Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate.
Ontology highlight
ABSTRACT:
SUBMITTER: Kluge M
PROVIDER: S-EPMC3598541 | biostudies-literature | 2013 Feb
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:IntroductionSepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome.Methods and analysisImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation.Ethics and disseminationThe protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d'éthique de la recherche sur l'être human of Switzerland. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04990232.
| S-EPMC9772655 | biostudies-literature
Project description:ObjectiveTo evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy.MethodsThis was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere.ResultsThirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect.ConclusionsThis single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required.Clinicaltrialsgov identifierNCT02178995.Classification of evidenceThis study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints.
| S-EPMC5278946 | biostudies-literature
Project description:Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of about 1/3000, independent of ethnicity, race, or gender. Attention Deficit Hyperactivity like Disorder (ADHD)-like characteristics are often reported in patients with NF1. We hypothesised that learning disabilities in NF1 children were related to ADHD symptoms. Treatment with methylphenidate (MPD) has improved learning disabilities in ADHD by acting on neurotransmitters. Our objective was to evaluate its efficacy on ADHD-like symptoms in neurofibromatosis type 1 children (7-12 years).This was a randomised, double blind, placebo controlled, and crossover trial comparing 0.5 to 0.8 mg/kg/d of MPD as it is indicated for ADHD to placebo in NF1 children with ADHD-like symptoms. Children aged 7 to 12 years were eligible when their IQ was between 80 and 120. The total follow-up was 9 weeks including 4 weeks for each period and 1 week wash out. Fifty subjects (25 for each period) were required for testing the primary study hypothesis. The main outcome was an improvement in scores on the simplified Conners' Parent Rating Scale.Thirty-nine patients were included between April 2004 and December 2010. Twenty participants received MPD and 19 placebo during the first period. They all completed the trial. MPD decreased the simplified Conners by 3.9 points (±1.1, p?=?0. 0003).This is the first randomised controlled trial showing the short-term benefit of MPD on simplified Conners scores in NF1 children.ClinicalTrials.gov NCT00169611.
| S-EPMC4172829 | biostudies-literature
Project description:Hyperprolactinaemia is a troublesome side-effect of treatment with antipsychotics.This double-blind, placebo-controlled study aimed at examining the effect of adjunctive treatment with 10?mg aripiprazole on prolactin levels and sexual side-effects in patients with schizophrenia symptomatically maintained on risperidone.Thirty patients taking risperidone were enrolled into the trial (CTRI/2012/11/003114). Aripiprazole was administered at a fixed daily dose of 10?mg/day for 8 weeks. Serum prolactin was measured at baseline and at 8 weeks. Hyperprolactinaemia-related problems, psychopathology and side-effects were evaluated every 2 weeks.Prolactin levels decreased by 58% in the aripiprazole group compared with an increase by 22% in the placebo group. Prolactin levels normalised in 46% of patients in the aripiprazole group (number needed to treat, NNT=2). Aripiprazole improved erectile dysfunction in five out of six patients. There were no significant differences in change in psychopathology or side-effects between groups.Adjunctive aripiprazole reduced prolactin levels in those treated with risperidone, with no effect on psychopathology and extrapyramidal symptoms. This is a potential treatment for hyperprolactinaemia observed during treatment with second-generation antipsychotics.None.© The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
| S-EPMC4998932 | biostudies-other
Project description:BackgroundMethylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue.MethodsIn this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed.FindingsBetween Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0-53·6) at baseline, 40·6 (38·2-43·1) with placebo, 41·3 (38·8-43·7) with amantadine, 39·0 (36·6-41·4) with modafinil, and 38·6 (36·2-41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil).InterpretationAmantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis.FundingPatient-Centered Outcomes Research Institute.
| S-EPMC7772747 | biostudies-literature
Project description:OBJECTIVE:To determine the effectiveness of methylphenidate for depression treatment in patients with advanced cancer. DESIGN:An 18-day randomized, double-blind, placebo-controlled clinical trial of methylphenidate for treatment of depression in selective serotonin reuptake inhibitor-treated patients with advanced cancer in hospice or receiving palliative care. The primary outcome was depression remission, defined as a ?50% reduction in score on the Montgomery-Asberg Depression Rating Scale. RESULTS:Among 47 enrolled participants, 34 were randomized. At study day 18, 85% of the methylphenidate and 60% of the placebo group were in depression remission (P = .22). Mean time to depression remission was 10.3 days [standard error (SE) 1.8] in the methylphenidate and 8.1 (SE 1.3) in the placebo group (P = .48). The mean baseline score for the Hospital Anxiety and Depression Scale (HADS) was 10.4 in each group and decreased by 3.6 (SE 1.1) in the methylphenidate and 2.3 (SE 1.2) in the placebo group (P = .51) by day 18. Once in remission, 1 methylphenidate and 5 placebo participants relapsed to depression (P = .18). There was no difference in mortality between the groups during the trial. Trial results were limited by small sample size attributed to difficulties in recruiting terminally ill patients. CONCLUSIONS:This trial failed to demonstrate that methylphenidate treatment in selective serotonin reuptake inhibitor-treated patients had a significant effect on depression remission in patients with advanced cancer. This study underscores the difficulties in conducting trials for symptom management in patients with shortened life expectancy.
