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1.
Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.
Baba, M, Matsui, N, Kuroha, M, Wasaki, Y, Ohwada, S
Journal of diabetes investigation. 2020;(3):693-698
Abstract
AIMS/INTRODUCTION Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an α2 δ ligand with a slower dissociation for α2 δ-1 versus α2 δ-2 subunits, showed efficacy and safety in a randomized, double-blind, placebo-controlled, 14-week study in Asian patients with DPNP. This open-label extension study evaluated the long-term safety and efficacy of mirogabalin in Asian patients with DPNP. MATERIAL AND METHODS This 52-week open-label extension study was carried out in Japan, Korea and Taiwan in patients with DPNP. Patients received mirogabalin, initiated at 5 mg twice daily and increased to a flexible maintenance dosage of 10 or 15 mg twice daily. Adverse events were monitored throughout the study. Patients provided a self-assessment of pain using the Short-Form McGill Pain Questionnaire. RESULTS Of the 214 patients who entered the study, 172 (80.4%) completed the extension study. Of 172 patients who completed the study, 149 received the highest dosage of mirogabalin (15 mg twice daily). The most common treatment-emergent adverse events were nasopharyngitis, diabetic retinopathy, peripheral edema, somnolence, diarrhea, increased weight and dizziness. Most treatment-emergent adverse events were mild or moderate in severity. The incidence of treatment-emergent adverse events leading to treatment discontinuation was 13.1%. The visual analog scale and all other Short-Form McGill Pain Questionnaire subscales (sensory score, affective score, total score and present pain intensity) generally decreased over time from baseline until week 52. CONCLUSIONS This extension study showed the safety and efficacy of a long-term flexible dosing regimen of mirogabalin 10 or 15 mg twice daily in patients with DPNP.
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2.
Diabetic polyneuropathy is a risk factor for decline of lower extremity strength in patients with type 2 diabetes.
Nomura, T, Ishiguro, T, Ohira, M, Ikeda, Y
Journal of diabetes investigation. 2018;(1):186-192
Abstract
AIMS/INTRODUCTION The present study elucidated the effect of diabetic polyneuropathy (DPN) on lower extremity strength in a wide age range of type 2 diabetes patients. MATERIALS AND METHODS Participants (n = 1,442) were divided into three age groups (30-49 years, 50-69 years and 70-87 years), and comparisons were made separately for each sex. Lower extremity strength was measured in terms of knee extension force (KEF) with a hand-held dynamometer. KEF was compared according to the presence or absence of DPN. Furthermore, the effect of DPN on KEF with other diabetic complications (diabetic retinopathy and diabetic nephropathy), diabetes status (diabetes duration and glycated hemoglobin) and habitual behavior (regular exercise, smoking and drinking behaviors) as explanatory variables was analyzed using multiple regression analysis in several models. RESULTS The frequency of DPN differed among age groups, ranging from 14.3 to 49.6%, and increasing with age. There was no significant difference in KEF between patients aged 30-49 years with and without DPN. However, among both men and women aged 50-69 years and 70-87 years, patients with DPN showed significantly diminished KEF (11.0-12.9% and 11.9-16.6%, respectively) compared with those without DPN (P < 0.01-0.001). In women aged 50-69 years and 70-87 years, and in men aged 50-69 years, DPN was a significant explanatory variable for KEF in all multiple regression analysis models. CONCLUSION DPN might reinforce a KEF decline in middle-aged and elderly type 2 diabetes patients.
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3.
NerveCheck: An inexpensive quantitative sensory testing device for patients with diabetic neuropathy.
