Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasms

Diseases and Abnormalities at or Before Birth

Gland and Hormone Related Diseases

Rare Diseases

Syndrome

Proteinuria

Nephrotic Syndrome

Nephrosis

Wilms Tumor

Denys-Drash Syndrome

Frasier Syndrome

Kidney Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Neoplasms by Histologic Type

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Disorders of Sex Development

Disorder of Sex Development, 46,XY

Congenital Abnormalities

Urogenital Abnormalities

Gonadal Disorders

Endocrine System Diseases

Kidney Failure, Chronic

Renal Insufficiency

Renal Insufficiency, Chronic

Chronic Disease

Disease Attributes

Wilms' Tumor

Chronic Graft Versus Host Disease

Anja Lehnhardt, MD

The Wilms' tumor suppressor gene 1 (WT1) encodes for a transcription factor which plays an important role during urogenital development. Patients carrying a WT1 germline mutation show symptoms like proteinuria, Wilms tumors, genital malformations and kidney failure. Milder variants are possible and classification is not always possible. In this registry we are collecting detailed clinical data of affected individuals to establish genotype-phenotype correlations with the greater goal to optimize patient care.

The Wilms' tumor suppressor gene 1 (WT1) encodes for a transcription factor which plays an important role during urogenital development. Patients carrying a WT1 germline mutation show symptoms like proteinuria, Wilms tumors, genital malformations and kidney failure, which usually occur in early childhood. Milder variants are possible and classification as one of the three rare syndromes associated with WT1 mutations (Denys-Drash syndrome, Frasier syndrome or WAGR syndrome) is not always possible. In this registry we are collecting detailed clinical data of affected individuals to establish genotype-phenotype correlations with the greater goal to optimize patient care.

Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases

Registry for Patients With WT1 Mutation Associated Diseases

Universitätsklinikum Hamburg-Eppendorf

Musculoskeletal Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Wounds and Injuries

Digestive System Diseases

Nutritional and Metabolic Diseases

Infections

Neoplasm Metastasis

Arthritis

Arthritis, Rheumatoid

Hyperthermia

Gastrointestinal Diseases

Amyloidosis

Fever

Brucellosis

Familial Mediterranean Fever

Hereditary Autoinflammatory Diseases

Neoplastic Processes

Proteostasis Deficiencies

Metabolic Diseases

NC-503 (Anti-amyloidotic (AA) Agent)

The main objective of this study is to evaluate the safety and efficacy of NC-503 compared to placebo in patients with secondary (AA) amyloidosis using a composite assessment of clinical improvement/worsening of both renal and gastrointestinal functions.

AA amyloidosis is associated with chronic inflammatory conditions (rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease), chronic infection (tuberculosis, osteomyelitis), and Familial Mediterranean Fever. Rheumatoid arthritis is the major cause of AA amyloidosis in Western Europe and North America. The most common clinical feature of AA amyloidosis is renal dysfunction manifested as nephrotic-range proteinuria or renal insufficiency at the time of diagnosis. End-stage renal failure is the cause of death in 40-60% of cases. Gastrointestinal involvement is also frequent and is usually manifested as chronic diarrhea, body weight loss and malabsorption. Enlargement of the liver and spleen may also occur in some patients. The median survival time from diagnosis varies from 2 to 8 years depending on the stage of the disease at time of diagnosis. The goal of the current therapy in AA amyloidosis is the control of the associated disease. However, the current approaches for the treatment of AA amyloidosis are unspecific, toxic, invasive, and not sufficiently effective in many cases. NC-503 was specifically designed to compete with the naturally occurring sulfated GAGs for the binding to amyloidogenic precursor proteins, and to inhibit amyloid deposition into tissues. The proposed therapy with NC-503 is based on the prevention of the amyloid fibril formation. The objective of this clinical phase II/III study is to determine the efficacy and safety of NC-503 compared to a placebo in patients suffering from secondary (AA) amyloidosis by the assessment of clinical improvement/ worsening of both renal and gastrointestinal functions.

Study of the Safety and Efficacy of NC-503 in Secondary (AA) Amyloidosis

A Phase II/III Study of the Safety and Efficacy of NC-503 in Patients Suffering From Secondary (AA) Amyloidosis

