Novel Neurological and Anti-epileptic Drug of Combined Valproic acid and Topiramate (TopVal).

2021 ◽  
Author(s):  
Mina Kelleni
Keyword(s):  
Valproic Acid ◽  
Clinical Trials ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Refractory Epilepsy ◽  
Neurological Diseases ◽  
Therapeutic Option ◽  
Anti Epileptic Drug

In this communication we demonstrate the development of a novel neurological compound of combined valproic acid and topiramate (TopVal) which might offer a potential therapeutic option for epilepsy, refractory epilepsy as well as other neurological diseases currently managed by either drug. A lower administered dose might help to achieve a higher safety profile when enrolled for randomized clinical trials against either drug.

Designing a clinical trial for neurorehabilitation

2020 ◽  
pp. 47-60
Author(s):  
Bruce Dobkin ◽  
Clarisa Martinez
Keyword(s):  
Clinical Trials ◽  
Gold Standard ◽  
Trial Design ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Neurological Diseases ◽  
Parallel Group ◽  
Study Participants ◽  
Parallel Group Trial ◽  
Group Trial

The design, implementation, and analysis of clinical trials for the types of complex therapies needed to lessen impairments and disabilities that result from neurological diseases are reviewed. A multistep progression from feasibility testing in small groups of selected participants to the demonstration of efficacy in large-scale, multicentre randomized clinical trials is presented. Designs other than the ‘gold standard’ parallel-group trial can be used to optimize the contents of a new therapeutic strategy. Emphasis is placed on defining clinical characteristics and establishing a stable functional baseline for study participants. How the choices of outcome measure and comparison intervention affect the statistical and clinical significance of trial results are highlighted. Discussion of methodological concerns about randomization and blinded outcome assessment is followed by a review of common statistical confounders in neurorehabilitation trials. The use of consensus standards about trial reporting provides a valuable checklist for basic decisions in trial design.

scholarly journals Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

2016 ◽  
Vol 34 (7) ◽  
pp. 731-739 ◽  
Author(s):  
Caroline Happold ◽  
Thierry Gorlia ◽  
Olivier Chinot ◽  
Mark R. Gilbert ◽  
L. Burt Nabors ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Clinical Trials ◽  
Radiation Therapy ◽  
Drug Use ◽  
Antiepileptic Drug ◽  
Randomized Clinical Trials ◽  
Radiation Therapy Oncology Group ◽  
Gene Promoter ◽  
Newly Diagnosed ◽  
Newly Diagnosed Glioblastoma

Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use. Conclusion The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials.

scholarly journals Existing and Emerging Approaches to Treating Chronic Inflammatory Demyelinating Polyneuropathy

US Neurology ◽  
2019 ◽  
Vol 15 (1) ◽  
pp. 33
Author(s):  
Brannagan III Thomas H ◽  
Khosro Farhad ◽  
Inna Kleyman ◽  
Megan Leitch ◽  
Rebecca Traub ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Neurological Diseases ◽  
Demyelinating Polyneuropathy ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Inflammatory Demyelinating Polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disabling disease with an incompletely understood autoimmune etiology. Differentiating the condition from other neurological diseases can be challenging and appropriate treatment is often delayed. Intravenous immunoglobulin (IVIg), plasmapheresis, corticosteroids and subcutaneous immunoglobulin (SCIg) have all been demonstrated to be beneficial in placebo-controlled, randomized clinical trials. Corticosteroids, including methylprednisolone and dexamethasone are effective and frequently used in CIDP but their long-term use is limited by side effects. One of the most commonly prescribed treatments for CIDP is IVIg which diminishes inflammatory processes and prevents disease progression. Treatment with IVIg has proven effective in randomized, double blind, placebo controlled, clinical trials and the results support its use in CIDP. For some patients, the benefit of IVIg, is limited by the frequency of infusions and systemic side effects such as flu-like symptoms, headache, and nausea. Other effective treatments for CIDP include corticosteroids that are associated with serious side effects in long-term use and plasmapheresis which requires specialized facilities. More recently, SCIg has been demonstrated in double blind, placebo-controlled studies to be effective for maintenance use in CIDP in patients whose disease has been controlled by IVIg. In a large clinical trial, 0.2 g/kg and 0.4 g/kg body weight doses of 20% SCIg equivalent to 1 mL/kg or 2 mL/kg, respectively, administered weekly, demonstrated efficacy in CIDP and were well tolerated. Immunomodulating treatments such as cyclophosphamide, mycophenolate mofetil and rituximab have also shown efficacy in select populations with CIDP.

