HORIZON SCANNING: PAEDIATRIC RHEUMATOLOGY UPATE SEPTEMBER 2011

Transcription

1 HORIZON SCANNING: PAEDIATRIC RHEUMATOLOGY UPATE SEPTEMBER 2011 The object of these Horizon Scanning reports is to highlight recently completed and ongoing clinical trials, research recommendations and new and emerging health technologies. After feedback from a pilot Horizon Scanning exercise and following consultation with the MCRN/ARC Paediatric Rheumatology CSG lead, these Horizon Scanning reports only highlight ongoing clinical trials or those completed since This follow up report includes trials registered since February 2011 for seven Topic Specific Groups (TSGs): Bone Health; Juvenile Dermatomyositis; Juvenile- Idiopathic Arthritis and JIA-associated Uveitis; Juvenile-onset Systemic Lupus Erythematosus; Noninflammatory Musculoskeletal Disorders; Scleroderma and Vasculitis. Details of all material included in this report are shown in the appendix, sorted according to TSG. Further details of each study can be obtained via the links given to the relevant webpage. CONTENTS SEARCH METHODOLOGY 2 RESULTS 3 ABBREVIATIONS 4 APPENDIX: CLINICAL TRIALS 5 A1. Bone Health. 5 A1a: Calcinosis, Hyper- & Hypo-Calcaemia 5 A1b: Dysplasia & McCune Albright syndrome 5 A1c: Osteogenesis imperfecta 6 A1d: Osteopetrosis 6 A1e: Osteoporosis & Osteopenia 7 A1f: (Juvenile) Paget s disease 8 A1g: Rickets & Hypophophatasia 8 A2. Juvenile Dermatomyositis. 8 A3. Juvenile Idiopathic Arthritis and JIA-associated Uveitis 9 A4. Juvenile-onset Systemic Lupus Erythematosus.. 11 A5. Non-inflammatory Musculoskeletal Disorders.. 11 A5a: Chronic pain syndrome, Complex regional pain syndrome & Fibromyalgia 11 A5b: Hypermobility, Joint hypermobility syndrome & ehlers-danlos 12 A6. Scleroderma.. 13 A7. Vasculitis Written by Nadia Corp for Arthritis Research UK 2011

2 SEARCH METHODOLOGY Databases Searched Clinical trials databases: MetaRegister of Clinical Trials (active registers); ClinicalTrials.gov; UKCRN Portfolio Database; Australia and New Zealand Horizon Scanning Network (ANZHSN); MRC Clinical Trials Unit; Nederlands Trials Register; German Clinical Trials Register; University Hospital Medical Information Network (UMIN); Japan Medical Association Center for Clinical Trials Register (JMA- CTR); Japan Pharmaceutical Information Center Clinical Trials Register. Keywords searched Keywords and phrases were used separately or in combination; truncation was used where possible/applicable. Bone health: Calcinosis, Hypercalc[a]emia, Hyperphosphatasemia, Hypocalc[a]emia, Hypophosphatasia, Juvenile Paget s disease, McCune Albright syndrome, Osteop[a]enia; Osteogenesis imperfecta, Osteopetrosis, Osteoporosis (juvenile idiopathic, glucocorticoidinduced/steroid-induced, disuse, pseudoglioma syndrome), Polyostotic fibrous dysplasia, Rickets (vitamin D deficiency, hypophosphataemic; pseudo-d deficiency; hereditary vitamin D resistant rickets), Skeletal dysplasia; Fracture (spinal/vertebral); Dermatomyositis; JIA, Juvenile idiopathic arthritis, juvenile rheumatoid arthritis, juvenile chronic arthritis, Oligoarticular juvenile arthritis, Pauciarticular juvenile arthritis, Polyarticular juvenile arthritis, Still's disease, JIA associated uveitis, Idiopathic uveitis, Autoimmune uveitis; [Juvenile-onset] systemic lupus erythematosus, SLE, lupus nephritis; Non-inflammatory: Chronic pain syndrome, Complex regional pain syndrome, Ehlers-Danlos, Fibromyalgia, Hypermobility, Joint Hypermobility Syndrome; Scleroderma, Systemic sclerosis; Vasculitis, Kawasaki Disease, Mucocutaneous Lymph Node Syndrome, Behcet s Syndrome, Wegener s Granulomatosis, Microscopic Polyangiitis (MPA), Microscopic Polyarteritis, Polymyalgia rheumatic, Renal limited vasculitis, Cryoglobulinaemic vasculitis, Cogan s syndrome, Takayasu s Arteritis, Churg-Strauss Syndrome, Polyarteritis Nodosa, ANCA associated vasculitis, Henoch Schonlein purpura;, ren, hood, Adolescent, Juvenile, Paediatric. limits Trials registered since February are included in the feedback. Additional search terms, notably osteopenia and vertebral/spinal fracture, are included in the Bone Health TSG scan, therefore, any corresponding clinical trials ongoing or completed since January 2009 are included in the feedback. Age limits Studies involving individuals of 18 2 of age and under were included in the report. 1 The German Clinical Trials Registry was inaccessible for the last horizon scan in February 2011, therefore trails registered since July 2010 are included in this update. 2 with the exclusion of studies where the lowest age limit is 18 of age. 2

