View clinical trials related to Cushing Syndrome.
Filter by:This retrospective, multi-center, chart review study will collect patient data from medical charts of pediatric patients who have been treated with Korlym for Cushing's syndrome.
The purpose of this study is to follow participants with Cushing's syndrome during the course of their routine care and to form a data registry to study long term participant outcomes.
This is an observational, open, prospective multi-centre study designed to evaluate melatonin and cortisol circadian rhythm, immunological profile and anthropometric parameters in Cushing Syndrome patients during active Remission state.
This is a double-blind, randomized, placebo-controlled withdrawal and rescue/restoration study in subjects with endogenous Cushing's Syndrome (CS) previously treated with single-arm, open-label levoketoconazole that will assess efficacy, safety, tolerability, and pharmacokinetics of levoketoconazole.
Several studies have shown that lean mass, in particular muscle mass, is an excellent predictive survival factor in many diseases. A better knowledge of the mechanisms responsible for muscle atrophy and the identification of atrophic process markers are deeply needed for the development of new anti-atrophic therapies. Either as drugs used to treat several medical conditions or as endocrine hormones released in response to many stress situations (e.g., sepsis, cancer, insulinopenia…), glucocorticoids (GC) are recognized to play a major role in skeletal muscle atrophy. Indeed, the inhibition of GC action by a receptor antagonist (RU486) or by muscle-specific invalidation of the GC receptor inhibits the muscle atrophy in these stress situations. Therefore, all these data clearly indicate that GC play a major role in skeletal muscle atrophy observed in several conditions. Emerging evidence has revealed that the skeletal muscle has a secretory function. Human skeletal muscle secretome was first estimated at about 300 proteins by computational analysis and proteomic analysis have recently confirmed these results. Some of these secreted proteins, conceptualized as myokines, can act locally on muscle cells through autocrine/paracrine loops and on surrounding tissues such as muscle blood vessels or can be released into the blood stream to produce systemic effects. One prominent example is interleukin (IL)-6 which is released into circulation by contracting skeletal muscle and can regulate metabolic and inflammatory processes. As IL-6, several other potential myokines have been identified including IL-8, IL-15, insulin-growth factor I (IGF-I), follistatin-like 1 (FSTL1) or fibroblast-growth factor (FGF)-21. Moreover, secreted proteins may also reflected metabolic changes which take place in muscle cells. Indeed, myoblast differentiation is accompanied by dramatic changes in the secreted proteins profile as increased expression of Semaphorins, IGF-I, matrix metalloproteinase (MMP)-2 or Collagens. Thereby, the investigators hypothesized that skeletal muscle atrophy induced by GC is associated with specific alterations of the muscle secretome. The aim of this project is to identify the GC-induced changes in the secretome of human skeletal muscle cells in culture (in vitro approach) and to determine how these changes translate into the circulation of subjects exposed to high concentrations of GC (Cushing's syndrome) (in vivo approach). Characterization of these changes in human subjects should allow to better understand the cellular mechanisms involved in muscle atrophy and might lead to identify circulating biomarkers associated with skeletal muscle atrophy, as telopeptides are for bone tissue.
This is a prospective, multi-center, case-control study where neurocognitive function will be evaluated in 36 patients with Cushing syndrome (CS) and 36 controls matched for age, gender and education.
Osteoporosis induced by glucocorticoids excess constitutes the main cause of secondary osteoporosis. Most of data available are provided from cohort studies of patients treated by corticosteroids, affecting among 1% of population. In contrast, very few data on osteoporosis are available in the Cushing syndrome (CS), a rare disease affecting 1 or 2 million of inhabitants, and characterized by an endogen glucocorticoid excess production. This affection is responsable of frequent fractures, occuring in 30-60% of patients (vertebral asymptomatic in 50% of case, hip, ribs). Fractures occurs often frequently above the threshold usually used for osteoporosis (T-score<-2.5), most often in the range of osteopenia. These data suggest that surface bone density isn't sufficient to characterize bone fragility, architectural factors are probably involved, and should be evaluated. The specificity of osteoporosis induced by endogen glucocorticoids excess in comparison with osteoporosis induced by estrogenic deficiency in post-menopausal women is poorly known, especially in endogen glucocorticoid excess. A recent microarchitecture studies showed alterations of cortical compartment in patients with Cushing's syndrome, confirming by our preliminary preclinical data from a transgenic murin model of Cushing's syndrome. In these ten last years, new radiologic tools have been developped, and are able to evaluate bone architecture. The peripheral Quantitative Computed analyses the bone architecture with distinction between cortical and trabecular compartment. Therefore, we aim to determine the specificity of osteoporosis induced by glucocorticoids excess in comparison to post menopausal osteoporosis thanks to pQCT analysis.