scholarly journals Acupuncture as a therapeutic option for tension-type headache: A Systematic Review

2021 ◽  
Author(s):  
Camila Puton, Caio de Almeida Lellis ◽  
Caio Reis Borges ◽  
Giovanna Garcia de Oliveira
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Relaxation Training ◽  
Randomized Clinical Trials ◽  
Therapeutic Option ◽  
Control Process ◽  
Tension Headache ◽  
Primary Headache ◽  
Tension Type Headache ◽  
Type Headache

Introduction: Tension headache (TTS), the most common type of primary headache, is characterized by tightness pain, typically bilateral, lasting hours or days, significantly impairing daily activities. Objectives: To review the literature on the use of acupuncture in the management of TTS, evaluating its safety and efficacy. Design and setting: A systematic review conducted at the Pontifical Catholic University of Goiás. Methods: A systematic literature review was performed in the PubMed, EMBASE and Virtual Health Library databases, with the terms: “Tension-Type Headache AND Acupuncture”. Randomized studies and clinical trials published in the last 10 years were selected. Results: Two studies, one clinical trial and one randomized trial, concluded that combining acupuncture with another therapy involving movement, such as stretching, physical therapy techniques, or relaxation training, led to reduced pain intensity and improved quality of life in patients with TTS. In contrast, other randomized clinical trials concluded that relaxation training decreased the intensity, frequency of attacks, and adjunctive symptoms of headache (sleep and vitality) more than acupuncture. Finally, acupuncture was compared with the simulated control process in the prevention of TTS, but there were no statistically significant differences between the two groups evaluated. Conclusion: The literature indicated that the combination of acupuncture with other therapeutic options was safe and effective in the management and prevention of TTS. Studies with greater scientific rigor should be conducted for a better understanding of this therapeutic option.

Efficacy and Safety Profile of Celecoxib for Treating Advanced Cancers: A Meta-analysis of 11 Randomized Clinical Trials

2014 ◽  
Vol 36 (8) ◽  
pp. 1253-1263 ◽  
Author(s):  
Jian Chen ◽  
Peng Shen ◽  
Xiao-chen Zhang ◽  
Meng-dan Zhao ◽  
Xing-guo Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Efficacy And Safety

scholarly journals Efficacy and Safety Profile of Ixazomib Based Regimens in Relapsed/Refractory Multiple Myeloma: A Meta-Analysis of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ashar Ali ◽  
Anum Javaid ◽  
Muhammad Abu Zar ◽  
Atif Sohail ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Case Series ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Grade 3

