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1.
Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine in Pain Reduction and Functional Capacity in Osteoarthritis Patients.
Puigdellivol, J, Comellas Berenger, C, Pérez Fernández, MÁ, Cowalinsky Millán, JM, Carreras Vidal, C, Gil Gil, I, Martínez Pagán, J, Ruiz Nieto, B, Jiménez Gómez, F, Comas Figuerola, FX, et al
Journal of dietary supplements. 2019;(4):379-389
Abstract
This observational, open, multicenter clinical trial with a single treatment group aimed to evaluate the effectiveness of a dietary supplement whose main ingredients are hydrolyzed gelatin, chondroitin sulfate, glucosamine sulfate, and devil's claw and bamboo extracts for pain reduction and improvement of functional capacities in patients with osteoarthritis (OA) of the knee and/or hip (REDART study). In all, 130 patients with OA recruited from Spanish hospitals received the dietary supplement for 6 months. The primary outcome was the patients' global assessment of pain in the affected joint as measured with a visual analogue scale (VAS). Other outcome measurements included the Lequesne Functional Index (subindexes for pain/discomfort, distance walked, and daily living) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC; subindexes for pain, stiffness, and physical function). Scores were taken at months 3 and 6 of the treatment. Patients (N = 78) showed a reduction of pain of 3.77 ± 1.77 points after 6 months (p < .0001) in the VAS. The total reduction in the Lequesne Functional Index was 6.30 ± 4.08 points after 6 months (p < .0001), with significant reductions in all subindexes of the scale. A similar pattern was found for the WOMAC index, with an overall reduction of 22.49 ± 14.03 points after 6 months (p < .0001) and significant reductions in all subindexes. No major adverse events were noted during the treatment. This exploratory study shows that treatment with the dietary supplement significantly reduces pain and improves locomotor function in patients with OA of the knee and/or hip.
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2.
GaPP2, a multicentre randomised controlled trial of the efficacy of gabapentin for the management of chronic pelvic pain in women: study protocol.
Vincent, K, Baranowski, A, Bhattacharya, S, Birch, J, Cheong, Y, Cregg, R, Daniels, J, Hewitt, CA, Macfarlane, GJ, Middleton, L, et al
BMJ open. 2018;(1):e014924
Abstract
INTRODUCTION Chronic pelvic pain (CPP) affects more than 1 million UK women with associated healthcare costs of £158 million annually. Current evidence supporting interventions when no underlying pathology is identified is very limited and treatment is frequently inadequate. Gabapentin (a GABA analogue) is efficacious and often well tolerated in other chronic pain conditions. We have completed a successful pilot randomised controlled trial Gabapentin for Pelvic Pain 1 (GaPP1) and here describe the protocol for our definitive multicentre trial to assess the efficacy of gabapentin in the management of CPP in women Gabapentin for Pelvic Pain 2 (GaPP2). METHODS AND ANALYSIS We plan to perform a double-blind placebo-controlled randomised multicentre clinical trial, recruiting 300 women with CPP from up to 40 National Health Service hospitals within the UK. After randomisation, women will titrate their medication (gabapentin or placebo) over a 4-week period to a maximum of 2700 mg or placebo equivalent and will then maintain a stable dose for a 12-week period. Response to treatment will be monitored with validated questionnaires and coprimary outcome measures of average and worst pain scores will be employed. The primary objective is to test the hypothesis that treatment with gabapentin has the potential to provide an effective oral treatment to alleviate pain in women with CPP in the absence of any obvious pelvic pathology. ETHICS AND DISSEMINATION Ethical approval has been obtained from the Coventry and Warwick Research Ethics Committee (REC 15/WM/0036). Data will be presented at international conferences and published in peer-reviewed journals. We will make the information obtained from the study available to the public through national bodies and charities. TRIAL REGISTRATION NUMBER ISRCTN77451762; Pre-results.
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3.
Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.
Cremon, C, Stanghellini, V, Barbaro, MR, Cogliandro, RF, Bellacosa, L, Santos, J, Vicario, M, Pigrau, M, Alonso Cotoner, C, Lobo, B, et al
Alimentary pharmacology & therapeutics. 2017;(7):909-922
Abstract
BACKGROUND Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.
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4.
Treatment in carbon monoxide poisoning patients with headache: a prospective, multicenter, double-blind, controlled clinical trial.
