scholarly journals Safety and Preliminary Efficacy of Lorcaserin for Cocaine Use Disorder: A Phase I Randomized Clinical Trial

2021 ◽  
Vol 12 ◽  
Author(s):  
Sade E. Johns ◽  
Lori Keyser-Marcus ◽  
Antonio Abbate ◽  
Edward Boone ◽  
Benjamin Van Tassell ◽  
...  

Background and Objectives: Preclinical studies show serotonin (5-HT) 5-HT2C receptor (5-HT2CR) agonists reduce cocaine-seeking and cocaine intake. This study examined safety of the 5-HT2CR agonist lorcaserin administered with cocaine in participants with cocaine use disorder (CocUD). Secondarily, subjective response to cocaine and choice of cocaine vs. money were examined.Methods: A double-blind, randomized, placebo-controlled trial of 25 inpatient non-treatment seeking participants with CocUD. Participants were randomized to either lorcaserin (n = 17) or placebo (n = 8). Primary outcome measures included cardiovascular measures and plasma cocaine levels. Secondary measures of subjective response to cocaine were assessed using a visual analog scale (VAS) and cocaine vs. money progressive ratio choice sessions.Results: Thirteen randomized participants were included in the final analysis. No serious or unexpected adverse events were related to lorcaserin. There were no significant interactions between cocaine and lorcaserin on cardiovascular measures, plasma cocaine, or subjective ratings. After multiple comparisons correction, cocaine significantly increased blood pressure, heart rate, and QTc. Lorcaserin significantly decreased VAS ratings of “feel irritable,” “feel hungry,” and “I am craving.” For the cocaine vs. money choice procedure, there was a significant interaction between choice (cocaine vs. money) and lorcaserin. Participants treated with lorcaserin were more likely to choose cocaine.Discussion and Conclusions: This study showed safety of lorcaserin administered with cocaine but lack of efficacy to reduce the reinforcing effects of cocaine.Scientific Significance: This study is the first to show a disconnect between effects of 5-HT2CR agonists on craving and cocaine choice in human cocaine users.

Author(s):  
Vijay Kumar ◽  
Avinash A. Ganapule ◽  
Sushmita Supriya ◽  
Divendu Bhushan ◽  
Pallavi Lohani ◽  
...  

Background: Objective of the study was to determine the efficacy of montelukast in reducing the severity of COVID-19 symptoms using a double blinded randomized controlled trial.Methods: Parallel, double-blinded randomized controlled trial (RCT) with placebo as comparison to montelukast. All patients above the age of 14 years both males and females, admitted with a diagnosis of mild or moderate COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period from 01 September 2020-31 January 2021) and excluding those having adverse reaction to montelukast or those not willing to participate, and pregnant and lactating females. Patients in the intervention arm were given tablet montelukast 10 mg OD HS from the day of admission for 10 days. The patients in the placebo group were given an identical appearing placebo at bedtime for 10 days from the day of admission. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with minor adjustments as per the treating team’s judgement. Primary outcome was progression of the disease to severe grade and secondary outcomes were discharge on or before day 10 from admission, admission to ICU, need for mechanical ventilation and in-hospital mortality.Results: A total of 94 patients were enrolled for the study. 90 patients, 45 in each arm were included in the final analysis. The baseline characteristics of the two arms including age, sex, comorbidities, severity at admission and treatment given apart from montelukast or placebo, were comparable with respect to these variables. This study did not find any improvement in primary outcome of progression to severe disease and secondary outcomes of intensive care unit (ICU) admission, mortality or need of mechanical ventilation, discharge on or by day 10 with the use of montelukast as compared to placebo in mild to moderate cases of COVID-19.Conclusions: There was no difference in primary or secondary outcomes with the use of Montelukast compared to placebo.


2021 ◽  
pp. svn-2021-000942
Author(s):  
Jingyi Liu ◽  
Ximing Nie ◽  
Hongqiu Gu ◽  
Qi Zhou ◽  
Haixin Sun ◽  
...  

