RT Journal Article
SR Electronic
T1 Efficacy and safety of the combined metabolic medication, containing inosine, nicotinamide, riboflavin and succinic acid, for the treatment of diabetic neuropathy: a multicenter randomized, double-blind, placebo-controlled parallel group clinical trial (CYLINDER)
JF BMJ Open Diabetes Research & Care
JO BMJ Open Diab Res Care
FD American Diabetes Association
SP e002785
DO 10.1136/bmjdrc-2022-002785
VO 10
IS 3
A1 Tatiana Kharitonova
A1 Yury G Shvarts
A1 Andrey F Verbovoy
A1 Natalia S Orlova
A1 Valentina P Puzyreva
A1 Igor A Strokov
YR 2022
UL http://drc.bmj.com/content/10/3/e002785.abstract
AB Introduction Antioxidants may have positive impact on diabetic polyneuropathy (DPN), presumably due to alleviation of oxidative stress. We aimed to evaluate the efficacy and safety of combination of antioxidants: succinic acid, inosine, nicotinamide, and riboflavin (SINR) in the treatment of DPN.Research design and methods In a double-blind, placebo-controlled clinical trial, men and women aged 45–74 years with type 2 diabetes and symptomatic DPN, with initial Total Symptom Score (TSS) ˃5, were randomized into experimental (n=109) or placebo (n=107) group. Patients received study medication/placebo intravenously for 10 days, followed by oral administration for 75 days. Statistical significance was defined as a two-tailed p<0.05.Results In SINR group, mean TSS change after 12 weeks was –2.65 (±1.46) vs –1.73 (±1.51) in the placebo group (p<0.0001; t-test). Reduction of symptoms in the SINR group was achieved regardless of hemoglobin A1c levels, but better results were observed in patients with initial TSS <7.5. The analysis of TSS subscores revealed statistically significant between-group differences by dynamics of the intensity of paresthesia and of numbness starting from day 11 (p=0.035 and p=0.001, respectively; mixed model); by day 57, statistically significant between-group differences were detected also by dynamics of burning intensity (p=0.005; mixed model). Study limitations are small effect size, moderate proportion of patients with severe DPN symptoms, subjective assessment of outcomes, exclusion of participants who received injectable glucose-lowering medications other than insulins, and patients with uncontrolled and type 1 diabetes.Conclusions The combination of SINR effectively alleviates DPN symptoms in patients with type 2 diabetes.Trial registration number ClinicalTrials.gov Registry (NCT04649203; Unique Protocol ID: CTF-III-DM-2019).Data may be obtained from a third party and are not publicly available. Data were collected and stored by an independent CRO.