Ocak, T, Tekin, E, Basturk, M, Duran, A, Serinken, M, Emet, M
The American journal of emergency medicine. 2016;(11):2140-2145
Abstract
BACKGROUND There is a lack of specificity of the analgesic agents used to treat headache and underlying acute carbon monoxide poisoning. OBJECTIVE To compare effectiveness of "oxygen alone" vs "metoclopramide plus oxygen" vs "metamizole plus oxygen" therapy in treating carbon monoxide-induced headache. DESIGN A prospective, multicenter, double-blind, controlled trial. SETTING Three emergency departments in Turkey. POPULATION Adult carbon monoxide poisoning patients with headache. METHODS A total of 117 carbon monoxide-intoxicated patients with headache were randomized into 3 groups and assessed at baseline, 30 minutes, 90 minutes, and 4 hours. MAIN OUTCOME MEASURE The primary outcome was patient-reported improvement rates for headache. Secondary end points included nausea, need for rescue medication during treatment, and reduction in carboxyhemoglobin levels. RESULTS During observation, there was no statistical difference between drug type and visual analog scale score change at 30 minutes, 90 minutes, or 4 hours, for either headache or nausea. No rescue medication was needed during the study period. The reduction in carboxyhemoglobin levels did not differ among the 3 groups. CONCLUSION The use of "oxygen alone" is as efficacious as "oxygen plus metoclopramide" or "oxygen plus metamizole sodium" in the treatment of carbon monoxide-induced headache.
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5.
Uridine monophosphate, folic acid and vitamin B12 in patients with symptomatic peripheral entrapment neuropathies.
Negrão, L, Nunes, P, ,
Pain management. 2016;(1):25-9
Abstract
BACKGROUND Carpal tunnel syndrome is the most common type of peripheral entrapment neuropathy. PATIENTS & METHODS We performed an exploratory, open-label, multicenter, observational study of 48 patients with peripheral entrapment neuropathy. Patients received a daily capsule of uridine monophosphate, folic acid + vitamin B12 for 2 months and were evaluated using the Pain DETECT questionnaire. RESULTS The global score for pain decreased from 17.3 ± 5.9 at baseline to 10.3 ± 6.1 at the final evaluation (p < 0.001). Concomitant analgesic and anti-inflammatory treatment was stopped or the dose reduced in 77.4% of patients. CONCLUSION Uridine monophosphate + folic acid + vitamin B12 reduced total pain score, intensity and characterization of pain and associated symptoms. These results should be tested in a well-designed, adequately powered randomized controlled trial.
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6.
Consistency of return to normal function, productivity, and satisfaction following migraine attacks treated with sumatriptan/naproxen sodium combination.
Landy, SH, Cady, RK, Nelsen, A, White, J, Runken, MC
Headache. 2014;(4):640-54
Abstract
OBJECTIVES To assess the consistency of improved functioning, productivity, and medication satisfaction in migraines treated with a single tablet of sumatriptan 85 mg/naproxen sodium 500 mg (S/NS) using an early intervention approach. METHODS Two randomized, double-blind, placebo-controlled, 4-period crossover, multi-attack, multi-center, outpatient studies of moderate to severe adult migraineurs were conducted to compare S/NS with placebo. Participants recorded outcome assessments in a diary during the 24 hours following study medication. Analyses were conducted on the intent-to-treat population who treated at least 1 attack. Statistical significance between treatment groups used analysis of variance repeated measures models and the intent-to-treat population. There were no corrections for multiplicity. RESULTS Almost half (48.5%) of migraineurs treated with S/NS returned to normal functioning at 2 hours and 73.3% at 4 hours postdose, compared with 28.7% (2 hours) and 43.3% (4 hours) of placebo-treated attacks. Total productivity loss over the 24 hours postdose was significantly reduced following S/NS treatment (2.5 hours on average) compared with placebo (4.0 hours). Sumatriptan/naproxen treatment resulted in significantly higher medication satisfaction scores on the efficacy, functionality, and total efficacy subscales compared with placebo in all attacks in both studies. Sumatriptan/naproxen treatment also provided significantly greater ease of use in 7 of the 8 attacks. Although tolerability was high in both treatment groups (over 90%), the placebo group was significantly less bothered by side effects in 6 of 8 attacks. CONCLUSION Results from these 2 randomized, double-blind, placebo-controlled, multi-attack, crossover studies demonstrated the rapid and consistent restoration of patients' functioning, the consistent reduction in productivity loss, and high satisfaction ratings from patients treating multiple migraine attacks with S/NS using an early intervention approach.
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7.
Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: a randomized study.