FDA Office of Orphan Products Development

Bellus Health Inc. - a GSK company

Blood and Lymph Conditions

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Osteoporosis

Fractures, Bone

Rheumatic Diseases

Collagen Diseases

Fractures, Compression

Lymphoma

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Diseases

Bone Diseases, Metabolic

Connective Tissue Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

All Drugs and Chemicals

Glucocorticoids

* Juvenile Idiopathic Arthritis (JIA)
* Systemic Lupus Erythematosis
* Juvenile Dermatomyositis
* Scleroderma
* Overlap Syndromes
* Sjogren's syndrome
* Sarcoidosis
* Systemic Vasculitis (excluding Kawasaki's disease and Henoch-Schonlein Purpura)
* Systemic vasculitis as defined by the Chapel Hill Concensus Conference on Nomenclature. Other forms of systemic vasculitis, including Giant cell (temporal) arteritis, Takayasu's arteritis, Polyarteritis nodosa, Wegener's granulomatosis, Churg-Strauss syndrome, Microscopic polyangiitis, Essential cryoglobulinemic vasculitis, Cutaneous leukocytoclastic angiitis, Behcet's disease, Other vasculitis
* Other rheumatic disease

Nephrotic syndrome will be classified according to the following categories:

Idiopathic nephrotic syndrome, without renal biopsy histology, presumed minimal change disease (MCD), Focal segmental glomerulosclerosis (FSGS), confirmed on biopsy, Minimal change disease, confirmed on biopsy Nephrotic syndrome with Henoch-Schonlein Purpura (HSP).

Leanne M Ward, MD FRCPC

To determine the magnitude and rate of bone mass deficits following initiation of glucocorticoid therapy for the treatment of pediatric leukemia, rheumatic conditions and nephrotic syndrome, we propose a 6 year, prospective study in 12 academic, tertiary care centres across Canada.

The investigators hypothesize that glucocorticoid-treated children with leukemia, rheumatic conditions and nephrotic syndrome will fail to accrue bone mass at a normal rate, and that deficits in mineral accrual will occur in a glucocorticoid dose- and duration-dependent fashion. We also hypothesize that the fracture incidence will increase with concomitant reductions in bone mass.

Leukemia and Bone Morbidity Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with an overall survival rate now exceeding 70%. As such, there is an increasing population of survivors who are at risk for long-term sequelae of childhood leukemia, including osteoporosis. In Canada, there are approximately 250 new cases of childhood ALL diagnosed per year. All children in Canada undergoing therapy for the treatment of ALL in tertiary care pediatric hospitals will receive high dose glucocorticoids as per one of three ALL protocols (the Children's Cancer Group protocol, the Pediatric Oncology Group protocol, or the Dana Farber Cancer Institute Consortium protocol), depending upon the standard of care at a given institution. Musculoskeletal pain and gait abnormalities have been reported in one third of children with ALL at diagnosis, a sub-set of whom also demonstrate fractures. Radiographs of painful regions show metaphyseal lucencies, sclerotic lesions and sites of periosteal reaction in many of the patients with bone pain at presentation. Lumbar spine areal bone mineral density (BMD) is reduced at diagnosis, while total body and volumetric BMD are within the normal range. Several groups have reported significant loss of bone mass during therapy for ALL, while studies of bone mass restitution following chemotherapy have led to inconsistent results. The most rapid reductions in bone mass have occurred in the first 6-8 months of therapy, similar to the observed glucocorticoid effect on bone in adults. Fractures have been present in as many as 13% of children at diagnosis, rising to 39% during chemotherapy. In addition to glucocorticoids, a number of other mechanisms have been proposed for the skeletal morbidity in ALL, including infiltration of bone by leukemic cells, paraneoplastic factors, other medications, physical inactivity, cranial irradiation, inadequate nutrition and disordered mineral metabolism.

Rheumatic Conditions and Bone Morbidity Rheumatic diseases of childhood, including juvenile rheumatoid arthritis, systemic lupus erythematosis and juvenile dermatomyositis, are well-known to be associated with compromised skeletal health. Of these, juvenile rheumatoid arthritis has been evaluated the most extensively. Significant reductions in bone mass have been documented in a number of studies of pediatric patients with chronic rheumatic disease, and atraumatic fractures have been noted at an early age. Active arthritis may affect bone metabolism in areas adjacent to affected joints ("periarticular osteopenia"), and at more distant sites including the radius, spine, and femoral neck. In a recent study of pediatric patients with reductions in bone mass secondary to chronic rheumatic disease, 8/38 (21%) of patients had fragility fractures, primarily of the vertebrae. Similar to other osteoporotic conditions due to chronic illness, the pathogenesis of the bone morbidity in these cases is multi-factorial, with disease activity, muscle disease, physical inactivity, nutritional status and medical therapy playing significant roles. However, as in leukemia, glucocorticoid use has emerged as one of the strongest determinants of skeletal morbidity during treatment for juvenile rheumatoid arthritis and systemic lupus erythematosis. The role of glucocorticoids in bone morbidity associated with pediatric rheumatic diseases such as juvenile dermatomyositis and vasculitides has not been determined.

