A Randomized, Placebo-controlled Trial of the Analgesic Efficacy and Safety of the p38 MAP Kinase Inhibitor, Losmapimod, in Patients With Neuropathic Pain From Lumbosacral Radiculopathy

Abstract Background Acute pharyngitis and tonsillitis are common respiratory diseases for which children seek medical care. Their main clinical manifestation is sore throat which interferes with patients’ quality of life. However, there is no proven effective or safe method to treat it. It is necessary to find an excellent strategy to reduce sore throat and reduce the burden of acute illness. We designed the randomized controlled trial with the characteristics of traditional Chinese medicine (TCM) to determine the clinical positioning of Kai-Hou-Jian spray (children’s type) (KHJS) through evidence-based research. This trial aims to evaluate the immediate analgesic efficacy of KHJS on sore throat caused by acute pharyngitis and tonsillitis (wind-heat syndrome/heat exuberance in lung and stomach syndrome) in children and to observe its safety. Methods/design This is a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. It will include 240 children with acute pharyngitis/tonsillitis from 7 study sites across China. All participants are randomly assigned to two parallel treatment groups, one with KHJS and the other with placebo sprays, for 5 consecutive days. The primary outcome is the time of analgesic onset. Secondary outcomes include duration of analgesic effect, area under time curve of 0–3 h Wong-Baker FACES Pain Rating Scale (WBS) score (AUC0-3 h), rate of analgesic onset, rate of disappearance of sore throat, changes of WBS score (in days), effective rate of pharyngeal signs, and effective rate of TCM syndrome. The incidence of adverse events during the trial is the primary safety outcome. In addition, vital signs and laboratory tests before and after medication are monitored. Discussion To our knowledge, this will be the first clinical trial to explore the immediate analgesic efficacy of a Chinese patent medicine spray for acute pharyngitis/tonsillitis induced sore throat in children in a multicenter, randomized, double-blinded, parallel-group, placebo-controlled manner. Not only might it prove the efficacy and safety of KHJS in the treatment of sore throat caused by acute pharyngitis/tonsillitis in children, but it might also provide evidence for the treatment of acute sore throat with Chinese herbal medicine. Trial registration A multicenter, randomized, double-blind, very low-dose, parallel controlled trial for the immediate analgesic effect and safety of Kai-Hou- Jian spray (children's type) in the treatment of sore throat caused by acute pharyngitis and tonsillitis in children. Chinese Clinical Trial Registry ChiCTR2000031599. Registered on 5 April 2020

Download Full-text

Safety, pharmacokinetics, and pharmacodynamics of single doses of an oral p38 MAP kinase inhibitor (BIRB 796 BS) in healthy human males a placebo-controlled, randomised study, double blinded at each dose level

Journal of Allergy and Clinical Immunology ◽

10.1016/s0091-6749(02)81294-5 ◽

2002 ◽

Vol 109 (1) ◽

pp. S67-S67 ◽

Cited By ~ 7

Author(s):

Abhya Gupta ◽

Chan-Loi Yong ◽

Jeffrey B Madwed ◽

Hildegard Staehle ◽

Chester C Wood

Keyword(s):

Map Kinase ◽

Dose Level ◽

Kinase Inhibitor ◽

P38 Map Kinase ◽

Pharmacokinetics And Pharmacodynamics ◽

Healthy Human ◽

Randomised Study ◽

Double Blinded

Download Full-text

Selective Regulation of T Cell IL-5 Synthesis by OM-01, JTE-711 and p38 MAP Kinase Inhibitor: Independent Control of Th2 Cytokines, IL-4 and IL-5

International Archives of Allergy and Immunology ◽

10.1159/000053702 ◽

2001 ◽

Vol 124 (1-3) ◽

pp. 172-175 ◽

Cited By ~ 2

Author(s):

Akio Mori ◽

Hirokazu Okudaira ◽

Noriaki Kobayashi ◽

Kazuo Akiyama

Keyword(s):

