Pain
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial).
Neublastin (BG00010) is a first-in-class, glial cell-derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin doses (50, 150, 400, 800, and 1200 μg/kg) administered as an intravenous injection 3 times/week for 1 week in patients with chronic painful lumbosacral radiculopathy, utilizing Bayesian response-adaptive study design. Primary endpoint was change from baseline in mean 24-hour average general pain intensity over a 5-day period (week 1) after the last dose, analyzed using a Bayesian normal dynamic linear model. ⋯ The most common adverse event in all neublastin dose groups was pruritus (79% vs 10% with placebo). There was no dose-response relationship with respect to primary/secondary efficacy outcomes or incidence of pruritus, despite dose-proportional increases in serum neublastin concentrations. In conclusion, while this study showed some evidence of pain relief with neublastin, particularly at the lowest dose, there was no clear dose-response relationship for pain reduction or the most common adverse event of pruritus.
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Randomized Controlled Trial
Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.
Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. ⋯ Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.
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Randomized Controlled Trial
The relationship of sociodemographic and psychological variables to chronic pain variables in a low-income population.
Chronic pain is a pervasive condition that is complicated by economic, educational, and racial disparities. This study analyzes key factors associated with chronic pain within an understudied and underserved population. The sample is characterized by a triple disparity with respect to income, education/literacy, and racial barriers that substantially increase the vulnerability to the negative consequences of chronic pain. ⋯ Depressive symptoms and pain catastrophizing mediated the relationships between age and pain variables, whereas pain catastrophizing mediated the effects of primary literacy and poverty status. Some reversed models were equivalent to the hypothesized models, suggesting the possibility of bidirectionality. Although cross-sectional findings cannot establish causality, our results highlight the critical role psychological factors play in individuals with chronic pain and multiple health disparities.