Ponirakis, G, Odriozola, MN, Odriozola, S, Petropoulos, IN, Azmi, S, Fadavi, H, Alam, U, Asghar, O, Marshall, A, Miro, A, et al
Diabetes research and clinical practice. 2016;:101-7
Abstract
AIMS: Sensory neuropathy is central to the development of painful neuropathy, and foot ulceration in patients with diabetes. Currently, available QST devices take considerable time to perform and are expensive. NerveCheck is the first inexpensive ($500), portable QST device to perform both vibration and thermal testing and hence evaluate diabetic peripheral neuropathy (DPN). This study was undertaken to establish the reproducibility and diagnostic validity of NerveCheck for detecting neuropathy. METHODS 130 subjects (28 with DPN, 46 without DPN and 56 control subjects) underwent QST assessment with NerveCheck; vibration perception and thermal testing. DPN was defined according to the Toronto criteria. RESULTS NerveCheck's intra correlation coefficient for vibration, cold and warm sensation testing was 0.79 (95% LOA: -4.20 to 6.60), 0.86 (95% LOA: -1.38 to 2.72) and 0.71 (95% LOA: -2.36 to 3.83), respectively. The diagnostic accuracy (AUC) for vibration, cold and warm sensation testing was 86% (SE: 0.038, 95% CI 0.79-0.94), 79% (SE: 0.058, 95% CI 0.68-0.91) and 72% (SE: 0.058, 95% CI 0.60-0.83), respectively. CONCLUSIONS This study shows that NerveCheck has good reproducibility and comparable diagnostic accuracy to established QST equipment for the diagnosis of DPN.
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4.
Prospective evaluation of the effect of short-term oral vitamin d supplementation on peripheral neuropathy in type 2 diabetes mellitus.
Shehab, D, Al-Jarallah, K, Abdella, N, Mojiminiyi, OA, Al Mohamedy, H
Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2015;(3):250-6
Abstract
OBJECTIVE We aimed to assess the efficacy of short-term oral vitamin D supplementation on peripheral neuropathy in patients with type 2 diabetes. MATERIALS AND METHODS This prospective, placebo-controlled trial included 112 type 2 diabetic patients with diabetic peripheral neuropathy (DPN) and vitamin D [25(OH)D] deficiency. Patients were sequentially assigned to a treatment group (n = 57) and a placebo group (n = 55). DPN was assessed using a neuropathy symptom score (NSS), a neuropathy disability score (NDS) and a nerve conduction study (NCS). Vitamin D status was determined by measuring the serum total 25(OH)D concentration. Patients received either oral vitamin D3 capsules or starch capsules once weekly for 8 weeks. The primary outcome was changes in NSS and NDS from baseline. The secondary outcome was changes in the NCS result. RESULTS Serum 25(OH)D concentrations significantly improved after oral vitamin D supplementation in the treatment group when compared to the placebo group (32.8 ± 23.7 vs. 1.1 ± 3.6, p < 0.0001). Similarly, the improvement in NSS values was significantly greater in the treatment group than in the placebo group (-1.49 ± 1.37 vs. -0.20 ± 0.59, p < 0.001). No improvement was observed for NDS and NCS between the 2 groups after treatment. CONCLUSION Short-term oral vitamin D3 supplementation improved vitamin D status and the symptoms of neuropathy in patients with type 2 diabetes.
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Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Villegas-Rivera, G, Román-Pintos, LM, Cardona-Muñoz, EG, Arias-Carvajal, O, Rodríguez-Carrizalez, AD, Troyo-Sanromán, R, Pacheco-Moisés, FP, Moreno-Ulloa, A, Miranda-Díaz, AG
Oxidative medicine and cellular longevity. 2015;:756294
Abstract
OBJECTIVE To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN). METHODS We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis. RESULTS LPO levels were reduced in both statin arms after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores. DISCUSSION EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.
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6.
Prevalence and correlates of diabetic peripheral neuropathy in a Saudi Arabic population: a cross-sectional study.
Wang, DD, Bakhotmah, BA, Hu, FB, Alzahrani, HA
PloS one. 2014;(9):e106935
Abstract
The purpose of this cross-sectional study was to investigate the prevalence and correlates of diabetic peripheral neuropathy (DPN) in a Saudi population. The study population consisted of 552 diabetic participants with an average age of 53.4 years. Among this population, 62.7% were male and 94.9% had type 2 diabetes. The average body mass index was 31.1 kg/m2. DPN was diagnosed based on a combination of reduced vibration perception measured by neurothesiometer and/or reduced light touch perception evaluated by the 10-g Semmes-Weinstein monofilament, as well as neurological symptoms. Information on socio-demographic variables, smoking status, duration of diabetes, and medications was obtained through interviews by physicians. Body weight, height, waist circumference, blood pressure and clinical markers were assessed following standard procedures. The prevalence of DPN in this population was 19.9% (95% CI, 16.7%-23.5%). In the multivariable analyses, longer duration of diabetes [odds ratio (OR) for every 5-year increase, 2.49, 95% CI, 1.75-3.53], abdominal obesity (OR, 2.53, 95% CI, 1.41-4.55), and higher levels of fasting blood glucose (OR for every 1 mmol/L increase, 1.05, 95% CI, 0.99-1.12), creatinine (OR for every 10 µmol/L increase, 1.07, 95% CI, 0.99-1.14) and white blood cell count (OR for every 106/L increase, 1.08, 95% CI, 1.01-1.16) were associated with higher odds of DPN, while oral hypoglycemic medication use was associated with a lower odds of DPN (OR, 0.47, 95% CI, 0.26-0.85). In this large Saudi population, several correlates for DPN, in addition to glycemic control and diabetes duration, were identified, including abdominal obesity, creatinine and white blood cell count.
