Task force on alzheimer's disease trial methodology: Recruitment and retention, data management and analysis. the use of imaging in recruitment: Maintenance and methodological issues in Alzheimer's trials
Suhy J.,SYNARC Inc.
Journal of Nutrition, Health and Aging | Year: 2012
Imaging has been used in clinical trials for decades and has proven a useful biomarker in many disease states. Although imaging is not widely used in clinical practice for AD patient care, many pharmaceutical and biotech companies have relied on this technique for eligibility, safety and efficacy roles in their trials. In this overview, issues with standardization, validation and regulations will be discussed in order to gain a better understanding of the benefits, risks and impact on study conduct of adding imaging to Alzheimer's disease clinical trials.
Synarc Inc. | Date: 2010-06-03
A method of manipulation of a representation of a 2-D shape for improving a General Procrustes Alignment process, comprising taking a starting 2-D shape defined by a set of landmarks derived from data representing a 2-D projection image of a body part such as a vertebra, in a suitably programmed computing device deriving for each landmark of the 2-D shape a probable relative depth by the application thereto of a statistical model based on a multiplicity of 3-D shapes defined by landmarks derived from 3-D images of similar said body parts, said landmarks having one depth and two spatial coordinates, said model relating the probable relative depth of each landmark in a 3-D-shape of a said body part to the spatial coordinates of the set of landmarks constituting a said shape, and based on the inferred relative depth of the landmarks of the starting 2-D shape deforming the starting 2-D shape to correct for apparent distortion caused by rotation about an axis parallel to the projection plane of the imaged body part, so producing a corrected 2-D shape.
Fitzpatrick L.A.,Glaxosmithkline |
Dabrowski C.E.,Glaxosmithkline |
Cicconetti G.,Glaxosmithkline |
Gordon D.N.,Glaxosmithkline |
And 5 more authors.
Journal of Bone and Mineral Research | Year: 2012
Intermittent injections of parathyroid hormone have osteoanabolic effects that increase bone mineral density (BMD). Ronacaleret is an orally administered calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release from the parathyroid glands. Our objective was to compare the effects of ronacaleret and teriparatide on volumetric BMD (vBMD) measured by quantitative computed tomography (QCT). We conducted a randomized, placebo-controlled, dose-ranging trial at 45 academic centers with 31 sites participating in the substudy. Patients included 569 postmenopausal women with low bone mineral density; vBMD was assessed at the spine and hip in a subset of 314 women. Patients were treated for up to 12 months with open-label teriparatide 20 μg subcutaneously once daily or randomly assigned in a double-blind manner to ronacaleret 100 mg, 200 mg, 300 mg, or 400 mg once daily, alendronate 70 mg once weekly, or matching placebos. Ronacaleret increased spine integral (0.49% to 3.9%) and trabecular (1.8% to 13.3%) vBMD compared with baseline, although the increments were at least twofold lower than that attained with teriparatide (14.8% and 24.4%, respectively) but similar or superior to that attained with alendronate (5.0% and 4.9%, respectively). There were small non-dose-dependent decreases in integral vBMD of the proximal femur with ronacaleret (-0.1 to -0.8%) compared with increases in the teriparatide (3.9%) and alendronate (2.7%) arms. Parathyroid hormone (PTH) elevations with ronacaleret were prolonged relative to that seen historically with teriparatide. Ronacaleret preferentially increased vBMD of trabecular bone that is counterbalanced by small decreases in BMD at cortical sites. The relative preservation of trabecular bone and loss at cortical sites are consistent with the induction of mild hyperparathyroidism with ronacaleret therapy. © 2012 American Society for Bone and Mineral Research.
Engelke K.,SYNARC Inc. |
Engelke K.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Nagase S.,ONO PHARMA UK LTD |
Fuerst T.,SYNARC Inc. |
And 5 more authors.
Journal of Bone and Mineral Research | Year: 2014
ONO-5334 (Ono Pharmaceutical Co., Ltd., Osaka, Japan) inhibits cathepsin K and has been shown to increase areal bone mineral density (BMD) at the hip and spine in postmenopausal osteoporosis. Quantitative computed tomography (QCT) allows the study of the cortical and trabecular bone separately and provides structural information such as cortical thickness. We investigated the impact of 2 years of cathepsin K inhibition on these different bone compartments with ONO-5334. The clinical study was a randomized, double-blind, placebo, and active controlled parallel group study conducted in 13 centers in six European countries. The original study period of 12 months was extended by another 12 months. A total of 147 subjects (age 55-75 years) of the QCT substudy who participated in the extension period were included. Subjects had been randomized into one of five treatment arms: placebo; ONO-5334 50 mg twice per day (BID); ONO-5334 100 mg once daily (QD); ONO-5334 300 mg QD; or alendronate 70 mg once weekly (QW). QCT was obtained to evaluate bone structure at the lumbar spine and proximal femur. After 24 months ONO-5334 showed statistically significant increases versus placebo for integral, trabecular, and cortical BMD at the spine and the hip (for ONO-5334 300 mg QD, BMD increases were 10.5%, 7.1%, and 13.4% for integral, cortical, and trabecular BMD at the spine, respectively, and 6.2%, 3.4%, and 14.6% for integral, cortical, and trabecular total femur BMD, respectively). Changes in cortical and trabecular BMD in the spine and hip were similar for alendronate as for ONO-5334. Integral volume did not demonstrate statistically significant changes under ONO-5334 treatment, thus there was no evidence of periosteal apposition, neither at the spine nor at the femur. Cortical thickness changes were not statistically significant for ONO-5334 in the spine and hip, with exception of a 2.1% increase after month 24 in the intertrochanter for ONO-5334 300 mg QD. Over 2 years ONO-5334 showed a statistically significant and persistent increase of trabecular and integral BMD at the spine and the hip. Cortical BMD also progressively increased but at a lower rate. Changes in bone size and of periosteal apposition were not observed. © 2014 American Society for Bone and Mineral Research.
Brixen K.,University of Southern Denmark |
Chapurlat R.,University of Lyon |
Cheung A.M.,University of Toronto |
Keaveny T.M.,University of California at Berkeley |
And 9 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013
Context: Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD)in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys. Objective: The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine. Design: This was a randomized, double-blind, 2-year trial. Setting: The study was conducted at a private or institutional practice. Participants: Participants included 214 postmenopausal women with low areal BMD. Intervention: The intervention included odanacatib 50 mg or placebo weekly. Main Outcome Measures: Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured. Results: Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P<.001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P<.001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P<.001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P<.001 at 24 months). Adverse experiences were similar between groups. Conclusions: Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine. Copyright © 2013 by The Endocrine Society.