scholarly journals Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242945
Author(s):  
Graham Devereux ◽  
Danielle Wrolstad ◽  
Stephen J. Bourke ◽  
Cori L. Daines ◽  
Simon Doe ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cystic Fibrosis ◽  
Randomized Clinical Trial ◽  
Outcome Measures ◽  
Leukocyte Count ◽  
Bacterial Load ◽  
Adjunct Treatment ◽  
Dosing Regimens ◽  
Pulmonary Exacerbations ◽  
Blood Leukocyte

Background Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? Methods and findings Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire–Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. Conclusion In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. Clinical trial registration NCT03000348; www.clinicaltrials.gov.

scholarly journals Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Sílvia M. Illamola ◽  
Hoa Q. Huynh ◽  
Xiaoxi Liu ◽  
Zubin N. Bhakta ◽  
Catherine M. Sherwin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Population Pharmacokinetics ◽  
Drug Disposition ◽  
Adult Patients ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Concentration Data ◽  
First Order ◽  
Dosing Regimens ◽  
Pulmonary Exacerbations

ABSTRACTPractitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect the amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient characteristics for adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling with the first-order conditional estimation method. A two-compartment model with first-order elimination best described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for clearance and the volume of distribution, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volumes of distribution, and intercompartmental clearance were 3.06 liters/h, 14.4 liters, 17.1 liters, and 0.925 liters/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ from those in individuals without cystic fibrosis. However, further investigations are needed to confirm these results and, thus, the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish the optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

Incidence of Decreased Hip Range of Motion in Youth Soccer Players and Response to a Stretching Program: A Randomized Clinical Trial

2013 ◽  
Vol 22 (2) ◽  
pp. 100-107 ◽  
Author(s):  
Jacqueline Vieira de Castro ◽  
Karina Costa Machado ◽  
Kelly Scaramussa ◽  
João Luiz Ellera Gomes
Keyword(s):  
Clinical Trial ◽  
Range Of Motion ◽  
Randomized Clinical Trial ◽  
Outcome Measures ◽  
University Hospital ◽  
Soccer Players ◽  
Youth Soccer ◽  
Wide Range ◽  
Hip Rotation ◽  
Stretching Exercises

Context:After years of focusing on the management of anterior cruciate ligament (ACL) injuries, the most common soccer-related injuries, the orthopedic community has concluded that soccer players have a wide range of variation in joint biomechanics and has thus started to focus research efforts on the morphological factors that might contribute to ACL trauma. One such factor is decreased hip-rotation range of motion (ROM), which may be due to compensatory musculoskeletal changes occurring in response to longstanding soccer practice since childhood.Objective:This study sought to assess decreased hip rotation and the influence of stretching exercises on the behavior of the hip joint in players of the youth soccer categories of a Brazilian soccer team.Design:Randomized clinical trial.Setting:University hospital.Patients:262 male soccer players.Interventions:Subjects were randomly allocated into 2 groups—control or a stretching program.Main Outcome Measures:Subjects were reassessed after 12 wk.Results:The findings suggest that hip-rotation ROM decreases over the years in soccer players. In the study sample, adherence to a stretching program improved only external hip-rotation ROM in the nondominant limb.Conclusion:Playing soccer can restrict rotation ROM of the hip, and adherence to stretching exercises may decrease the harmful effects on the hip joints.

Inhalation Treatment with Glutathione in Patients with Cystic Fibrosis. A Randomized Clinical Trial

2013 ◽  
Vol 188 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Matthias Griese ◽  
Matthias Kappler ◽  
Claudia Eismann ◽  
Manfred Ballmann ◽  
Sibylle Junge ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cystic Fibrosis ◽  
Randomized Clinical Trial

Clinical outcomes with the Prestige II cervical disc: preliminary results from a prospective randomized clinical trial

2004 ◽  
Vol 17 (3) ◽  
pp. 1-43 ◽  
Author(s):  
Francois Porchet ◽  
Newton H. Metcalf
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Outcome Measures ◽  
Cervical Disc ◽  
Cervical Disc Disease ◽  
Disc Disease ◽  
Prospective Randomized Clinical Trial ◽  
Treatment Groups ◽  
Preliminary Results ◽  
The Prestige

Object A prospective, randomized clinical trial was conducted to compare the Prestige II Cervical Disc with anterior decompression and fusion for the treatment of single-level degenerative disease. Standardized clinical outcome measures and radiographic examinations were used at prescribed postoperative intervals to compare the treatment groups. Methods Patients with symptomatic single-level cervical disc disease who met the inclusion/exclusion criteria defined in the protocol were randomized to receive the Prestige II disc or iliac crest autograft fusion. All patients underwent a standardized neurological and radiographic examination and completed outcomes questionnaires (Neck Disability Index and Short Form–36) preoperatively and at each postoperative interval (6 weeks and 3, 6, 12, and 24 months). Two independent radiologists reviewed all x-ray films and assessed motion at the treated level and adjacent segments. Standard statistical methods were used to compare all outcome measures. Preliminary results in 55 patients enrolled in the study are presented. Several patients have reached the final (24-month) follow-up interval. Clinical and radiographic results are encouraging, with significant improvement seen in both treatment groups. Radiographic results show that the Prestige II disc maintains motion at the treated level without adjacent-segment compromise. Conclusions Cervical spine arthroplasty is an exciting and rapidly developing surgical treatment option. An objective comparison with fusion is important to advance this option. This is the first prospective randomized trial in which cervical arthroplasty is compared with fusion. The preliminary results from this limited number of patients indicate that the Prestige II disc is potentially a viable alternative to fusion for primary cervical disc disease; however, further clinical studies with larger sample sizes will be required to show statistical equivalence.