Background: Multiple myeloma (MM) is an incurable disease, and clinical trials with newer agents have shown improved patient outcomes. There is a need for effective and tolerable treatment for patients with relapsed/refractory MM (RRMM). Proteasome inhibitors (bortezomib, carfilzomib, ixazomib) remain an integral part of regimens used in RRMM or newly diagnosed (ND) MM. This meta-analysis aims to assess the efficacy and safety of ixazomib (Ixa) based regimens in RRMM. Methods: A comprehensive literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used MeSH and Emtree terms, "ixazomib" AND "multiple myeloma" from the inception of literature till 06/01/2020. We screened 1529 articles and included 3 randomized clinical trials (RCT, N=907) and 8 non-randomized clinical trials (NRCT, N=321). We excluded case reports, case series, review articles, meta-analysis, observational studies, and clinical trials that didn't provide data about the efficacy and safety of Ixa in RRMM. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 11 clinical trials (N=1228), the age range of patients was 30-91 years. In Phase III RCTs (N=837) comparing Ixa + Lenalidomide (Len) + dexamethasone (Dex) vs. placebo + Len + Dex, risk ratio of overall response rate (ORR), complete response (CR), and very good partial response (VGPR) were 1.14 (95% CI=1.05-1.24, I2=80%), 1.87 (95% CI=1.17-2.99, I2=0), and 1.15 (95% CI=0.95-1.40, I2=0), respectively in favor of Ixa + Len + Dex. (Fig 1-3) Grade 3 or higher treatment-related adverse events (TRAEs) thrombocytopenia, diarrhea, and rash were reported in 20%, 5.7% and 6.4% of the patients in the Ixa group vs. 10%, 2.1%, and 2.8% in the placebo group, respectively. In a Phase II RCT by Kumar et al (N=70) comparing the Ixa dosage, 4 mg Ixa + Dex yielded an ORR of 31%, CR 2.8%, and VGPR 17.1%, while 5.5 mg Ixa yielded improved ORR of 54%, CR 2.8%, and VGPR 25.7%. In a NRCT by Costello et al. (N=6), Ixa + daratumumab (Dara) + Pom + Dex yielded 100% ORR, CR 5% (95% CI=0.17-0.83), and VGPR 50% (95% CI=0.17-0.83). ≥Grade 3 TRAEs were hypertension (16%), and hematological (33%). Among 417 patients from two RCT in single arm who received Ixa + Len + Dex, pooled ORR was 70% (95% CI=0.53-0.82, I2=84%), pooled CR 11% (95% CI=0.8-0.14, I2=0), and pooled VGPR was 29% (95% CI=0.18-0.43, I2=66%). In a NRCT by Dhakal et al. (N=19), Ixa + bendamustine + Dex yielded an ORR 58% (95% CI=0.36-0.77), CR 0, and VGPR 11% (95% CI =0.03-0.34). ≥Grade 3 TRAEs were neutropenia 31%, thrombocytopenia 52%, and diarrhea 10%. In 2 NRCT (N=106), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR 52% (95% CI=0.42-0.61, I2=0), CR 4% (95% CI=0.01-0.10, I2=0), and VGPR 17% (95% CI=0.11-0.25, I2=0). ≥Grade 3 TRAEs were thrombocytopenia (15%), and upper abdominal pain (4%). In a NRCT by Ludwig et al. (N=90), Ixa + thalidomide (Thal) + Dex yielded an ORR 51% (95% CI=0.41-0.61), CR 9% (95% CI=0.5-0.17), and VGPR 14% (95% CI=0.09-0.23). ≥Grade 3 TRAEs were anemia (17.8%), and infections (16.1%). In a NRCT by Krishnan et al. (N=31), Ixa + Pomalidomide (Pom) + Dex yielded an ORR 48% (95% CI=0.32-0.65) and VGPR 16% (95% CI=0.07-0.33). (Fig 4-6) ≥Grade 3 TRAEs were neutropenia (10%), and lymphopenia (35%). In 2 NRCT by Kumar et al. (N=70) of two drugs combination, Ixa + Dex yielded a pooled ORR 43% (95% CI=0.28-0.59, I2=47%), pooled CR 1% (95% CI=0-0.09, I2=0), and pooled VGPR 24% (95% CI=0.16-0.36, I2=0). ≥Grade 3 TRAEs were hematological (28%), and non-hematological (22.8%). In 2 NRCT of Ixa monotherapy (N=69), pooled ORR was 17% (95% CI=0.10-0.28, I2=0), and pooled CR 6% (95% CI=0.2-0.22, I2=0). (Fig 4-6) ≥Grade 3 TRAEs were anemia (11%), thrombocytopenia (5.4%), and neutropenia (2.7%). Conclusion: Our study provides useful insight into relative efficacy of various Ixa regimens for the treatment of RRMM. The pooled analysis of RCT showed that the combination of Ixa + Len + Dex yielded better response as compared to placebo. In the pooled analysis of outcomes in single arm NRCT, Ixa + Dara + Pom + Dex and Ixa + Len + Dex showed better efficacy outcomes as compared to Ixa + Dex in combination with Thal, Cyc, or Bendamustin. Three drugs Ixa combination regimens had better efficacy as compared to two drugs combination of Ixa + Dex and Ixa monotherapy. Ixa was well tolerated with acceptable safety profile. Additional multicenter, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals The Role of Niacin in Cardiovascular Disease Prevention: A Systematic Review and Meta-analysis

