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Abstract: Adults with chronic low back pain, disability, moderate-to-severe pain, and high fear of movement and reinjury were recruited into a trial of a novel, automated, digital therapeutics, virtual reality, psychological intervention for pain (DTxP). We conducted a 3-arm, prospective, double-blind, pilot, randomized, controlled trial comparing DTxP with a sham placebo comparator and an open-label standard care. Participants were enrolled for 6 to 8 weeks, after which, the standard care control arm were rerandomized to receive either the DTxP or sham placebo. Forty-two participants completed assessments at baseline, immediately posttreatment (6-8 weeks), 9-week, and 5-month follow-up. We found that participants in the DTxP group reported greater reductions in fear of movement and better global impression of change when compared with sham placebo and standard care post treatment. No other group differences were noted at posttreatment or follow-up. When compared with baseline, participants in the DTxP group reported lower disability at 5-month follow-up, lower pain interference and fear of movement post treatment and follow-up, and lower pain intensity at posttreatment. The sham placebo group also reported lower disability and fear of movement at 5-month follow-up compared with baseline. Standard care did not report any significant changes. There were a number of adverse events, with one participant reporting a serious adverse event in the sham placebo, which was not related to treatment. No substantial changes in medications were noted, and participants in the DTxP group reported positive gaming experiences. [ABSTRACT FROM AUTHOR]

Abstract: Chronic low back pain can be caused by impaired control and degeneration of the multifidus muscles and consequent functional instability of the lumbar spine. Available treatment options have limited effectiveness and prognosis is unfavorable. We conducted an international randomized, double-blind, sham-controlled trial at 26 multidisciplinary centers to determine safety and efficacy of an implantable, restorative neurostimulator designed to restore multifidus neuromuscular control and facilitate relief of symptoms (clinicaltrials.gov identifier: NCT02577354). Two hundred four eligible participants with refractory mechanical (musculoskeletal) chronic LBP and a positive prone instability test indicating impaired multifidus control were implanted and randomized to therapeutic (N = 102) or low-level sham (N = 102) stimulation of the medial branch of the dorsal ramus nerve (multifidus nerve supply) for 30 minutes twice daily. The primary endpoint was the comparison of responder proportions (≥30% relief on the LBP visual analogue scale without analgesics increase) at 120 days. After the primary endpoint assessment, participants in the sham-control group switched to therapeutic stimulation and the combined cohort was assessed through 1 year for long-term outcomes and adverse events. The primary endpoint was inconclusive in terms of treatment superiority (57.1% vs 46.6%; difference: 10.4%; 95% confidence interval, -3.3% to 24.1%, P = 0.138). Prespecified secondary outcomes and analyses were consistent with a modest but clinically meaningful treatment benefit at 120 days. Improvements from baseline, which continued to accrue in all outcome measures after conclusion of the double-blind phase, were clinically important at 1 year. The incidence of serious procedure- or device-related adverse events (3.9%) compared favorably with other neuromodulation therapies for chronic pain. [ABSTRACT FROM AUTHOR]

This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n = 142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single-center, double-blind, 12-week, 4-arm, parallel groups controlled clinical trial of (1) low concentration desipramine titrated to reach a serum concentration level of 15 to 65 ng/mL; (2) CBT and active placebo medication (benztropine mesylate, 0.125 mg); (3) low concentration desipramine and CBT; and (4) active benztropine placebo medication. Participants completed the Differential Description Scale and Roland Morris Disability Questionnaires before and after treatment as validated measures of outcomes in back pain intensity and disability, respectively. Participants within each condition showed significant reductions from pre-treatment to post-treatment in pain intensity (mean changes ranged from = -2.58 to 3.87, Cohen's d's = 0.46-0.84) and improvements in pain disability (mean changes = -3.04 to 4.29, Cohen's d's = 0.54-0.88). However, intent-to-treat analyses at post-treatment showed no significant differences between any condition, with small effect sizes ranging from 0.06 to 0.27. The results from this clinical trial did not support the hypothesis that desipramine, CBT, or their combination would be statistically superior to an active medicine placebo for reducing chronic back pain intensity or disability. Key limitations included recruiting 71% of the planned sample size and use of multiple inclusion/exclusion criteria that may limit generalizability to broader populations of patients with chronic back pain. [ABSTRACT FROM AUTHOR]

Despite optimal medical management (OMM), low back pain (LBP) can be disabling, particularly after spinal surgery. Spinal cord stimulation (SCS) is effective in reducing neuropathic leg pain; however, evidence is limited for LBP. This prospective, open-label, parallel-group trial randomized (1:1) failed back surgery syndrome (FBSS) patients with predominant LBP to SCS plus OMM (SCS group) or OMM alone (OMM group) at 28 sites in Europe and the Americas. If trial stimulation was successful, a multicolumn SCS system was implanted. Outcomes were assessed at baseline (before randomization) and at 1, 3, 6, and 12 months after randomization. Patients could change treatment groups at 6 months. The primary outcome was the proportion of patients with ≥50% reduction in LBP (responder) at 6 months. Secondary outcomes included change in pain intensity, functional disability, and health-related quality of life (HRQoL). The results are posted at ClinicalTrials.gov under registration number NCT01697358. In the intent-to-treat analysis, there were more responders in the SCS group than in the OMM group (13.6%, 15/110 vs 4.6%, 5/108, difference 9% with 95% confidence interval 0.6%-17.5%, P = 0.036) at 6 months. The SCS group improved in all secondary outcomes compared with the OMM group. The OMM group only improved in HRQoL. In the SCS group, 17.6% (18/102) experienced SCS-related adverse events through 6 months, with 11.8% (12/102) requiring surgical reintervention. Adding multicolumn SCS to OMM improved pain relief, HRQoL, and function in a traditionally difficult-to-treat population of failed back surgery syndrome patients with predominant LBP. Improvements were sustained at 12 and 24 months. [ABSTRACT FROM AUTHOR]

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. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 μg once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. 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. [ABSTRACT FROM AUTHOR]

Opioid analgesics are commonly used for the treatment of chronic low back pain (CLBP); however, abuse potential is a major concern. This study used a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal study design to evaluate the safety, tolerability, and analgesic efficacy of an abuse-deterrent formulation of extended-release oxycodone, Xtampza ER, in opioid-naive and opioid-experienced adults with moderate-to-severe CLBP. Patients entered an open-label titration phase (N = 740); those who were successfully titrated on Xtampza ER (≥40 to ≤160 mg oxycodone hydrochloride equivalent per day) were randomized to active drug (N = 193) or placebo (N = 196) for 12 weeks. Primary efficacy results showed a statistically significant difference in average pain intensity from randomization baseline to treatment week 12 between the Xtampza ER and placebo groups (mean [±SE], -1.56 [0.267]; P < 0.0001). All sensitivity analyses results supported the primary result of the study. Secondary efficacy outcomes indicated that Xtampza ER vs placebo had more patients with improvement in patient global impression of change (26.4% vs 14.3%; P < 0.0001), longer time-to-exit from the study (58 vs 35 days; P = 0.0102), and a greater proportion of patients with ≥30% (49.2% vs 33.2%; P = 0.0013) and ≥50% (38.3% vs 24.5%; P = 0.0032) improvement in pain intensity. There was less rescue medication (acetaminophen) use in the Xtampza ER treatment group than in the placebo group. Xtampza ER had an adverse event profile consistent with other opioids and was well tolerated; no new safety concerns were identified. In conclusion, Xtampza ER resulted in clinically and statistically significant efficacy in patients with CLBP. [ABSTRACT FROM AUTHOR]