2 IIH Pressure – a randomised, controlled, double blind physiology study of the effect of Exenatide on intracranial pressure

2021 ◽  
Vol 167 (3) ◽  
pp. e1.2-e1
Author(s):  
James Mitchell ◽  
Jessica Walker ◽  
Hannah Lyons ◽  
Kristian Brock ◽  
Vivek Vijay ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Biological Effect ◽  
Human Study ◽  
Double Blind ◽  
Clinical Models ◽  
Early Phase Trial ◽  
Glucagon Like Peptide 1 ◽  
Randomised Controlled ◽  
To Receive

IntroductionRaised intracranial pressure (ICP) causes significant morbidity and mortality in a range of conditions including idiopathic intracranial hypertension (IIH) and traumatic brain injury (TBI). Exenatide is a GLP-1 receptor agonist; pre-clinical data demonstrates its ability to reduce ICP. GLP-1R agonists have also been shown to have neuro-protective properties in pre-clinical models of TBI. The objectives of this study are to assess the biological effect of a Glucagon-like Peptide 1 (GLP-1) agonist on ICP in a cohort of participants with IIH, a raised ICP model.MethodsRandomised, placebo controlled, double-blind physiology study of Exenatide in women with active IIH (>25 cmCSF lumbar puncture opening pressure and papilloedema). Telemetric, intraparenchymal ICP monitors were implanted to enable gold standard, long-term ICP monitoring (Raumedic p-Tel, Helmbrechts, Germany). Participants were randomised 1:1 to receive Exenatide (10 mcg BD sub-cutaneous) or placebo for 12 weeks. ICP was recorded over a 24-hour baseline visit, at two weeks and 12 weeks. Monthly headache diaries were completed at baseline and 8–12 weeks. Significance was set at p<0.1 as an early phase trial.ResultsOf the 16 participants recruited, 15 were randomised and completed the study: age 29.5 ±9.5 years, BMI 38.1 ±6.2 kg/m2, ICP 30.6±5.1 cmCSF. All ICP monitor implants were well tolerated and allowed successful ICP quantification. A significant reduction in ICP was noted at all timepoints: at 2.5 hours -5.7 cm CSF (p=0.031), at 24 hours -6.3 cmCSF (p=0.095), and at 12 weeks -5.6 cmCSF (p=0.064).ConclusionsWe report the first human study to assess the biological effect of the GLP-1 agonist Exenatide on ICP in IIH utilising highly accurate implantable telemetric ICP monitors. Exenatide reduced ICP at all timepoints including acutely at 2.5 hrs and during chronic dosing. New therapies for ICP modulation are a significant un-met need in both military and civilian spheres.

Childhood Absence Epilepsy - A Review of Treatment Strategies and Perspectives for the Future

2012 ◽  
Vol 7 (1) ◽  
pp. 62
Author(s):  
Sylvain Rheims ◽  
Philippe Ryvlin ◽  
◽  
Keyword(s):  
Sodium Valproate ◽  
Controlled Trial ◽  
Treatment Strategies ◽  
Absence Epilepsy ◽  
Childhood Absence Epilepsy ◽  
Double Blind ◽  
Therapeutic Decisions ◽  
Randomised Controlled ◽  
Outcomes Management

Childhood absence epilepsy (CAE) is one of the most common forms of paediatric epilepsy. However, there is still a gap between the prevalence of CAE in paediatric epilepsies and the paucity of available data regarding its therapeutic management. Only nine randomised controlled trials have been published in the field over the past four decades, with many suffering from major methodological limitations. A recent large randomised double-blind controlled trial reported that ethosuximide and sodium valproate are the most effective anti-epileptic dugs in CAE and that cognitive performance appears to be better with ethosuximide than with sodium valproate. Although lamotrigine also demonstrated anti-absence properties in the same trial, it proved to be significantly less efficacious than ethosuximide or sodium valproate. Despite these recent advances, several questions, including long-term outcomes, management of refractory CAE and treatment duration, remain unanswered and further studies are required to refine therapeutic decisions.