3 RESULTS A total of 37 completed or ongoing clinical trials were identified across the seven topic areas included within paediatric rheumatology. These are tabulated in the appendix divided into sections: A1: Bone Health (n = 9); A2: Dermatomyositis (n = 4); A3: Juvenile idiopathic arthritis and JIA-associated uveitis (n = 8); A4: Juvenile-onset systemic lupus erythematosus (n = 2); A5: Non-inflammatory (n = 6); A6: Scleroderma (n = 5); A7: Vasculitis (n = 3). For clarity each section is subdivided according to type of intervention: behavioural, education & exercise including physiotherapy; device; drug including biologics; procedure; other interventions including CAM; and no intervention, observational. Within each division, studies have been classified according to age group involved: 18 (child) or all age groups (child and adult (including senior)) or age group unknown, and then arranged in descending chronological order of anticipated completion-date. (Trials where the end date was not specified are included based update the last update status e.g. recruitment complete etc, and follow-up time points if applicable.) Unless otherwise stated in the table trials involve participants of both genders. Each clinical study has a weblink which can be followed for further details. Where there was uncertainty regarding whether a study should be included or not (usually due to its focus), the decision aired on the side of caution and the trial was included in the feedback. 3

4 ABBREVIATIONS ANCA Comp CT F-only Grp JDM MTX n N/K RCT ruit SLE Adult (18-65 ) Anti-neutrophilic Cytoplasmic Antibody (birth-17 ) Completed Controlled trial Clinical Trials Identifier Females only Group Juvenile Dermatomyositis Methotrexate Enrollement Not known Randomized controlled trial. ruiting ruitment ior (66+ ) Systemic Lupus Erythematosus 4

5 FULL TEXT APPENDIX SECTION B: CLINICAL TRIALS Clinical trials identity number (): Prefix of NCT denotes National Clinical Trials Identifier; ISRCTN - International Standard Randomized Controlled Trial Number; UKCRN UK Clinical Research Network; ACTRN Australian New Zealand Clinical Trials Registry; NTR Nederland Trial Register; DRK German clinical Trials Register; UMIN University Hospital Medical Information Network; JMA - Japan Medical Association Center for Clinical Trials Register; JapicCTI - Japan Pharmaceutical Information Center Clinical Trials Identifier. Note: Where no end date was given the following were used: completion date for primary outcome measure italics; last update preceeded with a?; start date + final timepoint of outcomes preceeded with a >. A1: BONE HEALTH A1A: CALCINOSIS, HYPER- & HYPO-CALCAEMIA No new clinical trials identified A1B: DYSPLASIA & MCCUNE-ALBRIGHT SYNDROME 18 Multicentre randomised controlled trial of minimally-invasive surfactant therapy in preterm infants weeks gestation on continuous positive airway pressure RCT (placebo), efficacy study ACTRN Continuous positive airway pressure and poractant surfactant 200 mg.kg -1 ; Continuous positive airway pressure Bronchopulmonary dysplasia; Neonatal respiratory distress syndrome Not yet Sept-11 > Menzies hours Sept-11 Research Institute; University of Tasmania =

