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Study Treatment (study + treatment)
Selected AbstractsA Double-Blind Comparison of OnabotulinumtoxinA (BOTOX®) and Topiramate (TOPAMAX®) for the Prophylactic Treatment of Chronic Migraine: A Pilot StudyHEADACHE, Issue 10 2009Ninan T. Mathew MD Background., There is a need for effective prophylactic therapy for chronic migraine (CM) that has minimal side effects. Objective., To compare the efficacy and safety of onabotulinumtoxinA (BOTOX®, Allergan, Inc., Irvine, CA) and topiramate (TOPAMAX®, Ortho-McNeil, Titusville, NJ) prophylactic treatment in patients with CM. Methods., In this single-center, double-blind trial, patients with CM received either onabotulinumtoxinA, maximum 200 units (U) at baseline and month 3 (100 U fixed-site and 100 U follow-the-pain), plus an oral placebo, or topiramate, 4-week titration to 100 mg/day with option for additional 4-week titration to 200 mg/day, plus placebo saline injections. OnabotulinumtoxinA or placebo saline injection was administered at baseline and month 3 only, while topiramate oral treatment or oral placebo was continued through the end of the study. The primary endpoint was treatment responder rate assessed using Physician Global Assessment 9-point scale (+4 = clearance of signs and symptoms and ,4 = very marked worsening [about 100% worse]). Secondary endpoints included the change from baseline in the number of headache (HA)/migraine days per month (HA diary), and HA disability measured using Headache Impact Test (HIT-6), HA diary, Migraine Disability Assessment (MIDAS) questionnaire, and Migraine Impact Questionnaire (MIQ). The overall study duration was approximately 10.5 months, which included a 4-week screening period and a 2-week optional final safety visit. Follow-up visits for assessments occurred at months 1, 3, 6, and 9. Adverse events (AEs) were documented. Results., Of 60 patients randomized to treatment (mean age, 36.8 ± 10.3 years; 90% female), 36 completed the study at the end of the 9 months of active treatment (onabotulinumtoxinA, 19/30 [63.3%]; topiramate, 17/30 [56.7%]). In the topiramate group, 7/29 (24.1%) discontinued study because of treatment-related AEs vs 2/26 (7.7%) in the onabotulinumtoxinA group. Between 68% and 83% of patients for both onabotulinumtoxinA and topiramate groups reported at least a slight (25%) improvement in migraine; response to treatment was assessed using Physician Global Assessment at months 1, 3, 6, and 9. Most patients in both groups reported moderate to marked improvements at all time points. No significant between-group differences were observed, except for marked improvement at month 9 (onabotulinumtoxinA, 27.3% vs topiramate, 60.9%, P = .0234, chi-square). In both groups, HA/migraine days decreased and MIDAS and HIT-6 scores improved. Patient-reported quality of life measures assessed using MIQ after treatment with onabotulinumtoxinA paralleled those seen after treatment with topiramate in most respects. At month 9, 40.9% and 42.9% of patients in the onabotulinumtoxinA and topiramate groups, respectively, reported ,50% reduction in HA/migraine days. Forty-one treatment-related AEs were reported in 18 onabotulinumtoxinA-treated patients vs 87 in 25 topiramate-treated patients, and 2.7% of patients in the onabotulinumtoxinA group and 24.1% of patients in the topiramate group reported AEs that required permanent discontinuation of study treatment. Conclusions., OnabotulinumtoxinA and topiramate demonstrated similar efficacy in the prophylactic treatment of CM. Patients receiving onabotulinumtoxinA had fewer AEs and discontinuations. [source] Comparison between effects of open grazing and manual harvesting of cultivated summer rangelands of northern Iran on infiltration, runoff and sediment yield,LAND DEGRADATION AND DEVELOPMENT, Issue 6 2007S. H. R. Sadeghi Abstract The effects of grazing and cultivation management on infiltration, runoff and sediment yield on storm basis were quantified for summer rangeland in the Matash mountains (Talesh Region), northern Iran. The infiltration experiments were made using double cylinder infiltrometer with five replicates within each study treatment. The runoff generation and sediment yield were measured using standard plots (1·83,m,×,22·18,m) in three replications. The peak and the terminal instantaneous infiltration, and runoff and sediment rates were compared using independent and paired sample t -test in two aforesaid treatments, respectively. The terminal and the peak instantaneous infiltration rates of 39·6 and 342·9,mm/h showed a respective significant increase (p,<,0·001) of 32 and 39 per cent in cultivated areas compared to those in open grazing treatments. The