New treatments for panic

1998 ◽  
Vol 13 (S2) ◽  
pp. 75s-81s ◽  
Author(s):  
JC Ballenger
Keyword(s):  
Panic Disorder ◽  
Adverse Events ◽  
Dropout Rate ◽  
Prolonged Treatment ◽  
Double Blind Study ◽  
Onset Of Action ◽  
Double Blind ◽  
New Treatments ◽  
To Receive

SummaryPanic disorder is a chronic condition for many patients and can be socially, emotionally and occupationally disabling. Until recently, clomipramine and alprazolam were the only drugs approved for its treatment. While widely used in the US and Europe, both belong to drug classes (tricyclics and benzodiazepines) with well-recognised side effects that can be problematic and thus limit their use. Recently, paroxetine became the first selective serotonin reuptake inhibitor to receive approval and licensing for panic disorder.The short- and long-term efficacy and tolerability of paroxetine in panic disorder has been established in clinical trials of almost 1,000 patients meeting Diagnostic and Statistical Manual (DSM)-IIIR criteria for panic disorder, with or without agoraphobia. In a 12-week double-blind study of 120 panic patients receiving standardised cognitive therapy, paroxetine was significantly more effective than placebo in reducing panic attack frequency. In a 12-week placebo-controlled comparison in 367 panic patients, paroxetine was at least as effective as clomipramine and better tolerated. There was also some evidence that paroxetine had an earlier onset of action than clomipramine.A 9-month extension of the placebo-controlled comparison with clomipramine showed that the efficacy of paroxetine and clomipramine is maintained when treatment is continued into the longer term. In a relapse prevention study, 105 responders to 3 months' treatment with paroxetine or placebo were re-randomised, either to continue existing treatment or to receive placebo for 3 months. Only 5% of patients who continued to take paroxetine experienced a relapse compared with 30% of those who switched to placebo (P = 0.002). Paroxetine was generally well tolerated. In the short-term trials, the frequency of withdrawals due to adverse events (7.3%) was lower than that for placebo (11.4%) or clomipramine (14.9%). In the longer term, the dropout rate due to adverse events increased in the clomipramine group (19.0%) but was unchanged in the paroxetine group (7.4%). Since most patients with panic disorder will require prolonged treatment, the long-term tolerability of paroxetine and its lack of potential for dependence are important advantages that will encourage good compliance with treatment and improve the quality of life of patients.

scholarly journals Effect of Dehydroepiandrosterone Replacement on Lipoprotein Profile in Hypoadrenal Women

2009 ◽  
Vol 94 (3) ◽  
pp. 761-764 ◽  
Author(s):  
Manivannan Srinivasan ◽  
Brian A. Irving ◽  
Ketan Dhatariya ◽  
Katherine A. Klaus ◽  
Stacy J. Hartman ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Profile ◽  
Double Blind ◽  
Caucasian Women ◽  
Study Participants ◽  
The Impact ◽  
To Receive

Abstract Context: Levels of dehydroepiandrosterone (DHEA) and its sulfate form (DHEAS) are inversely associated with cardiovascular mortality in men but not women. Very little evidence is available on the impact of DHEA administration on lipoprotein profile in women. DHEAS levels are very low/undetectable in hypoadrenal women. Objective: The objective of the study was to determine the impact of DHEA replacement on lipoprotein profile in hypoadrenal women. Design and Setting: A double-blind, randomized, placebo-controlled, cross-over design study was conducted at the Mayo Clinic. Participants: Thirty-three hypoadrenal Caucasian women (mean ± sd; age 50.3 ± 15.2 yr, body mass index 26.6 ± 4.4 kg/m2) took part in the study. Intervention: Study participants were assigned to receive either a placebo or 50 mg/d of DHEA for 3 months each. Lipid levels and lipoprotein profile were analyzed using the Lipo Science Lipoprotein nuclear magnetic resonance system. Main Outcome Measures: Changes in various lipoprotein sizes and levels were measured. Results: The DHEA period had higher plasma DHEAS levels than during placebo (&lt;0.3 ± 0.0 vs. 3.5 ± 1.3 nmol/liter, P &lt; 0.001). DHEA replacement significantly reduced total cholesterol (20.0 vs. −22, P = 0.02) and high-density lipoprotein (HDL) levels (2.0 vs. −6.0, P = 0.006) and tends to reduce triglyceride and total low-density lipoprotein levels. Although, DHEA replacement had no effect on low-density lipoprotein particle size, it significantly reduced larger HDL particles and to modest extent small HDL particles. Conclusions: Our study findings showed that oral DHEA administration in hypoadrenal women results in an unfavorable lipoprotein profile. The results warrant long-term studies to determine the impact of DHEA replacement on cardiovascular risk.

scholarly journals Effectiveness of a Fortified Drink in Improving B Vitamin Biomarkers in Older Adults: A Controlled Intervention Trial