6 Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants. RCT (placebo), efficacy study NTR2768 Hydrocortisone Preterm neonates, ventilator dependent at 7-14 days, Bronchopulmonary dysplasia Active 400 Preterm infant Sept-11 Sept-16 Academic Medical Center (AMC), Netherlands ew.asp?tc=2768 Procedures 18 Is bias gas flow in ventilated preterm babies related to lung injury and risk of bronchopulmonary dysplasia? RCT (active), efficacy study ACTRN Conventional ventilation via ETT at a bias gas flow of 4 L.min -1 ; Conventional ventilation via ETT at a bias gas flow of 10 L.min -1 Bronchopulmonary dysplasia; ventilatorinduced lung injury Active days Sept-11 > University of Sept-13 Auckland; Auckland City Hospital = No intervention, observational All age groups Energy Expenditure and Body Composition in Pseudohypoparathyroidism 1a Cross-sectional cohort study NCT Pseudohypoparathyr oidism Type 1A; Albright Hereditary Osteodystrophy Jun-11 Jun-12 ren's Hospital of Philadelphia A1C: OSTEOGENESIS IMPERFECTA No new clinical trials identified A1D: OSTEOPETROSIS No new clinical trials identified 6

7 A1E: OSTEOPOROSIS & OSTEOPENIA All age groups Effects of Anorexia Nervosa on Peak Bone Mass Phase III: RCT (placebo), safety/efficacy study NCT RhIGF-1 with transdermal 17-beta estradiol; Placebo and transdermal 17- beta estradiol Anorexia Nervosa 136 F- only Feb-11 Dec-17 Massachusetts General Hospital; The Hospital for Sick ren The Effect of Vitamin D Supplementation on Calcium Excretion in Thalassemia: a Dose Response Study Phase IV: RCT (placebo), safety/efficacy study NCT Vitamin D3; Placebo Thalassemia Major Not yet Jun-11 Dec-14 Weill Medical College of Cornell University Age group unknown Examination for the effect of combination therapy using SERM and Eldecalcitol for the patients with osteoporosis RCT (active), safety/efficacy study UMIN Raloxifene; Raloxifene & Alfacalcidol; Raloxifene & Eldecalcitol Osteoporosis 150 F- only 50? >Jul-11? Juntendo >Jul-11 University s&type=summary&recptno=r &l anguage=e No intervention: observational Age group unknown Analysis of abnormalities of human chondrocyte and bone cell signalling pathways in the pathogenesis of osteoarthritis and osteoporosis. UKCRN ID 5547 Osteoarthritis; Osteoporosis Active 500 N/K N/K Dec-11 NHS Lothian; University of Edinburgh il.aspx?studyid=5547 7

8 A1F: (JUVENILE) PAGET S DISEASE No new clinical trials identified A1G: RICKETS & HYPOPHOPHATASIA No intervention: observational 18 Epidemiologic Study of the Natural History of Infantile-Onset Hypophosphatasia (HPP) Retrospective, cohort study NCT Hypophosphatasia Aug-11 Dec-13 Enobia Pharma A2: JUVENILE DERMATOMYOSITIS All age groups Investigation in Myositisassociated Pneumonitis of Tacrolimus Prednisolone And Concomitant Tacrolimus Phase II/III: Controlled trial (historical), safety/efficacy study JMA-IIA00012 Interstitial pneumonitis associated with polymyositis/ dermatomyositis Active to <75 Jul-07 Feb-10 IMPPACT study central office (Japan) pp/jmactrs06/jmactrs06.aspx?seqno =322 8

