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Publication Efficacy and safety of trazodone and gabapentin fixed-dose combination in patients affected by painful diabetic neuropathy : randomized, controlled, dose-finding study(Springer, 2024-08) Tesfaye, Solomon; Saravanan, Ponnusamy; Ehler, Edvard; Zinek, Karel; Palka-Kisielowska, Ilona; Nastaj, Marcin; Serusclat, Pierre; Lipone, Paola; Vergallo, Andrea; Quarchioni, Elisa; Calisti, Fabrizio; Comandini, Alessandro; Cattaneo, Agnese; Sheffield Teaching Hospitals NHS Foundation Trust; George Eliot Hospital NHS Trust, Nuneaton; University of Warwick; Regional Hospital Pardubice, Czech Republic; et al.; Diabetes, Endocrinology and Metabolism; Medical and Dental; Saravanan, PonnusamyIntroduction: Up to 50% of diabetic patients with neuropathy suffer from chronic pain, namely painful diabetic neuropathy (PDN), an unmet medical need with significant impact on quality of life. Gabapentin is widely used for PDN, albeit with frequent dose-limiting effects. Trazodone, an antidepressant with multi-modal action, has shown promising results when given at low doses as an add-on to gabapentin. Upon previous clinical trials and experimental evidence, a fixed-dose combination (FDC) of both compounds, at low doses, was developed for neuropathic pain. Methods: This was a phase II, randomized, double-blind, placebo and reference controlled, dose-finding, multicenter, international, prospective study. Male and female diabetic patients aged 18-75 years and affected by PDN were eligible for enrolment. Patients were randomized (1:1:1:1:2 ratio) to trazodone and gabapentin (Trazo/Gaba) 2.5/25 mg t.i.d. for 8 weeks, Trazo/Gaba 5/50 mg t.i.d. for 8 weeks, Trazo/Gaba 10/100 mg t.i.d. for 8 weeks, gabapentin (Gaba), or placebo (PLB). The aim of the study was to collect preliminary information on the effect of the 3 different FDCs of Trazo/Gaba on pain intensity based on the 11-point numeric rating score (NRS) after 8 weeks of treatment. The secondary objectives were the evaluation of the percentage of responders, neuropathic pain symptoms, anxiety, sleep, quality of life, safety, and tolerability. The primary efficacy endpoint was evaluated with last observation carried out forward (LOCF), using an analysis of covariance (ANCOVA), including treatment and centers as factors and baseline as covariate and applying linear contrast test, excluding the active treatment. Only if the linear contrast test was significant (p < 0.05), the step-down Dunnett test would be used to determine the minimum effective dose significantly different from PLB. If linearity was not verified, an adjusted ANCOVA model and comparisons with Dunnett test were performed. Before the application of the ANCOVA model, the non-significance of interaction treatment per baseline was verified. Results: A total of 240 patients were included in the modified intention-to-treat (m-ITT) population: 39 in Trazo/Gaba 2.5/25 mg, 38 in Trazo/Gaba 5/50 mg, 37 in Trazo/Gaba 10/100 mg, 83 in PLB, and 43 in Gaba. After 8 weeks of treatment, changes of the average daily pain score based on the 11-point NRS from baseline were - 2.52 ± 2.31 in Trazo/Gaba 2.5/25 mg group, - 2.24 ± 1.96 in Trazo/Gaba 5/50 mg group, - 2.46 ± 2.12 in Trazo/Gaba 10/100 mg group, - 1.92 ± 2.21 in Gaba group, and - 2.02 ± 1.95 in the PLB group. The linear contrast test did not result in significant differences (p > 0.05) among treatment groups. Consequently, the minimum effective dose against PLB was not determined. The multiple comparison with Dunnett adjustment did not show any statistically significant differences vs. PLB after 8 weeks of treatment: Trazo/Gaba 2.5/25 mg (95% confidence interval (CI) - 1.2739, 0.2026; p = 0.1539); Trazo/Gaba 5/50 mg (95% CI - 0.9401, 0.5390; p = 0.5931); Trazo/Gaba 10/100 mg (95% CI - 1.0342, 0.4582; p = 0.4471). However, patients receiving the lowest dose of Trazo/Gaba 2.5/25 mg showed a statistically significant difference to PLB after 6 weeks of treatment (95% CI - 1.6648, - 0.2126; p = 0.0116). Positive results were also found for responder patients, other items related to the pain, anxiety, depression, sleep, and quality of life, consistently in favor to the lowest Trazo/Gaba FDC. Two serious adverse events (SAEs) occurred but were judged unrelated to the study treatment. Treatment-emergent adverse events (TEAEs) were mainly mild-to-moderate in intensity and involved primarily nervous system, gastrointestinal disorders, and investigations. Conclusions: The primary end point of the study was the change from baseline of the average daily pain score based on the 11-point