Adrenocortical Carcinoma (ACC) is an extremely rare disease. Approximately 50% of ACC in adults are functioning leading to hormonal and metabolic syndromes. Cortisol hypersecretion (Cushing's syndrome) is the most common endocrine derangement at presentation. Moreover, hypercortisolism is one of the factors that negatively influence the outcome of patients with metastatic ACC. Abiraterone acetate (AA) is a prodrug of abiraterone, an irreversible inhibitor of 17α hydroxylase/C17, 20-lyase (cytochrome P450c17 [CYP17]).The inhibition of CYP17A1 blocks androgen and cortisol synthesis. AA has a pharmacodynamic potential to reduce cortisol excess and it has never been tested before in Cushing's syndrome. Thus, we decided to evaluate the activity of Abiraterone Acetate in the management of Cushing's syndrome in patients with adrenocortical carcinoma. The study is a phase II, non-randomized, open-label study with two different experimental sub-cohorts: Cohort 1: Patients locally advanced/metastatic ACC patients with uncontrolled Cushing's syndrome despite Mitotane +/- chemotherapy will be treated with single agent AA. In this cohort, Mitotane and chemotherapy will be interrupted and AA will be continued till progression and/or as long as the Cushing's syndrome is adequately controlled (ie until progression of Cushing's syndrome). Cohort 2: Mitotane-naïve patients with newly diagnosis of ACC associated with Cushing's syndrome not amenable to surgical resection with radical intent will be treated with single agent AA for 4 weeks followed by AA + Mitotane +/- first-line chemotherapy. In this cohort, AA in association with Mitotane will be administered for 3 months. If the primary endpoint is obtained before 1 month (i.e. 2 or 3 weeks from Abiraterone start), then Mitotane +/- chemotherapy can be started upon the clinician's decision.
Currently, 2-3% of the population of the United Kingdom and United States of America receive glucocorticoid therapy. Significant adverse effects are not confined to chronic use; recurrent short-course administration is associated with increased morbidity and mortality. The adverse metabolic features associated with glucocorticoid use include obesity, skeletal muscle myopathy, hypertension, insulin resistance and diabetes and are collectively termed 'iatrogenic Cushing's syndrome'. The efficacy of glucocorticoid therapy is not in doubt, but there are no interventions to reduce their metabolic consequences. Within metabolic tissues (liver, skeletal muscle, adipose), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid and therefore is able to tightly control the availability of glucocorticoids to activate the glucocorticoid receptor. In preclinical studies, the investigators have shown that 11β-HSD1 is critical in regulating the development of the adverse features associated with circulating glucocorticoid excess, endorsing our observations in a patient with Cushing's disease, who was protected from a classical phenotype due to a functional deficit in 11β-HSD1. This study is the first clinical evaluation of the impact of the selective 11β-HSD1 inhibitor, AZD4017, in healthy volunteers taking exogenous glucocorticoids (prednisolone). The investigators propose that in tissues expressing high levels of 11β-HSD1, prednisolone action will be amplified, driving adverse effects within these tissues and have hypothesized that AZD4017 in humans will reduce the adverse metabolic consequences of Prednisolone administration without compromise to its anti-inflammatory action. Our specific research objectives are: 1. To demonstrate the beneficial effect of the selective 11β-HSD1 inhibitor, AZD4017, upon the prednisolone-induced deterioration in metabolic phenotype, including glucose disposal and endogenous glucose production rates. 2. To determine the impact of AZD4017 on the anti-inflammatory actions of Prednisolone. 3. To identify the tissue-specific (skeletal muscle, adipose) mechanisms underpinning the response to Prednisolone therapy administered in conjunction with AZD4017. The investigators will perform a randomized, double-blind placebo controlled study to determine if co-administration of the selective 11β-HSD1 inhibitor, AZD4017, limits the adverse effects of short-course exogenous glucocorticoid administration. 32 healthy male volunteers will have detailed metabolic investigations including 2-step hyperinsulinaemic euglycaemic clamps (with stable isotope measurements of lipid and carbohydrate metabolism), as well as assessment of skeletal muscle forearm glucose uptake. All volunteers will then be treated with Prednisolone (20mg daily) and randomized to the co-administration of placebo or AZD4017. After 1 week of therapy, all investigations will be repeated. Our hypothesis is that the adverse metabolic effects of Prednisolone will be reduced by co-administration of AZD4017.
This is a Phase 2 multicenter, randomized, double-blind, placebo controlled study of ATR-101 to evaluate the efficacy and safety of orally-administered ATR-101 in adults with endogenous Cushing's syndrome. Following wash-out (if needed), all eligible subjects will enter an open-label intra-subject dose-escalation period of 8 weeks' duration, followed either by a double-blind randomized withdrawal period of 4 weeks' duration (if the subject meets randomization criteria) or by an additional open label dosing period of 4 weeks' duration (if the subject does not meet randomization criteria).It is anticipated that the overall duration of the study per subject will range from approximately 16-22 weeks.