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7.
A prospective multi-centric open clinical trial of homeopathy in diabetic distal symmetric polyneuropathy.
Nayak, C, Oberai, P, Varanasi, R, Baig, H, Ch, R, Reddy, GR, Devi, P, S, B, Singh, V, Singh, VP, et al
Homeopathy : the journal of the Faculty of Homeopathy. 2013;(2):130-8
Abstract
OBJECTIVES To evaluate homeopathic treatment in the management of diabetic distal symmetric polyneuropathy. METHODS A prospective multi-centric clinical observational study was carried out from October 2005 to September 2009 by Central Council for Research in Homeopathy (CCRH) (India) at its five institutes/units. Patients suffering from diabetes mellitus (DM) and presenting with symptoms of diabetic polyneuropathy (DPN) were screened, investigated and were enrolled in the study after fulfilling the inclusion and exclusion criteria. Patients were evaluated by the diabetic distal symmetric polyneuropathy symptom score (DDSPSS) developed by the Council. A total of 15 homeopathic medicines were identified after repertorizing the nosological symptoms and signs of the disease. The appropriate constitutional medicine was selected and prescribed in 30, 200 and 1 M potency on an individualized basis. Patients were followed up regularly for 12 months. RESULTS Out of 336 patients (167 males and 169 females) enrolled in the study, 247 patients (123 males and 124 females) were analyzed. All patients who attended at least three follow-up appointments and baseline curve conduction studies were included in the analysis.). A statistically significant improvement in DDSPSS total score (p = 0.0001) was found at 12 months from baseline. Most objective measures did not show significant improvement. Lycopodium clavatum (n = 132), Phosphorus (n = 27) and Sulphur (n = 26) were the medicines most frequently prescribed. Adverse event of hypoglycaemia was observed in one patient only. CONCLUSION This study suggests homeopathic medicines may be effective in managing the symptoms of DPN patients. Further studies should be controlled and include the quality of life (QOL) assessment.
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8.
Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study.
Thisted, RA, Klaff, L, Schwartz, SL, Wymer, JP, Culligan, NW, Gerard, G, Pope, LE, Berg, JE
Clinical therapeutics. 2006;(10):1607-18
Abstract
BACKGROUND Pain associated with diabetic peripheral neuropathy (DPN) has a substantial negative impact on patients' quality of life. OBJECTIVES The primary objective of this study was to evaluate the tolerability of capsules containing dextromethorphan (DM) and quinidine (Q) in patients with painful DPN. A secondary objective was to perform a preliminary assessment of the efficacy of DM/Q in this patient population. METHODS This was a multicenter, open-label, dose-escalation study. Eligible patients were aged between 18 and 80 years, had a confirmed diagnosis of diabetes with acceptable glycemic control, had been receiving established diabetic therapy for at least 3 months, and had a clinical diagnosis of distal symmetric sensory neuropathy with daily DPN-associated pain for the previous 3 months. On study entry, patient-rated diabetic pain had to be moderate or greater. Patients who met the inclusion criteria underwent a 2-week washout period during which all analgesics were discontinued, followed by 29 days of treatment with capsules containing DM 30 mg and Q 30 mg (DM30/Q30), beginning with 1 capsule/d and escalating at approximately 1-week intervals, as tolerated, to a maximum dose of 4 capsules/d (DM120/Q120). Tolerability was assessed based on adverse events and changes in clinical and laboratory parameters and nerve conduction velocity. Preliminary efficacy assessments included changes from baseline in scores on the pain intensity rating scale (PIRS), pain relief rating scale (PRRS), peripheral neuropathy quality-of-life instrument, and patients' diary assessments of sleep, present pain intensity, pain, and activity. RESULTS The study included 36 men and women (mean age, 58 years; mean body mass index, 32.8 kg/m(2)). Of the 33 subjects who completed the study, 23 (69.7%) did so at the highest permitted dose (DM120/Q120). The most commonly reported adverse events (occurring in > or =5% of subjects) were nausea (27.8%), dizziness (25.0%), and headache (25.0%). Three patients experienced 5 serious adverse events, only 1 of which was considered possibly related to study drug. The most commonly occurring laboratory abnormalities (involving glycosylated hemoglobin, serum glucose, triglycerides, and cholesterol) were considered typical of a population with diabetes. Improvements from baseline in scores on the PIRS, PRRS, and other exploratory efficacy measures were noted (P < 0.001). CONCLUSIONS The results of this open-label study indicated that the combination of DMIQ (dose range, DM30/Q30-DM120/Q120) was well tolerated in patients with pain associated with DPN. Based on the preliminary efficacy results, a randomized, controlled, double-blind trial is warranted to assess the tolerability and efficacy of this combination in patients with DPN.