2021 ◽  
Author(s):  
Maria Heffernan ◽  
Leanne C Doherty ◽  
Roberta Hack Mendes ◽  
Michelle Clarke ◽  
Stephanie Hodge ◽  
...  
Keyword(s):  
Older Adults ◽  
Controlled Trial ◽  
Intervention Strategy ◽  
B Vitamins ◽  
Double Blind ◽  
Intention To Treat ◽  
Vitamin Status ◽  
Randomised Controlled ◽  
B Vitamin ◽  
To Receive

Abstract BackgroundOlder adults are reported to have sub-optimal B vitamin status; targeted food-based solutions may help to address this. The objectives of the OptiAge food intervention study were to develop and investigate the effectiveness of a B vitamin-fortified drink in improving B vitamin biomarkers in older Irish adults with a primary outcome of change in B vitamin biomarker concentrations.MethodsA multicentre double-blind randomised controlled trial was performed in University College Dublin and Ulster University. Participants aged > 50 years were recruited following screening for exclusion criteria i.e. taking medications known to interfere with B vitamin metabolism, supplements containing B vitamins, consuming >4 portions of B-vitamin fortified foods per week or diagnosed with gastrointestinal, liver or pulmonary disease. Recruited participants were randomised with gender and centre as factors in the randomisation to receive either B vitamin-fortified or placebo drinks (developed by Smartfish, Norway) daily for 16 weeks.ResultsA total of 95 participants were randomised, of which 81 commenced the trial. Of these, 70 completed - 37 in the active and 33 in the placebo groups. Intention to treat (ITT) analysis of the B vitamins demonstrated a significant improvement in all B vitamins biomarkers in the active compared to placebo groups (p<0.01 for Folate, Vitamin B12, Vitamin B6, and Riboflavin). A significant lowering of plasma homocysteine from 11.9 (10.3-15.1) µmol/L to 10.6 (9.4-13.0) µmol/L (functional marker of B vitamin status) was also observed in response to the active treatment (P<0.001). Similar results were seen in a per-protocol analysis.ConclusionsThe results demonstrate that a B vitamin-fortified drink was effective in optimising B vitamin status, making this a useful intervention strategy to improve B vitamin status in older adults. Trial registration: ISRCTN, ISRCTN61709781. - Retrospectively registered, https://www.isrctn.com/ISRCTN61709781

scholarly journals Effect of multifibre mixture with prebiotic components on bifidobacteria and stool pH in tube-fed children

2010 ◽  
Vol 104 (10) ◽  
pp. 1514-1522 ◽  
Author(s):  
Dominique Guimber ◽  
Béatrice Bourgois ◽  
Laurent Beghin ◽  
Sébastien Neuville ◽  
Philippe Pernes ◽  
...  
Keyword(s):  
Blood Parameters ◽  
Gut Health ◽  
Neurologically Impaired ◽  
Anthropometric Measures ◽  
Double Blind ◽  
Normal Ranges ◽  
Micronutrient Status ◽  
Bowel Movements ◽  
Randomised Controlled

The objective of the present study was to evaluate the effect of a paediatric tube feed supplemented with a multifibre mixture on the gut microbiota and nutritional and micronutrient status of children on long-term enteral nutrition (EN). A randomised, controlled, double-blind, cross-over trial (2 × 3 months) with a washout period of 1 month was carried out. Twenty-seven children (80 % neurologically impaired) aged 11·9 (sd3·9) years, on long-term EN (4·8 (sd3·9) years) were recruited. The analyses of the children's faecal pH, microbiota along with anthropometric measures, bowel movements and markers of blood micronutrient status were made. Twenty children completed the study. A significant increase in the proportion of stool bifidobacteria (+16·6 %,P < 0·05) was observed during the multifibre period than during the fibre-free period, together with a significant reduction in stool pH (P < 0·001). Stool frequency and consistency as well as growth did not differ between the two periods. There was a significant increase (P < 0·05) in plasma ferritin at the end of the fibre-free period, but plasma ferritin levels remained within normal ranges during both periods. No diet effects on other blood parameters were observed. In conclusion, addition of a multifibre mixture with prebiotic components to paediatric EN is well tolerated, promotes bifidobacteria and reduces stool pH, indicating an improved gut health.