BackgroundStudies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.MethodsWe did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.ResultsOf the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.ConclusionsAmong patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.


2009 ◽  
Vol 36 (9) ◽  
pp. 1991-1999 ◽  
Author(s):  
ROY D. ALTMAN ◽  
RENÉE-LILIANE DREISER ◽  
CHESTER L. FISHER ◽  
WALTER F. CHASE ◽  
DONATUS S. DREHER ◽  
...  

Objective.To measure the efficacy and safety of diclofenac sodium gel in patients with primary hand osteoarthritis (OA).Methods.In a randomized, double-blind, placebo-controlled trial, men and women aged ≥ 40 years diagnosed with primary OA in the dominant hand were randomly assigned to self-apply topical 1% diclofenac sodium gel (Voltaren® Gel) (n = 198) or vehicle (n = 187) to both hands 4 times daily for 8 weeks. Primary outcome measures included OA pain intensity (100-mm visual analog scale), total Australian/Canadian Osteoarthritis Hand Index (AUSCAN) score, and global rating of disease activity at 4 and 6 weeks. Secondary outcomes included onset of efficacy in Weeks 1 and 2, durability of efficacy at 8 weeks, measures of disease activity in the dominant hand, pain intensity in the non-dominant hand, AUSCAN subindices, end of study rating of efficacy, and Osteoarthritis Research Society International response criteria.Results.Diclofenac sodium gel decreased pain intensity scores by 42%–45%, total AUSCAN scores by 35%–40%, and global rating of disease by 36%–40%. Significant differences favoring diclofenac sodium gel over vehicle were observed at Week 4 for pain intensity and AUSCAN, with a trend for global rating of disease activity. At Week 6, diclofenac sodium gel treatment significantly improved each primary outcome measure compared with vehicle. Secondary outcomes generally supported the primary outcomes. The most common treatment-related adverse event (AE) was application-site paresthesia. Most AE were mild. No cardiac events, gastrointestinal bleeding, or ulcers were reported.Conclusion.Topical diclofenac sodium gel was generally well tolerated and effective in primary hand OA. (NCT ID: NCT00171665)


Perfusion ◽  
2017 ◽  
Vol 32 (7) ◽  
pp. 591-597 ◽  
Author(s):  
Geoff G. Lockwood ◽  
Leilani Cabreros ◽  
Dorota Banach ◽  
Prakash P. Punjabi

Background: Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Method: Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg-1.hr-1) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. Results: There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l-1. There were no adverse events as a consequence of the study. Conclusion: Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. Clinical trial registration: ISRCTN13424423 ( https://www.isrctn.com )


2021 ◽  
pp. 2100752
Author(s):  
Pradeesh Sivapalan ◽  
Charlotte Suppli Ulrik ◽  
Therese Sophie Lapperre ◽  
Rasmus Dahlin Bojesen ◽  
Josefin Eklöf ◽  
...  

BackgroundCombining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for COVID-19.MethodsPlacebo-controlled double-blind randomised multicentre trial. Patients ≥18 years, admitted to hospital for≤48 h (not intensive care) with a positive SARS-CoV-2 RT-PCR test, were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (DAOH14).ResultsAfter randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on February 1, 2021. A total of 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median of 9.0 DAOH14 (IQR, 3–11) versus. 9.0 DAOH14 (IQR, 7–10) in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for 1 patient in the intervention group versus. 2 patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for 9 patients in the intervention group versus. 6 patients receiving placebo (p=0.57).ConclusionsThe combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.


2020 ◽  
Vol 151 (1) ◽  
pp. 65-72
Author(s):  
David Schnadower ◽  
Robert E Sapien ◽  
T Charles Casper ◽  
Cheryl Vance ◽  
Phillip I Tarr ◽  
...  