results of runoff analysis also showed that there was a significant difference (p,<,0·001) in runoff generation in two above-mentioned areas. The runoff water was also found to be 5·63-folds more in case of open grazing treatment in comparison with that generated by cultivated plots. A significant difference (p,<,0·001) in sediment yield between two study treatments was also proved by the results obtained through sediment yield study. The soil loss in open grazing treatment was found to be 26·6 times more than of that occurred in cultivated plots. Copyright © 2007 John Wiley & Sons, Ltd. [source] Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: Results of a randomized, double-blind, placebo-controlled, phase I/II study,ARTHRITIS & RHEUMATISM, Issue 8 2010Mikkel Østergaard Objective To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ,1 disease-modifying antirheumatic drug. Methods This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated. Results AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24. Conclusion Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA. [source] Neutralization of interferon-,/,,inducible genes and downstream effect in a phase I trial of an anti,interferon-, monoclonal antibody in systemic lupus erythematosus,ARTHRITIS & RHEUMATISM, Issue 6 2009Yihong Yao Objective Type I interferons (IFNs) play an important role in the pathogenesis of systemic lupus erythematosus (SLE). This phase Ia trial was undertaken to evaluate the safety, pharmacokinetics, and immunogenicity of anti-IFN, monoclonal antibody (mAb) therapy in SLE. During the trial, we also examined whether overexpression of an IFN,/,-inducible gene signature in whole blood could serve as a pharmacodynamic biomarker to evaluate IFN, neutralization and investigated downstream effects of neutralizing IFN, on BAFF and other key signaling pathways, i.e., granulocyte,macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), tumor necrosis factor , (TNF,), and IL-1,, in SLE. Methods Affymetrix Human Genome U133 Plus 2.0 microarrays were used to profile whole blood and lesional skin of patients receiving standard therapy for mild to moderate SLE. Selected IFN,/,-inducible proteins were analyzed by immunohistochemistry. Results With the study treatment, we observed anti-IFN, mAb,specific and dose-dependent inhibition of overexpression of IFN,/,-inducible genes in whole blood and skin lesions from SLE patients, at both the transcript and the protein levels. In SLE patients with overexpression of messenger RNA for BAFF, TNF,, IL-10, IL-1,, GM-CSF, and their respective inducible gene signatures in whole blood and/or skin lesions, we observed a general trend toward suppression of the expression of these genes and/or gene signatures upon treatment with anti-IFN, mAb. Conclusion IFN,/,-inducible gene signatures in whole blood are effective pharmacodynamic biomarkers to evaluate anti-IFN, mAb therapy in SLE. Anti-IFN, mAb can neutralize overexpression of IFN,/,-inducible genes in whole blood and lesional skin from SLE patients and has profound effects on signaling pathways that may be downstream of IFN, in SLE. [source] Acupuncture in patients with osteoarthritis of the knee or hip: A randomized, controlled trial with an additional nonrandomized armARTHRITIS & RHEUMATISM, Issue 11 2006Claudia M. Witt Objective To investigate the effectiveness of acupuncture in addition to routine care, compared with routine care alone, in the treatment of patients with chronic pain due to osteoarthritis (OA) of the knee or hip. Methods In a randomized, controlled trial, patients with chronic pain due to OA of the knee or hip were randomly allocated to undergo up to 15 sessions of acupuncture in a 3-month period or to a control group receiving no acupuncture. Another group of patients who did not consent to randomization underwent acupuncture treatment. All patients were allowed to receive usual medical care in addition to the study treatment. Clinical OA severity (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) and health-related quality of life (Short Form 36) were assessed at baseline and after 3 months and 6 months. Results Of 3,633 patients (mean ± SD age 61.8 ± 10.8 years; 61% female), 357 were randomized to the acupuncture group and 355 to the control group, and 2,921 were included in the nonrandomized acupuncture group. At 3 months, the WOMAC had improved by a mean ± SEM of 17.6 ± 1.0 in the acupuncture group and 0.9 ± 1.0 in the control group (3-month scores 30.5 ± 1.0 and 47.3 ± 1.0, respectively [difference in improvement 16.7 ± 1.4; P < 0.001]). Similarly, quality of life improvements were more pronounced in the acupuncture group versus the control group (P < 0.001). Treatment success was maintained through 6 months. The changes in outcome in nonrandomized patients were comparable with those in randomized patients who received acupuncture. Conclusion These results indicate that acupuncture plus routine care is associated with marked clinical improvement in patients with chronic OA,associated pain of the knee or hip. [source] Phase II study of irinotecan in combination with capecitabine as a first-line chemotherapy in Asian patients with inoperable hepatocellular carcinomaASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2009Tony MOK Abstract Aim: Hepatocellular carcinoma (HCC) is one of the most commonly fatal malignancies in Asia but treatment options are limited. Methods: This multinational, nonrandomized phase II trial using the combination of irinotecan (Campto or CPT-11) and capecitabine (Xeloda) was conducted to determine efficacy and safety of this combination in Asian patients with advanced inoperable HCC. The starting dose was irinotecan 200 mg/m2 every 3 weeks followed by capecitabine 1000 mg/m2 orally twice daily for 14 days followed by a 7-day rest. The primary endpoint was tumor response rate, based on response evaluation criteria in solid tumors criteria. Secondary objectives included the safety and tolerability of the treatment combination, time to progression, duration of overall response, tumor growth control rate (complete response, partial response plus stable disease) and overall survival. Results: Of the 63 recruited patients, 47 were evaluable. Of these, three (6.4%) achieved a partial response (lasting 2.2, 3.4 and 8.0 months, respectively). The median overall survival was 4.5 months. Grade 4 diarrhea was reported in four patients. Hematologic grade 4 laboratory abnormalities observed in patients while on study treatment included neutropenia (5.2%) and anemia (1.7%). Seven patients (12.1%) had grade 4 elevations in their total bilirubin. Both irinotecan and capecitabine were generally well tolerated, with manageable and reversible toxicities. Conclusion: Combination therapy with irinotecan and capecitabine has limited efficacy in the treatment of advanced-stage HCC. Further investigation of this combination is not warranted. [source] Cox Regression Methods for Two-Stage Randomization DesignsBIOMETRICS, Issue 2 2007Yuliya Lokhnygina Summary Two-stage randomization designs (TSRD) are becoming increasingly common in oncology and AIDS clinical trials as they make more efficient use of study participants to examine therapeutic regimens. In these designs patients are initially randomized to an induction treatment, followed by randomization to a maintenance treatment conditional on their induction response and consent to further study treatment. Broader acceptance of TSRDs in drug development may hinge on the ability to make appropriate intent-to-treat type inference within this design framework as to whether an experimental induction regimen is better than a standard induction regimen when maintenance treatment is fixed. Recently Lunceford, Davidian, and Tsiatis (2002, Biometrics58, 48,57) introduced an inverse probability weighting based analytical framework for estimating survival distributions and mean restricted survival times, as well as for comparing treatment policies at landmarks in the TSRD setting. In practice Cox regression is widely used and in this article we extend the analytical framework of Lunceford et al. (2002) to derive a consistent estimator for the log hazard in the Cox model and a robust score test to compare treatment policies. Large sample properties of these methods are derived, illustrated via a simulation study, and applied to a TSRD clinical trial. [source] Comparison between effects of open grazing and manual harvesting of cultivated summer rangelands of northern Iran on infiltration, runoff and sediment yield,LAND DEGRADATION AND DEVELOPMENT, Issue 6 2007S. H. R. Sadeghi Abstract The effects of grazing and cultivation management on infiltration, runoff and sediment yield on storm basis were quantified for summer rangeland in the Matash mountains (Talesh Region), northern Iran. The infiltration experiments were made using double cylinder infiltrometer with five replicates within each study treatment. The runoff generation and sediment yield were measured using standard plots (1·83,m,×,22·18,m) in three replications. The peak and the terminal instantaneous infiltration, and runoff and sediment rates were compared using independent and paired sample t -test in two aforesaid treatments, respectively. The terminal and the peak instantaneous infiltration rates of 39·6 and 342·9,mm/h showed a respective significant increase (p,<,0·001) of 32 and 39 per cent