11β-Hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial
Abstract Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hyp...
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| Published in | Brain communications Vol. 2; no. 1; p. fcz050 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Oxford University Press
2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2632-1297 2632-1297 |
| DOI | 10.1093/braincomms/fcz050 |
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| Abstract | Abstract
Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18–55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: −2.8, 95% confidence interval: −7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: −4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: −0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest.
Preclinical research highlighted the role of 11β-hydroxysteroid dehydrogenase type 1 inhibition in modulating intracranial pressure. We report the first phase II randomized clinical trial in idiopathic intracranial hypertension evaluating safety, tolerability, in vivo efficacy and initial clinical efficacy of a novel inhibitor of 11β-hydroxysteroid dehydrogenase type 1 to lower intracranial pressure in active idiopathic intracranial hypertension.
Graphical Abstract
Graphical Abstract |
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| AbstractList | Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18–55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: −2.8, 95% confidence interval: −7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: −4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: −0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest. Preclinical research highlighted the role of 11β-hydroxysteroid dehydrogenase type 1 inhibition in modulating intracranial pressure. We report the first phase II randomized clinical trial in idiopathic intracranial hypertension evaluating safety, tolerability, in vivo efficacy and initial clinical efficacy of a novel inhibitor of 11β-hydroxysteroid dehydrogenase type 1 to lower intracranial pressure in active idiopathic intracranial hypertension.
Graphical Abstract Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18-55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: -2.8, 95% confidence interval: -7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: -4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: -0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest.Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18-55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: -2.8, 95% confidence interval: -7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: -4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: -0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest. Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18-55 years with active idiopathic intracranial hypertension (>25 cmH O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m ] were randomized to AZD4017 ( = 17) or placebo ( = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH O) compared with placebo (31.3 cmH O), but the difference between groups was not statistically significant (mean difference: -2.8, 95% confidence interval: -7.1 to 1.5; = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: -4.3 cmH O (SD = 5.7); = 0.009] but not in the placebo group [mean change: -0.3 cmH O (SD = 5.9); = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure ( = 0.005, = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity . Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest. Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18–55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: −2.8, 95% confidence interval: −7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: −4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: −0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest. Abstract Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18–55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: −2.8, 95% confidence interval: −7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: −4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: −0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest. Preclinical research highlighted the role of 11β-hydroxysteroid dehydrogenase type 1 inhibition in modulating intracranial pressure. We report the first phase II randomized clinical trial in idiopathic intracranial hypertension evaluating safety, tolerability, in vivo efficacy and initial clinical efficacy of a novel inhibitor of 11β-hydroxysteroid dehydrogenase type 1 to lower intracranial pressure in active idiopathic intracranial hypertension. Graphical Abstract Graphical Abstract |
| Author | Gilligan, Lorna C Botfield, Hannah Mollan, Susan P Markey, Keira Stewart, Paul M Scotton, William Sinclair, Alexandra J Matthews, Tim Fairclough, Rebecca J Yiangou, Andreas Westgate, Connar Singhal, Rishi Krishnan, Anita Rick, Caroline Ives, Natalie Tomlinson, Jeremy W Alimajstorovic, Zerin Arlt, Wiebke Ottridge, Ryan S Woolley, Rebecca Shah, Pushkar Taylor, Angela E Jenkinson, Carl Lavery, Gareth G Mitchell, James |
| AuthorAffiliation | 5 Birmingham Clinical Trials Unit, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT, UK 3 Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital , Birmingham B15 2WB, UK 1 Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT, UK 12 Medical School, University of Leeds , Leeds LS2 9JT, UK 9 Nottingham Clinical Trials Unit, Queens Medical Centre , Nottingham NG7 2UH, UK 10 Emerging Innovations Unit, Discovery Sciences , BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0SL, UK 7 Department of Neurology, The Walton Centre NHS Foundation Trust , Liverpool L9 7LJ, UK 13 Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), NIHR Oxford Biomedical Research Centre, University of Oxford , Churchill Hospital, Headington, Oxford OX3 7LJ, UK 11 Upper GI Unit and Minimally Invasive Unit, Heartland |
