Cytoflavin in the Treatment of Patients With Diabetic Polyneuropathy (CYLINDER)

Inclusion Criteria:

• Signed informed consent form;
• Men and women aged 45 to 74 (inclusive);
• Confirmed diagnosis of type 2 diabetes lasting for 1 year or more;
• Permanent scheme of therapy (without changing doses and drugs) by oral hypoglycemic drugs and / or insulin, long-term or ultra-long (adjustment of insulin dose is possible within 10% from baseline dose) and / or agonists of glucagon-like peptide-1 receptors (GLP-1) for at least 12 weeks before screening;
• HbA1c from 7.0 and not higher than 10.0%;
• BMI 22-40 kg / m2;
• Symptomatic distal sensorimotor diabetic polyneuropathy;
• Baseline TSS (Total Syptom Score) ˃5 points;
• Score ≥2 by at least one of the TSS symptoms;
• The severity of pain by the corresponding TSS subscale ≤ 2;
• NISLL (Neuropathy Impairment Score Low Limbs) ≥ 2 points;
• Patient consent to use adequate contraceptive methods for the entire study;
• Consent to maintain a stable diet, exercise, therapy and diabetes control throughout the study;
• Ability to comply with all protocol requirements.

Exclusion Criteria:

• Pregnant or lactating women, or women planning a pregnancy during a clinical trial;
• Type 1 diabetes and other specific types of diabetes;
• Acute metabolic complications of diabetes such as ketoacidosis or hyperosmolar state within 6 months prior to screening;
• Therapy with short and ultra-short insulin within 3 months before screening;
• Fasting plasma glucose at screening> 15 mmol / l;
• The presence of severe complications of diabetes;
• Epilepsy, epileptiform seizures, head trauma with loss of consciousness, tumor, inflammatory and demyelinating diseases of the central nervous system;
• Diseases requiring prior or current treatment by systemic corticosteroid drugs, cytostatics or penicillamine;malignant neoplasms within the last 5 years (excluding basal cell carcinoma);
• Cardiovascular diseases in the stage of decompensation at present or within 3 months before screening;
• Uncontrolled arterial hypertension with systolic arterial pressure> 180 mm Hg and diastolic blood pressure> 110 mm Hg at screening;
• Nephrotic syndrome, severe chronic renal failure or significant kidney disease with a level of glomerular filtration rate (GFR) <30 ml / min;
• Active viral (hepatitis B and C) or cirrhotic liver disease; increased aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) 3 times from upper normal limit; increased total bilirubin 2 times from upper normal limit;
• HIV; a severe infectious disease within 30 days before screening;
• Anemia (hemoglobin ≤ 105 g / l in women or ≤ 115 g / l in men); acute blood loss or donation of at least one unit of blood (500 ml) or blood transfusion within the previous 12 weeks;
• Drug or alcohol abuse;
• Intake of Cytoflavin® for 3 months before screening;
• Known allergies, hypersensitivity or contraindications to the drug Cytoflavin® or its components;
• Intake of alpha-lipoic acid, thiamine derivatives, pyridoxine, cyanocobalamin (excluding multivitamins), antidepressants and derivatives of gabapentin within 3 months before screening;
• Use of other investigational drugs within 3 months prior to screening;
• Inability to read or write; unwillingness to understand and follow protocol procedures; non-compliance with the protocol requirements.