scholarly journals Pain-Guided Activity Modification During Treatment for Patellar Tendinopathy: A Feasibility and Pilot Randomized Clinical Trial

2021 ◽  
Author(s):  
Andrew L Sprague ◽  
Christian Couppé ◽  
Ryan T. Pohlig ◽  
Lynn Sc.D Snyder-Mackler ◽  
Karin Grävare Silbernagel
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Outcome Measures ◽  
Quadriceps Muscle ◽  
Recruitment Rate ◽  
Muscle Performance ◽  
Patellar Tendinopathy ◽  
Lower Extremity Function ◽  
Smallest Detectable Change ◽  
The Impact

Abstract Background: Activity modification is a key component of patellar tendinopathy treatment but there is a lack of evidence guiding activity modification prescription. Use of activity modification in treatment studies has varied widely and the impact of those recommendations has not been directly investigated or compared. The purpose of this study was to assess 1) the feasibility of using pain-guided activity modification during treatment for patellar tendinopathy and 2) if our outcome measures are responsive to changes in tendon health over the course of treatment.Methods: This was an unblinded, randomized two-arm pilot and feasibility study randomized clinical trial with parallel assignment, conducted in Newark, DE. Individuals between the ages of 16 and 40 years old with patellar tendinopathy were included. Participants were randomly assigned to a pain-guided activity (PGA) or pain-free activity (PFA) group using a spreadsheet-based randomization scheme. All participants received standardized treatment using a modified version of the heavy-slow resistance protocol 3x/week for 12-weeks. For the first six weeks, the PGA group used the Pain-Monitoring Model to guide activity outside of treatment and the PFA group was restricted from running, jumping, or activities that provoked their patellar tendon pain. Feasibility outcomes included recruitment, enrollment, randomization, compliance, and retention percentages. Clinical evaluations were conducted at baseline, 6- and 12-weeks to assess symptom severity, psychological factors, tendon morphology and mechanical properties, lower extremity function and quadriceps muscle performance. Results: In a ~13-month period, 108 individuals were screened, 47/108 (43.5%) were eligible for participation, and 15/47 (32.0%) of those were enrolled (9 PGA, 6 PFA). The recruitment rate was 1.15 participants/month. The mean±SD compliance with treatment was PGA: 86.1±13.0% and PFA: 67.1±30.7%. There was one missed evaluation session and two adverse events, which were not due to study interventions. Changes exceeding the smallest detectable change were observed for at least one outcome in each domain of tendon health.Conclusions: Use of pain-guided activity modification during exercise therapy for patellar tendinopathy was found to be feasible, and the proposed outcome measures appropriate. Computer-based allocation concealment, blinding of evaluators, and greater recruitment of high-level athletes should be implemented in future trials.

Multicenter Randomized Clinical Trial Evaluating the Effectiveness of the Lokomat in Subacute Stroke

2008 ◽  
Vol 23 (1) ◽  
pp. 5-13 ◽  
Author(s):  
Joseph Hidler ◽  
Diane Nichols ◽  
Marlena Pelliccio ◽  
Kathy Brady ◽  
Donielle D. Campbell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Outcome Measures ◽  
Walking Speed ◽  
Gait Training ◽  
Secondary Outcome ◽  
Walking Ability ◽  
Robotic Assisted ◽  
Subacute Stroke

Objective. To compare the efficacy of robotic-assisted gait training with the Lokomat to conventional gait training in individuals with subacute stroke. Methods. A total of 63 participants <6 months poststroke with an initial walking speed between 0.1 to 0.6 m/s completed the multicenter, randomized clinical trial. All participants received twenty-four 1-hour sessions of either Lokomat or conventional gait training. Outcome measures were evaluated prior to training, after 12 and 24 sessions, and at a 3-month follow-up exam. Self-selected overground walking speed and distance walked in 6 minutes were the primary outcome measures, whereas secondary outcome measures included balance, mobility and function, cadence and symmetry, level of disability, and quality of life measures. Results. Participants who received conventional gait training experienced significantly greater gains in walking speed ( P = .002) and distance ( P = .03) than those trained on the Lokomat. These differences were maintained at the 3-month follow-up evaluation. Secondary measures were not different between the 2 groups, although a 2-fold greater improvement in cadence was observed in the conventional versus Lokomat group. Conclusions. For subacute stroke participants with moderate to severe gait impairments, the diversity of conventional gait training interventions appears to be more effective than robotic-assisted gait training for facilitating returns in walking ability.

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