NRS after 8 weeks of treatment. While the primary endpoint was not reached, patients treated with Trazo/Gaba 2.5/25 mg t.i.d. showed statistically significant improvement of pain and other scores after 6 weeks and reported consistent better results in comparison to PLB on primary and secondary endpoints for the overall study duration. According to these results, the lowest dose of Trazo/Gaba FDC may be the best candidate for further clinical development to confirm the potential benefits of the FDC drug for this condition. Clinical trial registration: NCT03749642. Keywords: Painful diabetic neuropathy; Trazodone.Publication Journal club: Type 2 diabetes – reframing the first stage of care(OmniaMed Communications, 2024-05-21) Patel, Vinod; University of Warwick; George Eliot Hospital NHS Trust; Diabetes and Endocrinology; Medical and Dental; Patel, VinodThe focus should be on remission or improvement of glycaemic control at diagnosis, but what does the evidence say is the most realistic diet?Publication All-cause mortality in type 2 diabetes : it’s all about the eGFR and not the serum creatinine(SB Communications Group, 2015-04-10) Patel, Vinod; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodA Clinical Digest piece reviewing cardiovascular journal articles.Publication A mixed bag of ideas for CVD risk reduction and finding diabetes in the vascular clinic(SB Communications Group, 2015-10-05) Patel, Vinod; University of Warwick; George Eliot Hospital, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodA Clinical Digest piece reviewing cardiovascular and major journal articles.Publication Cardiovascular outcomes trials for glucose-lowering therapies : what do the results mean for practice?(SB Communications Group, 2015-12-15) Newland-Jones, Phillip; Patel, Vinod; University of Southampton; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodDigestDEBATE: In this section, a panel of multidisciplinary team members give their opinions on a recently published paper. In this issue, we discuss the outcome of the cardiovascular safety trial of empagliflozin, and what the results mean for clinical practice in the UK.Publication Hypoglycaemia, CVD risk and mortality : a reminder of some Latin, ethical principles and patient safety(SB Communications Group, 2015-07-05) Patel, Vinod; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodA Clinical Digest piece reviewing diabetes journal articles.Publication The metabolic syndrome? Time to reconsider its clinical usefulness(SB Communications Group, 2015-12-15) Patel, Vinod; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodA Clinical Digest piece reviewing diabetes journal articles.Publication Low maternal vitamin B12 status is associated with lower cord blood HDL cholesterol in white Caucasians living in the UK(MDPI, 2015-04-02) Adaikalakoteswari, Antonysunil; Vatish, Manu; Lawson, Alexander; Wood, Catherine; Sivakumar, Kavitha; McTernan, Philip. G; Webster, Craig; Anderson, Neil; Yajnik, Chittaranjan. S; Tripathi, Gyanendra; Saravanan, Ponnusamy; University of Warwick; University of Oxford; Heartlands Hospital, Birmingham; George Eliot Hospital NHS Trust, Nuneaton; University Hospitals Coventry and Warwickshire NHS Trust; Diabetes and Endocrinology; Medical and Dental; Wood, Catherine; Anderson, Neil; Saravanan, PonnusamyBackground and aims: Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth. Methods: This is a cross-sectional study of 91 mother-infant pairs (n = 182), of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood). Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured. Results: The prevalence of low serum vitamin B12 (<191 ng/L) and folate (<4.6 μg/L) were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring's Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR), triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR. Conclusions: Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol.Publication Xultophy : combination therapy for the treatment of type 2 diabetes(Wiley, 2015-09-04) Chaplin, Steve; Patel, Vinod; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodXultophy is the first product to combine a basal insulin and an incretin mimetic for the treatment of type 2 diabetes. Here Steve Chaplin presents the clinical data relating to its efficacy and adverse events and Vinod Patel outlines its place in therapy.Publication Type 2 diabetes : pharmacological management strategies(Pharmaceutical Press, 2015-11) Packer, Mary E.; Crasto, Winston; George Eliot Hospital NHS Trust; Diabetes and Endocrinology; Medical and Dental; Packer, Mary E.; Crasto, WinstonCurrent and