9 No intervention: observational Age group unknown JDCBS: Juvenile Dermatomyositis Cohort Biomarker Study and Repository (UK & Ireland) Cohort study UKCRN ID 7723 Biopsy score tool study in JDM Pilot, feasibility study UKCRN ID 6620 Autoantigens in juvenile myositis UKCRN ID 4982 Juvenile Dermatomyositis Juvenile Dermatomyositis Juvenile Dermatomyositis Ongoing 500 N/K N/K Nov-19 Great Ormond Street Hospital for ren Ongoing 100 N/K N/K Jun-12 Great Ormond Street Hospital for ren il.aspx?studyid= il.aspx?studyid=6620 Comp 400 N/K N/K Dec-08 Bath Royal National Hospital il.aspx?studyid=4982 for Rheumatic Diseases A3: JUVENILE IDIOPATHIC ARTHRITIS AND JIA-ASSOCIATED UVEITIS 18 Sycamore: Randomised controlled Adalimumab & trial of the clinical effectiveness, MTX; MTX SafetY and Cost effectiveness of alone; Placebo Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis Phase II/III: RCT (placebo), safety/efficacy study UKCRN ID Biologics for ren with Rheumatic Diseases - The Extended Biologics Study UKCRN ID 7725 JIA (all subgroups that have uvietis) Not yet to 18 9 Biologic drugs JIA 500 <18 N/K N/K Oct-15 University Hospitals Bristol l.aspx?studyid=10320 NHS Foundation Trust Jan-15 University of Manchester l.aspx?studyid=7725

10 All age groups Extension Study Evaluating Etanercept Etanercept in 3 Subtypes of hood Arthritis Phase II/III: Single group assignment, safety study NCT Effect of Adalimumab for the Anti-tumor Treatment of Uveitis in Juvenile necrosis factor Idiopathic Arthritis alpha Phase II/III: RCT (placebo), efficacy monoclonal study antibody; NCT placebo Juvenile Idiopahtic Arthritis Uveitis; Juvenile Arthritis Not yet Oct-11 Jan-21 Pfizer Jun-11 Dec-14 Assistance Publique - Hôpitaux de Paris; Abbott Effect of Adalimumab for the Treatment of Uveitis in Juvenile Idiopathic Arthritis Phase II/III: RCT (placebo), efficacy study NCT No intervention: observational 18 An Observational Registry of Abatacept in Patients With Juvenile Idiopathic Arthritis NCT Pharmacovigilance in Juvenile Idiopathic Arthritis Patients Treated With Biologic Agents and/or Methotrexate NCT Prevalence of Musculoskeletal Disability in Down's syndrome UKCRN ID Juvenile Idiopathic Arthritis Juvenile Idiopathic Arthritis Down s syndrome; Musculoskeletal abnormality, in particular: hypermobility or inflammatory arthritis. Not yet Not yet Active Jul-11 Jun-28 Bristol-Myers Squibb Jul-11 Mar-21 Istituto Giannina Gaslini; Members of the PRINTO network (PRINTO at N/K Mar-12 NHS Greater Glasgow & l.aspx?studyid=10154 Clyde Age group unknown Special Investigation (All Case Survey) in Patients With Juvenile Idiopathic Arthritis NCT Arthritis, Juvenile Rheumatoid 100 Aug-11 Jan-14 Abbott 10

11 A4: JUVENILE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS All age groups A Study to Evaluate the Safety and Efficacy of Tacrolimus for Lupus Tacrolimus Lupus Nephritis 1400 Nephritis Under Actual Use Situations NCT Jan-07 Jan-20 Astellas Pharma Inc No intervention, observational Age groups unknown Generation of Anti-Cytokine Antibodies from B Cells of Patients with Systemic Lupus Erythematosus. Observational study NTR 2912 SLE 10 N/K May-11 Dec-11 Academic Medical Center (AMC), The Netherlands ew.asp?tc=2912 A5: NON-INFLAMMATORY MUSCULOSKELETAL DISORDERS A5A: CHRONIC PAIN SYNDROME, COMPLEX REGIONAL PAIN SYNDROME & FIBROMYALGIA 18 Long-Term Safety and Efficacy Study of Milnacipran in Pediatric Patients With Primary Fibromyalgia Phase II: Single group assignment, safety/efficacy study NCT Milnacipran Primary Fibromyalgia Syndrome Apr-11 May-14 Forest Laboratories; Cypress Bioscience, Inc.