| S-EPMC5509522 | biostudies-other
Project description:Background: To evaluate the efficacy, safety and tolerability of methylphenidate (MPH) for cognitive function in older patients with mild cognitive impairment (MCI). Methods: Male and female subjects aged 65 years and older with a clinical diagnosis MCI were included in an exploratory randomized, double-blind, placebo-controlled trial. Eligible subjects were assigned to either treatment with immediate-release MPH or placebo. The active compound was administered in an increasing-dose stepwise fashion, namely 10 mg MPH on day 1, 20 mg on day 2, and 30 mg on day 3. Subjects remained under observation for 4 h following drug administration and were monitored for changes in blood pressure and for adverse events. Cognitive outcome measures included the Montreal Cognitive Assessment (MoCA) and the Neurotrax Mindstreams computerized cognitive assessment battery. Results: Of 17 subjects enrolled, 15 subjects completed the study, 7 in the active MPH group and 8 in the placebo group. The average age of the participants was 76.1 ± 6.6 years and 10 (66.7%) were men. Following the final dose a significant benefit on memory (predominantly non-verbal memory) was found in the MPH group. While 12 adverse events were reported, they were all rated as mild to moderate. Conclusions: Our finding of modest beneficial effects of MPH on memory tests in older subjects with MCI in this exploratory study is of interest and should be investigated in further studies.
| S-EPMC7900434 | biostudies-literature
Project description:ObjectiveThe authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients.MethodThe authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition.ResultsDaily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects.ConclusionsCombined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.
| S-EPMC4451432 | biostudies-literature
Project description:Background and Purpose: The effect of Iguratimod in the treatment of rheumatoid arthritis was confirmed in past studies. In terms of the mechanism of the effect and clinical application experience, Iguratimod has a potential value in the treatment of spondyloarthritis (SpA). This study evaluated the efficacy and safety of Iguratimod on active SpA. Methods: Subjects with active SpA were enrolled and randomly divided into two groups at a ratio of 1:2 (placebo vs. Iguratimod). On the basis of non-steroidal anti-inflammatory drugs, combined treatment with Iguratimod or placebo, followed by follow-up every 4 weeks for 24 weeks. The primary efficacy endpoint was to evaluate the alleviation rate of ASAS20; the important improvement of ASDAS and the efficacy of spinal mobility, physical function and quality of life at the 24th week. Results: A total of 48 cases in the Iguratimod group and 25 cases in the placebo group were included in the final analysis. On the 24th week, the percentage of responders to ASAS20 (80 vs. 44%) and ASAS40 (56 vs. 20%) treated with Iguratimod were significantly higher than that in the placebo group (P < 0.05). Twelve cases had gastrointestinal discomfort, of which eight were in the Iguratimod group (16.7%, one case withdrew from the study due to diarrhoea) and four were in the placebo group (16.0%). No significant difference was found between the two groups (P < 0.05). Three cases of elevated transaminase were observed in the Iguratimod group and none in the placebo group, with no significant difference (P < 0.05). Conclusion: Iguratimod could significantly reduce the symptoms and signs of patients with active SpA. It could improve the physical function and quality of life of these patients and the overall safety and tolerance are good.
| S-EPMC8208078 | biostudies-literature
Project description:BackgroundTuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex.MethodsIn this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30.FindingsBetween 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (p = 0.28). Twenty-seven patients had SEGAs: 13 received placebo and 14 metformin. The median percentage change in SEGA volume was +3.0% (IQR -22.8% to +27.7%) for the placebo group and - 20.8% (IQR - 47.1% to - 5.0%) for the metformin group (p = 0.03). Twenty-one patients were assessed for seizure frequency: 9 received placebo and 12 received metformin. In the metformin group, a mean reduction of 43.7% from baseline in seizures was observed and in the placebo group a 3.1% mean reduction was observed, with a difference in response of 40.6% (95% CI -3.1% to +84.2%, p = 0.03). There were no significant differences between metformin and placebo groups for the other secondary outcomes. There were no deaths. Three serious adverse events (SAEs) occurred during the trial (all patients on metformin).InterpretationMetformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified.FundingThis study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB).
| S-EPMC7910694 | biostudies-literature