in cultivated areas compared to those in open grazing treatments. The results of runoff analysis also showed that there was a significant difference (p,<,0·001) in runoff generation in two above-mentioned areas. The runoff water was also found to be 5·63-folds more in case of open grazing treatment in comparison with that generated by cultivated plots. A significant difference (p,<,0·001) in sediment yield between two study treatments was also proved by the results obtained through sediment yield study. The soil loss in open grazing treatment was found to be 26·6 times more than of that occurred in cultivated plots. Copyright © 2007 John Wiley & Sons, Ltd. [source] Rosette Recruitment of a Rare Endemic Forb (Gaura neomexicana Subsp. coloradensis) with Canopy Removal of Associated SpeciesRESTORATION ECOLOGY, Issue 1 2002Linda M. Munk Abstract Gaura neomexicana subsp. coloradensis Munz (Onagraceae), (Colorado butterfly plant), a short-lived perennial forb, became listed as a threatened species by the U.S. Fish and Wildlife Service in October 2000 because of its small global range and population size. This endemic subspecies consists of only 18 extant populations within southeastern Wyoming, southwestern Nebraska, and northeastern Colorado. Wyoming occurrences are on private land with the exception of three occurrences on F. E. Warren Air Force Base, near Cheyenne. Gaura neomexicana subsp. coloradensis may be displaced by many competitors, including Cirsium arvense (L.) Scop. (Canada thistle), an invasive, noxious weed. In June 1998, three G. neomexicana subsp. coloradensis populations were examined for rosette establishment in the presence of and after removal of associated species. The four study treatments removed: (1) Cirsium arvense, (2) grass and forb canopy and associated litter, (3) grass and forb canopy, litter, and C. arvense, and (4) no removal of associated plant species (control). Mature G. neomexicana subsp. coloradensis plants were evaluated for height, number of leaves, and capsule production. The mature plant characteristics monitored in 1998 were not good indicators of subsequent G. neomexicana subsp. coloradensis rosette densities in the following spring. Recruitment was assessed by counting new rosettes in the fall 1999. Although both G. neomexicana subsp. coloradensis and the exotic C. arvense have comparable habitat, removal of C. arvense did not increase G. neomexicana subsp. coloradensis vegetative growth, seed capsule production, or rosette density. Removal of other forbs, grass, and litter, however, increased G. neomexicana subsp. coloradensis rosette density in the following two years, indicating that canopy removal of associated species can enhance rosette establishment of this rare native. The accumulation of dense vegetative cover and litter associated with the absence of herbivory and fire may contribute to the decline of rare species in rich riparian habitats. Return of herbivory and fire in mesic sites to reduce standing biomass accumulations should be considered in restoring recruitment potential to rare monocarpic species. [source] Effects of experimenting with physical and virtual manipulatives on students' conceptual understanding in heat and temperatureJOURNAL OF RESEARCH IN SCIENCE TEACHING, Issue 9 2008Zacharias C. Zacharia Abstract This study aimed to investigate the comparative value of experimenting with physical manipulatives (PM) in a sequential combination with virtual manipulatives (VM), with the use of PM preceding the use of VM, and of experimenting with PM alone, with respect to changes in students' conceptual understanding in the domain of heat and temperature. A pre,post-comparison study design was used which involved 62 undergraduate students that attended an introductory course in physics. The participants were randomly assigned to one experimental and one control group. Both groups used the same inquiry-oriented curriculum materials. Participants in the control group used PM to conduct the experiments, whereas, participants in the experimental group used first PM and then VM. VM differed from PM in that it could provide the possibility of faster manipulation, whereas, it retained any other features and interactions of the study's subject domain identical to the PM condition. Conceptual tests were administered to assess students' understanding before, during, and after the study's treatments. Results indicated that experimenting with the combination of PM and VM enhanced students' conceptual understanding more than experimenting with PM alone. The use of VM was identified as the cause of this differentiation. © 2008 Wiley Periodicals, Inc. J Res Sci Teach 45: 1021,1035, 2008 [source] | ||||||||||