future treatment options for the management of patients with type 2 diabetes. In this article you will learn: The current pharmacological strategies for management of patients with type 2 diabetes The status of newer therapies targeting the incretin axis and renal glucose handling The status of newer, longer-acting insulinsPublication The outcome of dapagliflozin use in a real-life clinical setting in multi-district general hospitals(Wiley, 2015-03-11) Bellan Kannan, R.; Othonos, N.; Dimitriadis, G.; Barber, T.; Murthy, N.; Young, J.; Saravanan, P.; Mahto, R.; Raja, U.; South Warwickshire University NHS Foundation Trust; George Eliot Hospital NHS Trust, Nuneaton; University Hospitals Coventry and Warwickshire NHS Trust; Worcestershire Acute Hospitals NHS Trust; Diabetes and Endocrinology; Medical and Dental; Othonos, N.; Saravanan, P.Poster abstract P470 in the section 'Clinical care and other categories posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Low breastfeeding rates in women with high risk of gestational diabetes : differences between South Asians and Caucasians(Wiley, 2015-03-11) Vekaria, R.; Bhatt, R.; Venkataraman, H.; Sukumar, N.; Saravanan, P.; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Saravanan, P.Poster abstract P493 in the section 'Clinical care and other categories posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication An audit looking at general practitioner (GP) referrals of adult patients with diabetes undergoing surgery(Wiley, 2015-03-11) Thorp, V.; Owen, S.; Nair, R.; Cosh, H.; Povey, M.; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Thorp, V.; Owen, S.; Nair, R.; Cosh, H.; Povey, M.Poster abstract P258 in the section 'Clinical care and other categories posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Predictors of prematurity in metformin-treated gestational diabetes (GDM)(Wiley, 2015-03-11) Khin, M. O.; Gates, S.; Saravanan, P.; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Saravanan, P.Poster abstract P498 in the section 'Clinical care and other categories posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Maternal homocysteine levels at the time of diagnosis independently predict small-for-gestational-age (SGA) infants in gestational diabetes (GDM)(Wiley, 2015-03-11) Khin, M. O.; Wilson, S. D.; Gates, S.; Saravanan, P.; University of Warwick; University of Hull; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Saravanan, P.Poster abstract P495 in the section 'Clinical care and other categories posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Effects of maternal diabetes and body mass index (BMI) on offspring birth weight vary across ethnic groups(Wiley, 2015-03-11) Venkataraman, H.; Wilson, J.; Seaton, S.; Sukumar, N.; Khunti, K.; Saravanan, P.; University of Warwick; University College London Hospitals NHS Foundation Trust; University of Leicester; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Saravanan, P.Poster abstract P164 in the section 'Basic and clinical science posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Antenatal customised growth charts overestimate offspring birth weight in gestational diabetes(Wiley, 2015-03-11) Johnson, J.; Mundell, C.; Sukumar, N.; Venkataraman, H.; Saravanan, P.; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Sukumar, N.; Venkataraman, H.; Saravanan, P.Poster abstract P162 in the section 'Basic and clinical science posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Early ethnic differences in fetal growth patterns in gestational diabetes (GDM)(Wiley, 2015-03-11) Venkataraman, H.; Craik, S.; Midgley, E.; Sukumar, N.; Ram, U.; Saravanan, P.; University of Warwick; Seethapathy-Mediscan, Chennai, India; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Saravanan, P.Poster abstract P161 in the section 'Basic and clinical science posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Low vitamin B12 in pregnancy is associated with maternal obesity and gestational diabetes(Wiley, 2015-03-11) Sukumar, N.; Wilson, S.; Venkataraman, H.; Saravanan, P.; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Sukumar, N.; Wilson, S.; Venkataraman, H.; Saravanan, P.Poster abstract P159 in the section 'Basic and clinical science posters' of the Diabetes UK Professional Conference 2015, ExCeL London, 11–13 March 2015.Publication Time to stress those new year’s resolutions again!(SB Communications Group, 2016-04-11) Patel, Vinod; University of Warwick; George Eliot Hospital NHS Trust, Nuneaton; Diabetes and Endocrinology; Medical and Dental; Patel, VinodA Clinical Digest piece reviewing cardiovascular and major journal articles.