Clinical Trial Preparedness Research Articles

Facioscapulohumeral Muscular Dystrophy

This article reviews the current knowledge on the clinical characteristics and disease mechanism of facioscapulohumeral muscular dystrophy (FSHD), as well as advances in targeted therapy development. FSHD has a wide range of severity, yet a distinct phenotype characterized by weakness of the facial, shoulder, and upper arm muscles, followed by weakness of the trunk and leg muscles. It can be caused by two genetic mechanisms that share a common downstream pathway, namely, the epigenetic derepression and subsequent misexpression of the myotoxic DUX4 transcription factor. Treatment is currently supportive and outlined in evidence-based guidelines. Advances in the understanding of the pathogenic mechanism of FSHD are paving the way for targeted therapy development. Approaches for targeted therapies to reduce DUX4 expression that are currently being explored include small molecules, antisense oligonucleotides, vector-based RNA interference, and gene therapy. In anticipation of more clinical trials, "clinical trial preparedness," including the development of sensitive biomarkers and clinical outcome measures, are needed. The cornerstones of the diagnosis of FSHD are clinical observation and genetic testing. Management is currently supportive, but progress in the understanding of the disease mechanism has shifted the field of FSHD toward targeted therapy development.

P.497 - Axial myopathy in patients with neuromuscular diseases

Muscle atrophy and weakness of upper and lower extremity muscles are well characterized in neuromuscular diseases, but involvement of the axial muscles is poorly understood. Since the axial musculature stabilizes and moves the trunk and provides stability for movement of the extremities, knowledge about the axial musculature in patients with neuromuscular diseases is important. Studies have shown that the axial muscles are affected in a number of myopathies, such as RYR1-myopathy and facioscapulohumeral muscular dystrophy. However, axial myopathy has not been investigated in patients with limb-girdle and Becker muscular dystrophy, and Charcot-Marie-Tooth disease. The purpose of the study is; (1) to investigate the involvement of axial muscles in patients with neuromuscular diseases, (2) to evaluate psychometric properties of stationary dynamometry in patients with axial myopathy, and (3) to investigate the relationship between axial weakness and rigidity, posture, balance and pain. The design is an exploratory cross-sectional study. Fifty adult patients with limb-girdle and Becker muscular dystrophies and Charcot-Marie-Tooth disease and 50 healthy controls, matched for age, sex and body mass index, will be recruited. Patients will be examined in relation to range of motion, manual muscle test, hand-held dynamometry, isometric stationary dynamometry (Biodex System 4 Pro), magnetic resonance imaging, photographic posture analysis, Clinical Test of Sensory Integration and Balance (Biosway), Trunk Control Test, Fatigue Severity Scale, Low Back Pain Rating scale, and The Danish SF-36 Health Survey. This study will increase the understanding of axial muscle involvement in patients with neuromuscular diseases and contribute to diagnostic specificity. The evidence-basing of stationary dynamometry to measure trunk muscle strength in patients with axial myopathy is needed for clinical practice and clinical trial preparedness. Preliminary results will be presented at the poster.

Engaging adolescents in tuberculosis and clinical trial research through drama.

BackgroundThe South African Tuberculosis Vaccine Initiative is based in Worcester where tuberculosis (TB) is endemic, and incidence rates are amongst the highest nationally. In high TB burden settings after an early childhood peak, incidence rates start to rise again in adolescents, therefore they are an important target group for tuberculosis vaccine research. In 2012, learners from a local school developed a one-off theatrical production out of an educational comic book Carina’s Choice, developed by the South African Tuberculosis Vaccine Initiative in 2010. A Wellcome Trust International Engagement grant allowed for this one-off production to be further developed, with input from university students and staff, and rolled out to schools in the Worcester area as an engagement and education intervention.MethodsFocus group feedback was used to identify key messages and to develop the play’s script. Qualitative methods were used to collect and analyse relevant data. Interviews were conducted with learner-actors, pre- and post-focus group feedback was obtained from a sample of school-going adolescents, and pre- and post-questionnaires were administered to adolescent audience members.ResultsFrom the pre-drama focus group discussions, topics such as TB symptoms, stigma and transmission were identified as areas that needed attention. After the performances, adolescents showed improved knowledge on the identified topics and they discussed TB prevention measures. They highlighted transmission of TB during pregnancy as a further topic to be addressed in future iterations of the drama. Although stigma is a difficult phenomenon to interpret, post-drama participants understood that TB transmission could occur in all individuals. Learner-actors agreed with focus group participants that the play could impact the wider community if it were rolled out. Feedback from the South African Tuberculosis Vaccine Initiative staff verified that recruitment for an upcoming trial was facilitated by the preparedness that the play provided in recruitment areas. The study showed that before and after evaluations provide data on the usefulness of the play as an education tool.ConclusionsTheatre, presented and motivated by adolescent peers, can raise awareness of TB, and assist clinical trial preparedness and further engagement between trial staff and their trial community.

