Pain
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Randomized Controlled Trial
Efficacy and safety of EMA401 in peripheral neuropathic pain: results of two randomised, double-blind, phase 2 studies in patients with postherpetic neuralgia and painful diabetic neuropathy.
The analgesic efficacy and safety of 2 phase 2b studies of EMA401 (a highly selective angiotensin II type 2 receptor antagonist) in patients with postherpetic neuralgia (EMPHENE) and painful diabetic neuropathy (EMPADINE) were reported. These were multicentre, randomised, double-blind treatment studies conducted in participants with postherpetic neuralgia or type I/II diabetes mellitus with painful distal symmetrical sensorimotor neuropathy. Participants were randomised 1:1:1 to either placebo, EMA401 25 mg, or 100 mg twice daily (b.i.d) in the EMPHENE and 1:1 to placebo or EMA401 100 mg b.i.d. in the EMPADINE. ⋯ Out of the planned participants, a total of 129/360 (EMPHENE) and 137/400 (EMPADINE) participants were enrolled. The least square mean reduction in numeric rating scale pain score was numerically in favour of EMA401 100 mg arm in both EMPHENE (treatment difference: -0.5 [95% confidence interval: -1.6 to 0.6; P value: 0.35]) and EMPADINE (treatment difference: -0.6 [95% confidence interval: -1.4 to 0.1; P value: 0.10]) at the end of week 12. However, as the studies were terminated prematurely, no firm conclusion could be drawn but the consistent clinical improvement in pain intensity reduction across these 2 studies in 2 different populations is worth noting.
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Randomized Controlled Trial
Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine.
Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six patients with migraine without aura were randomly allocated to receive an infusion of MaxiPost or placebo on 2 study days separated by at least 1 week. ⋯ The incidence of headache over the 12-hour observation period was higher after MaxiPost day (n = 22) than after placebo (n = 7) (P < 0.0001). We found a significant increase of VMCA and superficial temporal and radial arteries' diameter. Because BKCa channel opening initiates migraine attacks, we suggest that BKCa channel blockers could be potential candidates for novel antimigraine drugs.
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Randomized Controlled Trial
An implantable restorative-neurostimulator for refractory mechanical chronic low back pain: a randomized sham-controlled clinical trial.
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). ⋯ 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.