ABSTRACT Background Gastroenteritis is a common and impactful disease in childhood. Probiotics are often used to treat acute gastroenteritis (AGE); however, in a large multicenter randomized controlled trial (RCT) in 971 children, Lactobacillus rhamnosus GG (LGG) was no better than placebo in improving patient outcomes. Objectives We sought to determine whether the effect of LGG is associated with age, weight z score and weight percentile adjusted for age and sex, or dose per kilogram administered. Methods This was a preplanned secondary analysis of a multicenter double-blind RCT of LGG 1 × 1010 CFU twice daily for 5 d or placebo in children 3–48 mo of age with AGE. Our primary outcome was moderate to severe gastroenteritis. Secondary outcomes included diarrhea and vomiting frequency and duration, chronic diarrhea, and side effects. We used multivariable linear and nonlinear models testing for interaction effects to assess outcomes by age, weight z score and weight percentile adjusted for age and sex, and dose per kilogram of LGG received. Results A total of 813 children (84%) were included in the analysis; 413 received placebo and 400 LGG. Baseline characteristics were similar between treatment groups. There were no differential interaction effects across ranges of age (P-interaction = 0.32), adjusted weight z score (P-interaction = 0.43), adjusted weight percentile (P-interaction = 0.45), or dose per kilogram of LGG received (P-interaction = 0.28) for the primary outcome. Whereas we found a statistical association favoring placebo at the extremes of adjusted weight z scores for the number of vomiting episodes (P-interaction = 0.02) and vomiting duration (P-interaction = 0.0475), there were no statistically significant differences in other secondary outcome measures (all P-interactions > 0.05). Conclusions LGG does not improve outcomes in children with AGE regardless of the age, adjusted weight z score, and adjusted weight percentile of participants, or the probiotic dose per kilogram received. These results further strengthen the conclusions of low risk of bias clinical trials which demonstrate that LGG provides no clinical benefit in children with AGE. This trial was registered at clinicaltrials.gov as NCT01773967.


Cephalalgia ◽  
2015 ◽  
Vol 36 (2) ◽  
pp. 179-184 ◽  
Author(s):  
Faruk Gungor ◽  
Kamil Can Akyol ◽  
Mustafa Kesapli ◽  
Ahmet Celik ◽  
Adeviye Karaca ◽  
...  

Objective Migraine is a leading headache etiology that frequently presents to the emergency department (ED). In the present study, we aimed to determine the efficacy of dexketoprofen in aborting migraine headaches in the ED. Methods This prospective, randomized, double-blind study was conducted in an ED of a tertiary care hospital using allocation concealment. Patients were allocated into two arms to receive the study drug; 50 mg dexketoprofen in 50 ml saline and 50 ml saline as placebo. Change in pain intensity was measured by the visual analog scale at baseline, both at 30 and 45 minutes after the study medication was administered. Rescue medication requirement and pain relapse were also recorded by a telephone follow-up at 48 hours. Results A total of 224 patients (112 in each group) were included into the final analysis. Mean age of the study participants was 37 ± 11 (SD) and 25% ( n = 56) of them were male. The median pain improvement at 45 minutes for patients receiving dexketoprofen was 55 (IQR: 49 to 60) and 30 (IQR: 25 to 35) for those receiving placebo. The mean difference between the two groups at 45 minutes was 21.4 (95% CI: 14.4. to 28.5). Rescue drugs were needed in 22.3% of patients who received dexketoprofen compared to 55.4% in patients who received placebo (dif: 33.1%; 95% CI: 20% to 45%). There were no adverse events reported in either group during the study period. Conclusion Intravenous dexketoprofen is superior to placebo in relieving migraine headaches in the ED. It may be a suitable therapy with minimum side effects in patients presenting with a migraine headache to the ED.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4104-4104 ◽  
Author(s):  
John P. Neoptolemos ◽  
Daniel Palmer ◽  
William Greenhalf ◽  
Paula Ghaneh ◽  
Richard Jackson ◽  
...  