Tullo, V, Valguarnera, F, Barbanti, P, Cortelli, P, Sette, G, Allais, G, d'Onofrio, F, Curone, M, Zava, D, Pezzola, D, et al
Cephalalgia : an international journal of headache. 2014;(6):434-45
Abstract
BACKGROUND Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief. METHODS A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment. RESULTS The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies ( P < 0.05). Proportions of SPF at 24 hours were 24% (22/93) for Frova, 43% (41/95) for FroDex25 ( P < 0.001) and 42% (38/91) for FroDex37.5 ( P < 0.05). SPF at 48 hours was 23% (21/93) with Frova, 36% (34/95) with FroDex25 and 33% (30/91) with FroDex37.5 ( P = NS). Recurrence was similar for Frova (22%, 6/27), FroDex25 (29%, 14/48) and FroDex37.5 (28%, 13/46) ( P = NS), meaning a lack of improvement with the combination therapy. Statistical adjustment for multiple comparisons was not performed. No statistically significant differences were reported in the occurrence of total and drug-related adverse events. FroDex25 and FroDex37.5 showed a similar efficacy both for primary and secondary end points. There did not seem to be a dose response curve for the addition of dexketoprofen. CONCLUSION FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.
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8.
Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain.
Uehleke, B, Müller, J, Stange, R, Kelber, O, Melzer, J
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2013;(11):980-4
Abstract
STUDY OBJECTIVE Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). PATIENTS AND METHODS The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. RESULTS Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. CONCLUSION These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.
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9.
Clinical relevance of efficacy endpoints in OTC headache trials.
Pageler, L, Diener, HC, Pfaffenrath, V, Peil, H, Aicher, B
Headache. 2009;(5):646-54
Abstract
OBJECTIVE This analysis evaluates and ranks efficacy endpoints often used in headache trials concerning their clinical relevance in relation to the patient-related criterion "global assessment of overall efficacy" based on data gained in a large trial investigating different over-the-counter drugs in the treatment of headache. BACKGROUND The original study showed a significant superiority of the fixed combination of acetylsalicylic acid+paracetamol+caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. METHODS For 1734 patients included in the efficacy analysis we investigated the correlation of patient's global efficacy assessment with the endpoints "time to 50% pain relief" (primary endpoint), "time to be pain-free," pain intensity difference, sum of pain intensity difference, and extent of impairment of daily activities. Patients recorded pain intensity on a visual analog scale. Efficacy, tolerability, and extent of impairment of daily activity were assessed on verbal rating scales.A logistic regression, proportional odds model was adapted to the time to event data. RESULTS The highest correlation with patient's global efficacy assessment was demonstrated for the primary endpoint time to 50% pain relief (r = 0.6727) and the sum of pain intensity difference (r = 0.7037). The frequency distribution of patient's global efficacy assessment depended primarily on the time to 50% pain relief and similarly, but to a somewhat lesser extent, on the reduction of pain intensity to 10 mm as assessed on the visual analog scale. More than 86% of the patients assessed efficacy as very good or good when their pain was reduced by 50% at least within 1 hour after drug intake. The patients accept a longer time span than 2 hours for reaching no pain to give a positive global evaluation of efficacy.
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10.
Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study.
Hagen, NA, du Souich, P, Lapointe, B, Ong-Lam, M, Dubuc, B, Walde, D, Love, R, Ngoc, AH, ,
Journal of pain and symptom management. 2008;(4):420-9
Abstract
Cancer pain is a serious public health issue and more effective treatments are needed. This study evaluates the analgesic activity of tetrodotoxin, a highly selective sodium channel blocker. This randomized, placebo-controlled, parallel design study of subcutaneous tetrodotoxin, in patients with moderate or severe unrelieved cancer pain persisting despite best available treatment, involved 22 centers across Canada. The design called for tetrodotoxin administered subcutaneously over Days 1-4 with a period of observation to Day 15 or longer. All patients could enroll into an open-label extension efficacy and safety trial. The primary endpoint was the proportion of analgesic responders in each treatment arm. Eighty-two patients were randomized, and results on 77 were available for analysis. There was a nonstatistically significant trend toward more responders in the active treatment arm based on the primary endpoint (pain intensity difference). However, analysis of secondary endpoints, and an exploratory post hoc analysis, suggested there may be a robust analgesic effect if a composite endpoint is used, including either fall in pain level, or fall in opioid dose, plus improvement in quality of life. Most patients described transient perioral tingling or other mild sensory phenomena within about an hour of each treatment. Nausea and other toxicities were generally mild, but one patient experienced a serious, adverse event, truncal and gait ataxia. This trial suggests tetrodotoxin may potentially relieve moderate to severe, treatment-resistant cancer pain in a large proportion of patients, and often for prolonged periods following treatment, but further study is warranted using a composite primary endpoint.