T Cell ◽

Map Kinase ◽

Kinase Inhibitor ◽

P38 Map Kinase ◽

Th2 Cytokines ◽

Independent Control

Download Full-text

An Open-Label, Analgesic Efficacy and Safety of Pituitary Radiosurgery for Patients With Opioid-Refractory Pain: Study Protocol for a Randomized Controlled Trial

Neurosurgery ◽

10.1093/neuros/nyx363 ◽

2017 ◽

Vol 83 (1) ◽

pp. 146-153 ◽

Cited By ~ 2

Author(s):

Pierre-Yves Borius ◽

Stéphanie Ranque Garnier ◽

Karine Baumstarck ◽

Frédéric Castinetti ◽

Anne Donnet ◽

...

Keyword(s):

Quality Of Life ◽

Pain Relief ◽

Cancer Pain ◽

Controlled Trial ◽

Analgesic Efficacy ◽

Standards Of Care ◽

Control Group ◽

Efficacy And Safety ◽

Open Label

Abstract BACKGROUND Hypophysectomy performed by craniotomy or percutaneous techniques leads to complete pain relief in more than 70% to 80% of cases for opioid refractory cancer pain. Radiosurgery could be an interesting alternative approach to reduce complications. OBJECTIVE To assess the analgesic efficacy compared with standard of care is the primary goal. The secondary objectives are to assess ophthalmic and endocrine tolerance, drug consumption, quality of life, and mechanisms of analgesic action. METHODS The trial is multicenter, randomized, prospective, and open-label with 2 parallel groups. This concerns patients in palliative care suffering from nociceptive or mixed cancer pain, refractory to standard opioid therapy. Participants will be randomly assigned to the control group receiving standards of care for pain according to recommendations, or to the experimental group receiving a pituitary GammaKnife (Elekta, Stockholm, Sweden) radiosurgery (160 Gy delivered in pituitary gland) associated with standards of care. Evaluation assessments will be taken at baseline, day0, day4, day7, day14, day28, day45, month3, and month6. EXPECTED OUTCOMES We could expect pain improvement in 70% to 90% of cases at day4. In addition we will assess the safety of pituitary radiosurgery in a vulnerable population. The secondary endpoints could show decay of opioid consumption, good patient satisfaction, and improvement of the quality of life. DISCUSSION The design of this study is potentially the most appropriate to demonstrate the efficacy and safety of radiosurgery for this new indication. New recommendations could be obtained in order to improve pain relief and quality of life.

Download Full-text

Pharmacological Management of Chronic Neuropathic Pain – Consensus Statement and Guidelines from the Canadian Pain Society

Pain Research and Management ◽

10.1155/2007/730785 ◽

2007 ◽

Vol 12 (1) ◽

pp. 13-21 ◽

Cited By ~ 343

Author(s):

DE Moulin ◽

AJ Clark ◽

I Gilron ◽

MA Ware ◽

CPN Watson ◽

...

Keyword(s):

Neuropathic Pain ◽

Controlled Trial ◽

Analgesic Efficacy ◽

Opioid Analgesics ◽

Ease Of Use ◽

Control Group ◽

Pharmacological Management ◽

Randomized Controlled ◽

Analgesic Agents ◽

Third Line

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

Download Full-text

p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction

Journal of Applied Physiology ◽

10.1152/japplphysiol.00171.2004 ◽

2005 ◽

Vol 98 (1) ◽

pp. 77-82 ◽

Cited By ~ 6

Author(s):

Hong Kan ◽

Dale Birkle ◽

Abnash C. Jain ◽

Conard Failinger ◽

Sherry Xie ◽

...

Keyword(s):

Map Kinase ◽

Cardiac Myocyte ◽

Kinase Inhibitor ◽

Ventricular Myocytes ◽

Myocardial Dysfunction ◽

P38 Map Kinase ◽

Border Detection ◽

Rat Ventricular Myocytes ◽

Adult Rat ◽

Fractional Shortening

Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls + R (45.8 ± 3.9 vs. 61.9 ± 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 ± 0.8 vs. 12.7 ± 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol ( P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans.

Download Full-text