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9.
Validation of a novel screening device (NeuroQuick) for quantitative assessment of small nerve fiber dysfunction as an early feature of diabetic polyneuropathy.
Ziegler, D, Siekierka-Kleiser, E, Meyer, B, Schweers, M
Diabetes care. 2005;(5):1169-74
Abstract
OBJECTIVE To validate a handheld screening device (NeuroQuick) for an early detection of diabetic distal symmetric polyneuropathy (DSP) by quantitative testing of cold sensation based on the wind chill factor (NeuroQuick threshold [NQT]). RESEARCH DESIGN AND METHODS NQT was measured on the dorsum of the foot in 160 healthy subjects as well as 60 and 128 diabetic patients without and with DSP, respectively. DSP was diagnosed by a neurological examination, motor and sensory nerve conduction velocity, vibration perception threshold, and warm and cold thermal perception threshold (TPT) (TPT Medoc). In addition, a C-64 Hz tuning fork and TipTherm device were used as screening instruments. RESULTS In the diabetic cohort, NQT correlated significantly with all nerve function tests, with the highest correlation coefficients being found on the foot versus Medoc warm TPT (r = 0.618, P < 0.001) and cold TPT (r = 0.529, P < 0.001). Among patients with DSP, NQT was abnormal, whereas Medoc warm TPT was normal in 34%, whereas only 5% showed the opposite constellation (P < 0.05). Likewise, the corresponding percentages for Medoc cold TPT were 32 and 11%, for TipTherm 47 and 2%, and for the tuning fork 29 and 10% (all P < 0.05), whereas no significant differences were noted when comparing NQT with peroneal motor nerve conduction velocity, sural sensory nerve conduction velocity, and malleolar vibration perception threshold. The coefficients of variation for repeated NQT measurements in 41 control and 41 diabetic subjects were 20.4 and 8.5%, respectively. CONCLUSIONS The NeuroQuick is a valid and reliable screening tool for quantitative assessment of small nerve fiber dysfunction. This device appears to be more sensitive in detecting early diabetic polyneuropathy than both elaborate thermal testing and screening tests such as the tuning fork.
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10.
A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report.
Valensi, P, Le Devehat, C, Richard, JL, Farez, C, Khodabandehlou, T, Rosenbloom, RA, LeFante, C
Journal of diabetes and its complications. 2005;(5):247-53
Abstract
BACKGROUND QR-333, a topical compound that contains quercetin, a flavonoid with aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms. This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy. METHODS This randomized, placebo-controlled, double-blind trial included 34 men and women (21-71 years of age) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo (2:1 ratio), three times daily for 4 weeks, to each foot where symptoms were experienced. Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life (efficacy). Safety was assessed through concomitant medications, adverse events, laboratory evaluations, and physical examinations. RESULTS QR-333 reduced the severity of numbness, jolting pain, and irritation from baseline values. Improvements were also seen in overall and specific quality-of-life measures. QR-333 was well tolerated. Eleven patients in the QR-333 group reported 23 adverse events (all mild or moderate); 4 in the placebo group reported 5 events (all moderate). One patient who applied QR-333 noted a pricking sensation twice, the only adverse event considered possibly related to study treatment. CONCLUSIONS From this preliminary safety study, it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life. These findings warrant further investigation of this topical compound.