| AuthorAffiliation_xml | – name: 8 Institute of Neurological Sciences, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde , Glasgow G51 4TF, UK – name: 3 Department of Neurology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital , Birmingham B15 2WB, UK – name: 6 Birmingham Neuro-Ophthalmology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital , Birmingham B15 2WB, UK – name: 12 Medical School, University of Leeds , Leeds LS2 9JT, UK – name: 5 Birmingham Clinical Trials Unit, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT, UK – name: 2 Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners , Birmingham B15 2TH, UK – name: 4 Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT, UK – name: 7 Department of Neurology, The Walton Centre NHS Foundation Trust , Liverpool L9 7LJ, UK – name: 11 Upper GI Unit and Minimally Invasive Unit, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust , Birmingham B9 5SS, UK – name: 10 Emerging Innovations Unit, Discovery Sciences , BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0SL, UK – name: 13 Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), NIHR Oxford Biomedical Research Centre, University of Oxford , Churchill Hospital, Headington, Oxford OX3 7LJ, UK – name: 1 Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham , Birmingham B15 2TT, UK – name: 9 Nottingham Clinical Trials Unit, Queens Medical Centre , Nottingham NG7 2UH, UK |
| Author_xml | – sequence: 1 givenname: Keira surname: Markey fullname: Markey, Keira organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 2 givenname: James surname: Mitchell fullname: Mitchell, James organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 3 givenname: Hannah surname: Botfield fullname: Botfield, Hannah organization: Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 4 givenname: Ryan S surname: Ottridge fullname: Ottridge, Ryan S organization: Birmingham Clinical Trials Unit, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 5 givenname: Tim surname: Matthews fullname: Matthews, Tim organization: Birmingham Neuro-Ophthalmology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham B15 2WB, UK – sequence: 6 givenname: Anita surname: Krishnan fullname: Krishnan, Anita organization: Department of Neurology, The Walton Centre NHS Foundation Trust, Liverpool L9 7LJ, UK – sequence: 7 givenname: Rebecca surname: Woolley fullname: Woolley, Rebecca organization: Birmingham Clinical Trials Unit, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 8 givenname: Connar surname: Westgate fullname: Westgate, Connar organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 9 givenname: Andreas surname: Yiangou fullname: Yiangou, Andreas organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 10 givenname: Zerin surname: Alimajstorovic fullname: Alimajstorovic, Zerin organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 11 givenname: Pushkar surname: Shah fullname: Shah, Pushkar organization: Institute of Neurological Sciences, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow G51 4TF, UK – sequence: 12 givenname: Caroline surname: Rick fullname: Rick, Caroline organization: Nottingham Clinical Trials Unit, Queens Medical Centre, Nottingham NG7 2UH, UK – sequence: 13 givenname: Natalie surname: Ives fullname: Ives, Natalie organization: Birmingham Clinical Trials Unit, Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 14 givenname: Angela E surname: Taylor fullname: Taylor, Angela E organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 15 givenname: Lorna C surname: Gilligan fullname: Gilligan, Lorna C organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 16 givenname: Carl surname: Jenkinson fullname: Jenkinson, Carl organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 17 givenname: Wiebke surname: Arlt fullname: Arlt, Wiebke organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 18 givenname: William surname: Scotton fullname: Scotton, William organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 19 givenname: Rebecca J surname: Fairclough fullname: Fairclough, Rebecca J organization: Emerging Innovations Unit, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0SL, UK – sequence: 20 givenname: Rishi surname: Singhal fullname: Singhal, Rishi organization: Upper GI Unit and Minimally Invasive Unit, Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham B9 5SS, UK – sequence: 21 givenname: Paul M surname: Stewart fullname: Stewart, Paul M organization: Medical School, University of Leeds, Leeds LS2 9JT, UK – sequence: 22 givenname: Jeremy W surname: Tomlinson fullname: Tomlinson, Jeremy W organization: Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, UK – sequence: 23 givenname: Gareth G surname: Lavery fullname: Lavery, Gareth G organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 24 givenname: Susan P surname: Mollan fullname: Mollan, Susan P organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK – sequence: 25 givenname: Alexandra J orcidid: 0000-0001-9396-7330 surname: Sinclair fullname: Sinclair, Alexandra J email: a.b.sinclair@bham.ac.uk organization: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32954315$$D View this record in MEDLINE/PubMed |
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| Copyright | The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. 2020 The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. |
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| Keywords | phase II 11β-hydroxysteroid dehydrogenase type 1 idiopathic intracranial hypertension papilloedema randomized controlled trial |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Keira Markey, James Mitchell and Hannah Botfield contributed equally to this work. |
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Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in... Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating... |
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| Title | 11β-Hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial |
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