12 Safety and Efficacy of Milnacipran in Pediatric Patients With Primary Fibromyalgia Phase II: RCT (placebo), safety/efficacy study NCT Milnacipran; Placebo Primary Fibromyalgia Syndrome Apr-11 May-13 Forest Laboratories; Cypress Bioscience, Inc. A5B: HYPERMOBILITY, JOINT HYPERMOBILITY SYNDROME & EHLERS-DANLOS No intervention, observational 18 Prevalence of Musculoskeletal Disability in Down's syndrome UKCRN ID Down s syndrome; Musculoskeletal abnormality, in particular: hypermobility or inflammatory arthritis. Active N/K Mar-12 NHS Greater Glasgow & Clyde il.aspx?studyid=10154 All age groups Head Circumference Growth in ren With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life Retrospective, case-only study NCT Ehlers Danlos Syndrome; External Hydrocephalus; Dysautonomia; Postural Orthostatic Tachycardia Syndrome; Venous Insufficiency 25 5 May-11 Nov-11 Genetic Disease Investigators Age group unknown National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions NCT Marfan Syndrome; Turner Syndrome; Ehlers-Danlos Syndrome; Loeys-Dietz Syndrome and other genetic conditions Nov-07 Sep-15 National Heart, Lung & Blood Institute; National Institute of Arthritis & Musculoskeletal & Skin Diseases 3 FBN1, TGFBR1, TGFBR2, ACTA2 or MYH11 Genetic Mutation; Bicuspid Aortic Valve Without Known Family History; Bicuspid Aortic Valve With Family History; Bicuspid Aortic Valve With Coarctation; Familial Thoracic Aortic Aneurysm and Dissections; Shprintzen-Goldberg Syndrome; Other Aneurysms and Dissections of the Thoracic Aorta Not Due to Trauma, <50yo; Other Congenital Heart Disease 12

13 Vascular Fundus Changes in Patients With High Probability of Chronic Cerebrospinal Venous Insufficiency (CCSVI) Cross-sectional case control study NCT Ehlers-Danlos Syndrome; Multiple Sclerosis 60 May-11 Nov-11 Genetic Disease Investigators; Optos plc A6: SCLERODERMA Age group unknown Post Marketing Surveillance Study of Cuprimine NCT Cuprimine (penicillamine) Scleroderma Active not N/K? Jun 11? Jun 11 Merck Procedure All age groups High-Dose Cyclophosphamide and Anti-Thymocyte Globulin Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Systemic Scleroderma Phase II: Single group assignment, efficacy study NCT Peripheral blood stem cell transplantation; cyclophosphamide; anti-thymocyte globulin; filgrastim; Autologous hematopoietic stem cell transplantation Systemic Scleroderma Not yet 30 <70 Aug-11 Sep-19 Fred Hutchinson Cancer Research Center; National Cancer Institute (NCI) 13

14 No intervention, observational Age group unknown Validation of potential markers of disease in systemic sclerosis Crosssectional study UKCRN ID Focus On Capillaroscopic Ulcer index in Systemic sclerosis ISRCTN Validation of nailfold capillaroscopy in systemic sclerosis Cross-sectional study UKCRN ID Systemic Sclerosis; Undifferentiated connective tissue disease or Primary Raynaud's Phenomenon Systemic sclerosis Systemic Sclerosis; Undifferentiated connective tissue disease or Primary Raynaud's Phenomenon Active 280 N/K N/K Apr-17 Salford Royal NHS Foundation.aspx?StudyID=10851 Trust Active N/K Feb-11 Feb-13 Actelion Pharma Schweiz AG (Switzerland) Active 200 N/K N/K Dec-12 Salford Royal NHS Foundation.aspx?StudyID=10804 Trust 14

15 A7: VASCULITIS All age groups The Efficacy of Methylprednisolone Methylorednisolone; in the Treatment of Patients With Dextrose water 5% Ocular Involvement in Behcet's Disease Phase IV RCT (placebo), efficacy study NCT Behcet's Disease Feb-10 Aug-11 Tehran University of Medical Sciences No intervention, observational 18 A prospective outcome study on patients with profound combined immunodeficiency DRKS Research on the identification of the causative agent of the Kawasaki disease UMIN Common variable immunodeficiency with predominant immunoregulatory T-cell disorders Active Kawasaki disease Active 5 <3 Jul-11 > Jul-16 Centrum für chronische Immundefizienz Mar-11 Mar-15 Osaka Prefectural Institute of Public Health nid=trial.html&trial_id=drks &type=summary&recptno=r &lan guage=e 15