Clinical and Biochemical Factors Associated With Risk of Total Joint Replacement and Radiographic Progression in Osteoarthritis: Data From Two Phase III Clinical Trials
Objectives: Clinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but great vari…
Journal:
Authors:
- Bihlet A,
- Bjerre-Bastos JJ,
- Andersen JR,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
Multinutrient Supplementation Increases Collagen Synthesis during Early Wound Repair in a Randomized Controlled Trial in Patients with Inguinal Hernia.
BACKGROUND:
Inguinal hernia disease is associated with an imbalanced collagen metabolism. Surgical stress has a negative impact on nutrients important for collagen synthesis.
OBJECTIVE:
We hypothesized that supplementation with a combination of nutrients would enhance collagen biosynthesis in i…
Journal:
Authors:
- Kjaer M,
- Frederiksen AKS,
- Nissen NI,
- Willumsen N,
- Van Hall G,
- Jorgensen LN,
- Andersen JR,
- Årgen MS,
Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis.
BACKGROUND:
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee j…
Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Karsdal MA,
Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
Journal:
Authors:
- Bertelsen DM,
- Neergaard JS,
- Bager CL,
- Nielsen SH,
- Secher NH,
- Svendsen JH,
- Bihlet AR,
- Andersen JR,
- Karsdal MA,
- Christiansen C,
- Nielsen HB,
Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis
BACKGROUND:
Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinica…
Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Valter I,
- Karsdal MA,
- Hochberg MC,
Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study
The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are the key fac…
Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Kehlet SN,
- Hansen HB,
- Hansen G,
- Byrjalsen I,
- Alexandersen P,
- Lindgren LM,
- Bihlet AR,
- Riis BJ,
- Andersen JR,
- Qvist P,
- Karsdal MA,
- Christiansen C,
A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D
This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D …
Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Andersen JR,
- Bihlet AR,
- Russo LA,
- Alexandersen P,
- Valter I,
- Qvist P,
- Lau E,
- Riis BJ,
- Christiansen C,
- Karsdal MA,
- SMC021 investigators,
Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t…
Journal:
Authors:
- Karsdal MA,
- Michaelis M,
- Ladel C,
- Siebuhr AS,
- Bihlet AR,
- Andersen JR,
- Guehring H,
- Christiansen C,
- Bay-Jensen AC,
- Kraus VB,
The impact of clinical trial monitoring approaches on data integrity and cost-a review of current literature
PURPOSE:
Monitoring is a costly requirement when conducting clinical trials. New regulatory guidance encourages the industry to consider alternative monitoring methods to the traditional 100 % source data verification (SDV) approach. The purpose of this literature review is to provide an overview o…
Journal:
Authors:
Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD
Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development o…
Journal:
Authors:
- Bihlet A,
- Karsdal MA,
- Bay-Jensen AC,
- Read S,
- Kristensen JH,
- Sand JM,
- Leeming DJ,
- Andersen JR,
- Lange P,
- Vestbo J,
Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials
AIM:
The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.
METHODS:
We used data from three randomized phase I…
Journal:
Authors:
- Andersen JR,
- Byrjalsen I,
- Bihlet A,
- Kalakou F,
- Hoeck HC,
- Hansen G,
- Hansen HB,
- Karsdal MA,
- Riis BJ,
OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA
BACKGROUND/PURPOSE:
The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Art…
Journal:
Authors:
- Karsdal MA,
- Bihlet A,
- Byrjalsen I,
- Alexandersen P,
- Ladel C,
- Michaels M,
- Andersen JR,
- Riis BJ,
- Kraus V,
- Bay-Jensen AC,
- Christiansen C,
Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials
PURPOSE:
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural d…
Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Alexandersen P,
- Bihlet A,
- Andersen JR,
- Riis BJ,
- Bay-Jensen AC,
- Christiansen C,
- CSMC021C2301/1 investigators,
Impact of Source Data Verification on data quality in clinical trials: An empirical post-hoc analysis of three phase 3 randomised clinical trials
AIM:
The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.
METHODS:
We used data from three randomized phase I…
Journal:
Authors:
- Andersen JR,
- Byrjalsen I,
- Bihlet AR,
- Kalakou F,
- Hoeck HC,
- Hansen G,
- Hansen HB,
- Karsdal MA,
- Riis BJ,
Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis
CONTEXT:
Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1-34) or rhPTH(1-84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance.
OB…
Journal:
Authors:
- Henriksen K,
- Andersen JR,
- Riis BJ,
- Mehta N,
- Tavakkol R,
- Alexandersen P,
- Byrjalsen I,
- Valter I,
- Nedergaard BS,
- Teglbjaerg CS,
- Stern W,
- Sturmer A,
- Mitta S,
- Nino AJ,
- Fitzpatrick LA,
- Christiansen C,
- Karsdal MA,