erb ◽  
Henrik Kehlet ◽  
Timothy Brennan ◽  
Ian Gilron
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Postoperative Pain ◽  
Primary Outcome ◽  
Outcome Measure ◽  
Pain Treatment ◽  
Pain Outcome ◽  
Meta Analyses ◽  
Pain At Rest

Background Postoperative pain is one of the most prevalent and disabling complications of surgery that is associated with personal suffering, delayed functional recovery, prolonged hospital stay, perioperative complications, and chronic postsurgical pain. Accumulating evidence has pointed to the important distinction between pain at rest (PAR) and movement-evoked pain (MEP) after surgery. In most studies including both measures, MEP has been shown to be substantially more severe than PAR. Furthermore, as MEP is commonly experienced during normal activities (eg, breathing, coughing, and walking), it has a greater adverse functional impact than PAR. In a previous systematic review conducted in 2011, only 39% of reviewed trials included MEP as a trial outcome and 52% failed to identify the pain outcome as either PAR or MEP. Given the recent observations of postsurgical pain trials that continue to neglect the distinction between PAR and MEP, this updated review seeks to evaluate the degree of progress in this area. Objective This updated review will include postsurgical clinical trials and meta-analyses in which the primary outcome was early postoperative pain intensity. The primary outcome for this review is the reporting of MEP (vs PAR) as an outcome measure for each trial and meta-analysis. Secondary outcomes include whether trials and meta-analyses distinguished between PAR and MEP. Methods To be consistent with the 2011 review that we are updating, this review will again focus on randomized controlled trials and meta-analyses, from Medical Literature Analysis and Retrieval System Online and EMBASE databases, focusing on pain treatment after thoracotomy, knee arthroplasty, and hysterectomy in humans. Trials and meta-analyses will be characterized as to whether or not they assessed PAR and MEP; whether their pain outcome acknowledged the distinction between PAR and MEP; and, for trials assessing MEP, which pain-evoking maneuver(s) were used. Results Scoping review and pilot data extraction are under way, and the results are expected by March 2020. Conclusions It is our belief that every postsurgical analgesic trial should include MEP as an outcome measure. The previous 2011 review was expected to have an impact on more widespread assessment of MEP in subsequent postoperative pain treatment trials. Thus, the purpose of this follow-up review is to reevaluate the frequency of use of MEP as a trial outcome, compared with PAR, in more recently published postoperative pain trials. Trial Registration PROSPERO CRD42019125855; https://tinyurl.com/qw9dty8 International Registered Report Identifier (IRRID) DERR1-10.2196/15309

scholarly journals Capillaroscopy as an Outcome Measure for Clinical Trials on the Peripheral Vasculopathy in SSc—Is It Useful?

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Maurizio Cutolo ◽  
Alberto Sulli ◽  
Carmen Pizzorni ◽  
Vanessa Smith
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Outcome Measure ◽  
Digital Ulcers ◽  
Nailfold Videocapillaroscopy ◽  
Therapeutic Trials ◽  
Specific Serum ◽  
Pulmonary Arterial ◽  
Microvascular Impairment ◽  
Clinical Conditions

Peripheral microvascular impairment in systemic sclerosis (SSc) may be easily detected and scored in a safe noninvasive way by nailfold videocapillaroscopy (NVC). The paper highlights clinical conditions related to SSc in which NVC may represent an outcome measure of therapeutical interventions, by elaborating on their already assessed relationship with the NVC patterns and eventually scores. The 3 important biological/clinical conditions are: the positivity for SSc-specific serum autoantibodies, the presence of SSc skin digital ulcers (DUs) and of pulmonary arterial hypertension (PAH) SSc associated. In conclusion, to the question if capillaroscopy (NVC) may represent in SSc an outcome measure for clinical trials on the peripheral vasculopathy, based on the growing evidence and our detailed studies, the answer is positive. Recent therapeutic trials in SSc are confirming this role, and the experience is growing rapidly.

Sign in / Sign up

Export Citation Format

Share Document