Clinical trial preparedness in facioscapulohumeral muscular dystrophy: Clinical, tissue, and imaging outcome measures 29–30 May 2015, Rochester, New York

Clinical trial preparedness in facioscapulohumeral muscular dystrophy: Clinical, tissue, and imaging outcome measures 29–30 May 2015, Rochester, New York Rabi Tawil *, George W. Padberg , Dennis W. Shaw , Silvere M. van der Maarel , Stephen J. Tapscott , The FSHD Workshop Participants 1 a Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA b Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands c Department of Radiology, Seattle Children’s Hospital, Seattle, WA, USA d Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands e Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

G.P.329 - Giant axonal neuropathy – clinical trial preparedness and evaluation of markers of disease severity

G.P.329 - Giant axonal neuropathy – clinical trial preparedness and evaluation of markers of disease severity

Pregnancy incidence and correlates in a clinical trial preparedness study, North West Province South Africa.

IntroductionWomen in HIV prevention trials often must typically agree to avoid pregnancy. Regardless, some become pregnant. Screening tools predicting pregnancy risk could maximize trial safety and efficiency.ObjectivesWe assessed incidence and correlates of pregnancy among women at high HIV risk.MethodsWe enrolled sexually-active, HIV-negative women into an observational cohort (2008–2011). At enrolment demographic, contraceptive, reproductive, pregnancy intention and behavioural data were collected. Women reported if one or both partners wanted or intended for the couple to become pregnant. We measured gender role beliefs using a locally validated eight-point index. We tested HIV and pregnancy, and inquired about sexually transmitted infection symptoms (STIs) at enrollment and monthly. HIV testing included behavioural counselling and condom provision, but did not specifically counsel women to avoid pregnancy. Cox proportional hazard modelling evaluated the associations with pregnancy. The multivariate model included the following variables “Recent pregnancy attempts”, “Gender Roles Beliefs”, ”Self-reported STIs” and “Age”.ResultsWe screened 1068 women and excluded (24.6%, 263/1068) who did not report risk behaviour. Non-pregnant, non-sterilized women aged 18–35 (median = 21 years) enrolled (n = 438). Most women reported one partner (74.7%) and a prior live birth (84.6%). Median follow-up time was 6 months (range 0.7–15.5). Pregnancy incidence was 25.1 per 100 women-years (n = 57 pregnancies). Conservative beliefs on gender roles (Adjusted Hazard Ratio (aHR) 1.8; 95% confidence interval [CI] 1.1–2.9), recent pregnancy attempts (aHR 1.9; 95% CI 1.1–3.4) and baseline self-reported STI (aHR 2.5; 95% CI 1.4–4.4) were associated with increased incident pregnancy. Report of no pregnancy intention was associated with lowered pregnancy risk (aHR 0.3; 95% CI 0.1–0.7).ConclusionsWe identified new and confirmed existing factors that can facilitate screening for pregnancy risk.

Knowledge, Attitudes, and Self-efficacy as Predictors of Preparedness for Oncology Clinical Trials

This study used the Ottawa Decision Support Framework to evaluate a model examining associations between clinical trial knowledge, attitudinal barriers to participating in clinical trials, clinical trial self-efficacy, and clinical trial preparedness among 1256 cancer patients seen for their first outpatient consultation at a cancer center. As an exploratory aim, moderator effects for gender, race/ethnicity, education, and metastatic status on associations in the model were evaluated. . Patients completed measures of cancer clinical trial knowledge, attitudinal barriers, self-efficacy, and preparedness. Structural equation modeling (SEM) was conducted to evaluate whether self-efficacy mediated the association between knowledge and barriers with preparedness. . The SEM explained 26% of the variance in cancer clinical trial preparedness. Self-efficacy mediated the associations between attitudinal barriers and preparedness, but self-efficacy did not mediate the knowledge-preparedness relationship. . Findings partially support the Ottawa Decision Support Framework and suggest that assessing patients' level of self-efficacy may be just as important as evaluating their knowledge and attitudes about cancer clinical trials.

Clinical trial preparedness in facioscapulohumeral dystrophy: Outcome measures and patient access: 8–9 April 2013, Leiden, The Netherlands

Thirty participants from eight countries representing academic centers and advocacy groups met on 8–9 April, 2013 for a workshop on clinical trial preparedness in facioscapulohumeral muscular dystrophy (FSHD). The aims of the workshop were to discuss ways to facilitate patient access to clinical trials and to reach consensus on the development of the most appropriate clinical and surrogate outcome measures for future clinical trials. FSHD is one of the most common forms of muscular dystrophy with a prevalence of 1:15,000–1:20,000 [1,2]. A dominantly inherited disease, in its most common form, FSHD is slowly progressive and causes significant lifetime morbidity, with up to 20% above age 50 requiring full time wheelchair use. The clinical spectrum of disease severity is wide and the regional distribution of muscle weakness and the pattern of progression are unique. Muscle weakness typically starts in the face and shoulders, often with striking side-to-side asymmetry, with a descending progression to involve first the distal lower extremity muscle before affecting the hip girdle muscles. Non muscular involvement in FSHD includes hearing loss and retinal vascular disease, which are typically symptomatic only in patients with the largest deletions.

P2-S1.06 Adolescents' willingness to participate in HIV vaccine clinical trial preparedness in Nigeria

BackgroundRoutine vaccination of recommended vaccines in adolescents/children from 1999 would prevent >14 million disease cases and 33 000 deaths over the lifetime of each birth cohort. Data from National sero-prevalence...

204 Adolescents' Willingness to Participate in HIV Vaccine Clinical Trial Preparedness in Nigeria

204 Adolescents' Willingness to Participate in HIV Vaccine Clinical Trial Preparedness in Nigeria