Nephrotic Syndrome and Bone Morbidity Childhood nephrotic syndrome is an idiopathic disorder characterized by proteinuria, hypoproteinemia, edema and hyperlipidemia. The incidence of the syndrome varies between 1:15,000 to 1:50,000. Following the introduction of glucocorticoid therapy in the 1970's, the mortality from nephrotic syndrome decreased dramatically over the ensuing 15 years, from 35 to 3 per cent. The vast majority of patients with nephrotic syndrome have steroid-responsive disease. In Canada, the standard of care for children with their first episode of nephrotic syndrome is high-dose glucocorticoid therapy for 6 weeks, followed by gradual tapering over the next three to seven months. Only one-third of patients will enter into permanent remission with this regime, while another third will require pulse steroid therapy for up to six weeks' duration at infrequent intervals throughout the growing years. The final third of patients will either require frequent courses of pulse glucocorticoid therapy or chronic steroid administration in order to achieve remission. Children with nephrotic syndrome are typically well-nourished, fully ambulatory, and otherwise well between episodes. Furthermore, their treatment regime is more likely to be characterized by glucocorticoid therapy alone, compared to the polytherapy that is required for the treatment of leukemia and rheumatic conditions. As such, the greater homogeneity of the nephrotic syndrome population allows for a more "pure" assessment of glucocorticoid effect on pediatric bone. Small studies have demonstrated reductions in bone mass by dual energy x-ray absorptiometry (DXA) and an increase in biochemical markers of bone resorption among young, glucocorticoid-treated patients with nephrotic syndrome. Tenbrock et al. recently showed by peripheral quantitative computed tomography that 16 children with nephrotic syndrome, all previously treated with glucocorticoids, had reductions in cortical area at the distal radius, which correlated with reductions in grip strength. The fracture rate among children with nephrotic syndrome is presently unknown. Among adults with nephrotic syndrome, high-dose glucocorticoid administration led to rapid bone loss in the first few months of therapy, raising the question whether preventive therapy should be initiated in such adults after three months of glucocorticoid use, if measures of bone mass have fallen significantly below baseline.

Steroid-Induced Osteoporosis in the Pediatric Population - Canadian Incidence Study

Steroid-Induced Osteoporosis in the Pediatric Population - Canadian Incidence Study (STOPP-CIS)

We will determine the magnitude and rate of total body, hip and lumbar spine bone mass deficits following initiation of glucocorticoid therapy, in relation to glucocorticoid dose and duration, among children with leukemia, rheumatic conditions and nephrotic syndrome. The longitudinal pattern of deficits (or gains) in bone mass will be determined for each disease state by plotting bone mass measurements taken at 6 month intervals throughout the study, with an additional 3 month measurement being recorded for patients with nephrotic syndrome.

To identify whether a glucocorticoid threshold dose exists for each of the three disease categories, above which significant deficits in bone mass are likely to occur.

To assess the frequency of atraumatic fractures in relation to glucocorticoid dose and duration for each of the three chronic illnesses.

To determine the fracture risk associated with a given reduction in bone mass from baseline, for each of the three chronic diseases.

To determine the magnitude of bone mass restitution when glucocorticoid therapy is withdrawn, and to evaluate whether recovery is age- and/or pubertal stage-dependent.

To investigate the relationship between handedness and lateralization of bone density.

Canadian Institutes of Health Research (CIHR)

Children's Hospital of Eastern Ontario

Director, Pediatric Bone Health Clinical and Research Programs

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases	NCT01252901	Denys-Drash Syn... Frasier Syndrom... Nephrotic Syndr... Wilms Tumor		-	Universitätsklinikum Hamburg-Eppendorf
Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases	NCT01252901	Denys-Drash Syn... Frasier Syndrom... Nephrotic Syndr... Wilms Tumor		-	Universitätsklinikum Hamburg-Eppendorf
Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases	NCT01252901	Denys-Drash Syn... Frasier Syndrom... Nephrotic Syndr... Wilms Tumor		-	Universitätsklinikum Hamburg-Eppendorf
Study of the Safety and Efficacy of NC-503 in Secondary (AA) Amyloidosis	NCT00035334	Secondary (AA) ... Rheumatoid Arth... Nephrotic Syndr... Familial Medite... Kidney Diseases Gastrointestina...	NC-503 (Anti-am...	18 Years -	Bellus Health Inc. - a GSK company
Steroid-Induced Osteoporosis in the Pediatric Population - Canadian Incidence Study	NCT01663129	Acute Lymphobla... Nephrotic Syndr... Rheumatism		1 Month - 16 Years	Children's Hospital of Eastern Ontario
Steroid-Induced Osteoporosis in the Pediatric Population - Canadian Incidence Study	NCT01663129	Acute Lymphobla... Nephrotic Syndr... Rheumatism		1 Month - 16 Years	Children's Hospital of Eastern Ontario

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