Reporting of long-term extension studies: lack of consistency calls for consensus

2011 ◽  
Vol 70 (6) ◽  
pp. 886-890 ◽  
Author(s):  
Maya H Buch ◽  
Daniel Aletaha ◽  
Paul Emery ◽  
Josef S Smolen
Keyword(s):  
Conflicts Of Interest ◽  
Therapeutic Interventions ◽  
Ethical Considerations ◽  
Double Blind ◽  
Safety Reporting ◽  
Potential Safety ◽  
Reliable Interpretation ◽  
Randomised Controlled ◽  
Term Data

Double-blind, randomised controlled studies represent the gold-standard approach to determine the safety and efficacy of therapeutic interventions. In chronic conditions such as rheumatoid arthritis (RA), long-term data are vital to confirm maintenance of effect and identify potential safety signals. The recent introduction of numerous biological therapies for RA has been followed by various long-term extension (LTE) studies. Although useful, the design and method of analysis in such studies vary significantly, partly due to their complexity. This viewpoint highlights general considerations needed when undertaking a LTE study and illustrates the lack of consistency in studies of RA to date. It addresses issues of selection bias, patient discontinuation and missing data. Although used for safety reporting, the lack of adequate powering makes LTE studies of limited benefit. Ethical considerations and challenges are highlighted, including potential conflicts of interest. Finally, the authors suggest the need for consensus to ensure more reliable interpretation and application of data for clinical practice. Following the development of guidelines on reporting of clinical trials in RA and more recently, registry data, a similar approach for LTE studies would be a useful endeavour.

scholarly journals Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease

2020 ◽  
Author(s):  
Aaron Broadwell ◽  
Arkadi Chines ◽  
Peter R Ebeling ◽  
Edward Franek ◽  
Shuang Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mineral Density ◽  
Pivotal Phase ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Ckd Stage ◽  
Moderate Chronic Kidney Disease ◽  
To Receive

Abstract Context The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown. Objective This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (CKD) (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies. Participants and Methods Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than –2.5 to greater than –4.0 at the total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible participants could enroll in the extension to receive denosumab 60 mg subcutaneously every 6 months. Change in estimated glomerular filtration rate (eGFR) from study baseline and annualized rates of fracture and adverse events (AEs) were the main outcome measures. Results Most participants (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD stage 2 or 3 remained within the same CKD subgroup at study completion; less than 3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of participants reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) both for the long-term (54% vs 52% vs 57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b subgroup, crossover arm. Conclusion The safety and efficacy of denosumab did not differ among participants with mild to moderate CKD.

scholarly journals DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Sandhia Ponnarambil ◽  
John Downie ◽  
Karin Bowen ◽  
Åsa Hellqvist ◽  
...  
Keyword(s):  
High Dose ◽  
Treatment Cessation ◽  
Uncontrolled Asthma ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Long Term Treatment ◽  
To Receive

Abstract Background Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies. Methods DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated. Discussion DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. Trial registration NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

scholarly journals Comparison of a Chinese Herbal Medicine (CCH1) and Lactulose as First-Line Treatment of Constipation in Long-Term Care: A Randomized, Double-Blind, Double-Dummy, and Placebo-Controlled Trial

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Chien-Hsun Huang ◽  
Jui-Shan Lin ◽  
Tsai-Chung Li ◽  
Shih-Chang Lee ◽  
Hsiu Po Wang ◽  
...  
Keyword(s):  
Long Term Care ◽  
Controlled Trial ◽  
Healthcare Providers ◽  
Double Blind ◽  
Term Care ◽  
Care Facilities ◽  
Bowel Movements ◽  
Institutionalized Patients ◽  
To Receive

Many institutionalized patients and their healthcare providers are dissatisfied with current laxative therapy. This study compared therapeutic efficacy, safety, and laxative cost of an herbal formula (CCH1) and lactulose for long stay patients with constipation. In this double-blind, double-dummy, and placebo-controlled trial, we randomized 93 residents with chronic constipation from two long-term care facilities in Taiwan to receive either CCH1 with lactulose placebo or CCH1 placebo with lactulose for 8 weeks, then followed up for 4 weeks without study medication. Both treatments were effective and well tolerated for patients, but CCH1 produced more spontaneous bowel movements, less rectal treatments, less amount of rescue laxative, and lower laxative cost than lactulose during treatment. No significant differences were found in stool consistency, stool amount, global assessment, and safety concerns. In conclusion, our results suggest that CCH1 may have better efficacy and could be used as an alternative option to lactulose in the treatment of constipation in long-term care.

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