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
E D’Andrea ◽  
S Hey ◽  
C L Ramirez ◽  
A Kesselheim
Keyword(s):  
Systematic Review ◽  
Cardiovascular Disease ◽  
Clinical Trials ◽  
Secondary Prevention ◽  
Randomized Clinical Trials ◽  
Therapeutic Option ◽  
Meta Analysis ◽  
Long Term Outcome ◽  
Coronary Syndrome ◽  
Cardiovascular Secondary Prevention

Abstract Background Niacin remains a therapeutic option for patients with cardiovascular disease, but recent studies have called into question the effectiveness of other HDL-C-raising drugs. We evaluated the evidence supporting current FDA-approved uses of niacin in cardiovascular prevention settings. Methods The systematic review included clinical trials involving niacin as a treatment for cardiovascular disease. The meta-analysis included randomized clinical trials reporting niacin’s effect on at least one long-term outcome: cardiovascular disease, coronary heart disease mortality, acute coronary syndrome, stroke, revascularization, major adverse cardiac events (MACE). Databases were searched up to October 2017. Study-level data were extracted and inverse-variance weighted methods were used to produce pooled risk ratios using random-effects models for between-study heterogeneity. Meta-regression analysis was used to assess the association between change in HDL-C and the log risk ratio of the pooled results. Results Out of 119 clinical trials, 17 documented niacin’s effect on at least one cardiovascular disease outcome. The meta-analysis covered 35,760 patients with history of cardiovascular disease or dyslipidemia. Cumulative evidence found no preventive effect of niacin on cardiovascular outcomes in secondary prevention. Stratified meta-analysis showed an association between niacin monotherapy and reduction of some cardiovascular events (acute coronary events, RR 0.74, 95%CI 0.58-0.96; stroke, RR 0.74, 95%CI 0.59-0.94; revascularization, RR 0.51, 95%CI 0.37-0.72). These results were mainly driven by two trials conducted in the 1970s and 1980s. Conclusions Niacin might have some use in lipid control for secondary prevention as monotherapy, perhaps in patients intolerant to statins, but evidence is from older studies on a population potentially not representative of current-day patients. Key messages Niacin might have some use for cardiovascular secondary prevention in patients intolerant to statins, but evidence is from older studies on a population not representative of current-day patients. The FDA has to review the approved indications for Niacin in cardiovascular secondary prevention.

scholarly journals Cannabinoids in the Treatment of Parkinson’s Disease

2017 ◽  
Vol 01 (04) ◽  
pp. E307-E311 ◽  
Author(s):  
Florin Gandor ◽  
Georg Ebersbach
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Single Case ◽  
Case Reports ◽  
Therapeutic Option ◽  
Case Series ◽  
Idiopathic Parkinson’S Disease ◽  
Idiopathic Parkinson's Disease

AbstractDue to the changing legal status of medical cannabis and derivatives in numerous countries, this therapeutic option has moved into the field of public debate. Neurologists treating patients with idiopathic Parkinson’s disease are increasingly confronted with questions regarding cannabis as a treatment alternative, especially for levodopa-resistant Parkinson’s symptoms. A number of single case reports and case series suggested improvement of Parkinsonian symptoms after cannabinoid intake, but the small number of available randomized clinical trials failed to reproduce the extent of these findings. Only one trial found a reduction of levodopa-induced dyskinesia with cannabinoid treatment, the remaining three trials showed no effect on Parkinsonian symptoms. This article gives an overview on the effects of cannabis, and reviews experimental and clinical trials studying the effects of cannabinoids in idiopathic Parkinson’s disease.

scholarly journals Regulación del uso de cannabis en los niños argentinos con epilepsia refractaria. Una mirada desde el derecho latinoamericano comparado / Regulation of cannabis use in argentinean children with refractory epilepsy. A view from comparative latin american l