4104 Background: We investigated the potential of biomarkers to predict efficacy of vandetanib and gemcitabine in patients with locally advanced (N = 41) or metastatic (N = 101) pancreatic cancer in a phase II double-blind multicentre randomised placebo-controlled trial. Methods: All patients were 18y or above, (ECOG = 0-2), with at least 3 mths life expectancy had gemcitabine (1000mg/m2 30min iv wkly for 7 wks, followed by a 1wk break, then cycles of wkly treatment for 3wks with a 1-wk break) and randomly assigned to 300mg/d vandetanib or placebo once daily until disease progression. The primary outcome was overall survival (OS) by intention to treat. A panel of potential biomarkers was tested to predict best survival with vandetanib and gemcitabine. Results: 142 patients were randomised, median FU = 24·9 mths with 131 deaths. The median (95% CI) OS in the 70 gemcitabine-placebo patients was 8·95 (6·55-11·7) mths and 8·83 (7·11-11·6) mths in the 72 gemcitabine-vandetanib patients (HR = 1·21, 95% CI = 0·85, 1·73; log rank X21df = 1·1; P = 0·303). A CTCAE V.4.02 rash grade 2 or above occurred in 4 (6 %) of 70 placebo patients versus 14 (19%) of 72 vandetanib patients. The median OS for the 14 vandetanib patients and with rash was 11·92 (10·89 – NA) mths, 7·76 (4·34 – 11·5) mths for the 58 vandetanib patients and without rash and 8·95 (6·55 – 11·7) mths for the gemcitabine-placebo patients (log rank Χ2 2df = 7·23; P = 0·03). We identified two biomarkers that could select patients for response to vandetanib (JN101, JN102). The biomarker combination was present in 26 patients with median OS of 12.1 (10.9, 16.0) mths versus 8.15 (6.67, 11.7) mths for 23 patients with the same biomarker profile in the placebo group (HR = 0.53 [0.29, 0.97], p = 0.0396). A logistic regression model showed that patients with JN102 were more likely to develop a rash (OR =0.81 [0.713, 0.925] p = 0.002). Conclusions: A two biomarker combination and a rash grade 2 or above may predict response to vandetanib and gemcitabine. This requires prospective evaluation. Clinical trial information: 96397434.


2007 ◽  
Vol 7 (5) ◽  
pp. 133-135 ◽  
Author(s):  
John W. Miller ◽  
Raimondo D'Ambrosio

Magnesium Sulfate for Neuroprotection After Traumatic Brain Injury: A Randomised Controlled Trial. Temkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J, Lucas T, Newell DW, Mansfield PN, Machamer JE, Barber J, Dikmen SS. Lancet Neurol 2007;6(1):29–38. BACKGROUND: Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients. METHODS: In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1 0–1·85 mmol/L or 1·25–2·5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with Clinicaltrials.gov, number NCT00004730. FINDINGS: Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean = 55 average percentile ranking on magnesium vs. 52 on placebo, 95% CI for difference – 7 to 14; p = 0·70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs. 54, 95% CI −10·5 to −2; p = 0007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect. INTERPRETATION: Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury.


1998 ◽  
Vol 172 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Franklin R. Schneier ◽  
Deborah Goetz ◽  
Raphael Campeas ◽  
Randall Marshall ◽  
Brian Fallon ◽  
...  

BackgroundMoclobemide, a reversible inhibitor of monoamine oxidase A, previously has been reported to have efficacy in the treatment of social phobia.MethodSeventy-seven non-responders to one week of single-blind placebo were randomly assigned to moclobemide or placebo for eight weeks of double-blind treatment. Outcome was assessed by independent evaluator, treating psychiatrist and self-ratings. After eight weeks, patients who were at least minimally improved continued treatment for a further eight weeks.ResultsIntention-to-treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.ConclusionsMoclobemide may have efficacy in the treatment of social phobia, but absence of significant differences on most primary outcome measures and small effect sizes for all outcome measures suggest that the magnitude of its clinical effect is small.


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