2019 ◽  
pp. 91-106
Author(s):  
José María Palacio ◽  
Karina Rojas
Keyword(s):  
Clinical Trials ◽  
Latin American ◽  
Randomized Clinical Trials ◽  
Refractory Epilepsy ◽  
Adjunctive Treatment ◽  
Double Blind ◽  
Medicinal Use ◽  
Revisión Sistemática ◽  
The Law ◽  
The One

Muchos avances se han producido en la última década en cuánto a los tratamientos coadyuvantes para la epilepsia refractaria (ER) en niños tales como la Dieta Cetogénica (DC), los fármacos antiepilépticos (FAE) y recientemente la regulación del uso de cannabis como ley de fondo en nuestro país, a iniciado los primeros pasos en materia de ensayos clínicos en relación a esta enfermedad crónica. Objetivos: 1) Conocer la planta y sus componentes como tratamiento coadyuvante para la ER 2) Indagar a cerca de  la regulación de fondo del uso Medicinal de la planta de  cannabis y sus derivados en Argentina 3) analizar la legislación de la marihuana en el derecho comparado latinoamericano. Material  y  Métodos: se realizo una revisión sistemática de los  artículos encontrados en la literatura científica que nuclean palabras claves tales como: cannabinoides, epilepsia refractaria, niños, legislación y derecho comparado durante abril 2017 a abril 2018, en  los principales portales médicos por un lado tales como Pubmed, Medline, Lilacs  y Cochrane, como así también en los portales jurídicos sobre legislación y doctrina especializada de la Dirección de Servicios Legislativos de la Biblioteca del Congreso de la Nación Argentina. El idioma utilizado fue el ingles y español. Resultados: El avance jurídico de la ley 27.350 denominada “Uso medicinal del cannabis y sus derivados” y su decreto reglamentario 738/2017 en nuestro país, abre un nuevo escenario medico jurídico el cual permitirá fortalecer los ensayos clínicos randomizados con estudios doble-ciego, placebo controlados con el objetivo de demostrar la efectividad y seguridad de su uso en la población infantil. Los datos preliminares de la investigación sugieren que el cannabis es efectivo en un 59 % de los casos reportados en el tratamiento de los niños/as y adolescentes con ER. Sin embargo, los datos disponibles en los centros de Argentina son limitados y experimentales en una primera facie no permitiendo sacar conclusiones aún. Es meritorio destacar que varios de los países latinoamericanos fueron precursores del marco regulatorio en el uso de la marihuana medicinal y nuestro país ha receptado sus bases legislativas para dar respuestas a nuevos escenarios sociales que demanden respuestas médicas jurídicos.   Many advances have occurred in the last decade in terms of adjuvant treatments for refractory epilepsy (ER) in children such as the Ketogenic Diet (DC), antiepileptic drugs (FAE) and recently the regulation of the use of cannabis as a law of background in our country, has begun the first steps in clinical trials in relation to this chronic disease. Objectives: 1) Know the plant and its components as an adjunctive treatment for the ER 2) Inquire about the basic regulation of the medicinal use of the cannabis plant and its derivatives in Argentina 3) analyze the legislation of marijuana in the law Latin American compared. Material and Methods: a systematic review of the articles found in the scientific literature that combine keywords such as: cannabinoids, refractory epilepsy, children, legislation and law compared during April 2017 to April 2018, in the main medical portals on the one hand such as Pubmed, Medline, Lilacs and Cochrane, as well as in the legal portals on legislation and specialized doctrine of the Legislative Services Department of the Library of Congress of the Argentine Nation. The language used was English and Spanish. Results: The legal advance of the law 27,350 called “Medicinal use of cannabis and its derivatives” and its regulatory decree 738/2017 in our country, opens a new legal medical scenario which will strengthen the randomized clinical trials with double-blind studies, placebo controlled in order to demonstrate the effectiveness and safety of its use in children. Preliminary research data suggest that cannabis is effective in 59% of the cases reported in the treatment of children and adolescents with RE. However, the data available in the centers of Argentina are limited and experimental in a first facie not allowing conclusions yet. It is worth mentioning that several of the Latin American countries were precursors of the regulatory framework in the use of medical marijuana and our country has received its legislative bases to respond to new social scenarios that demand legal medical responses.

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