Cytoflavin in the Treatment of Patients With Diabetic Polyneuropathy

NCT04649203 | Completed Phase 3

• 1 other identifier: CTF-III-DM-2019
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 16

Brief Summary

One of the most common complications of diabetes mellitus is diabetic polyneuropathy, which leads to disability and reduces quality of life. The toxic effects of high glucose concentrations contribute to the formation of ketoaldehyde free radicals, which, at an increased rate of their formation, leads to the development of oxidative stress in the nervous tissue. The planned study of the use of Cytoflavin® in diabetic polyneuropathy is substantiated by its antioxidant effect, which, by analogy with alpha-lipoic acid preparations, suggests its efficacy in the combined treatment of such patients. This clinical study is being conducted to assess the efficacy and safety of Cytoflavin® versus Placebo in diabetic polyneuropathy patients with type 2 diabetes. Study patients will receive study medication, 10 IV infusions followed by 75 days of oral intake. Clinical efficacy will be assessed by alleviation of symptoms (burning, numbness, pain and pricking), using the total symptoms score(TSS), after the completion of the treatment course.

Conditions

Diabetic Neuropathies

Keywords

Diabetes Mellitus; Peripheral Nervous System Diseases; Antioxidants; Succinic acid

Outcome Measures

Primary Outcomes (1)

• TSS (Total Symptom Score)

  Change in total TSS score at Week 12 from baseline

  12 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid), 20 ml (two ampoules of 10 ml each) once a day intravenously in a dilution of 200 ml of 0.9% sodium chloride solution at a rate 3-4 ml/min, for 10 days + Cytoflavin ((Inosine + Nicotinamide + Riboflavin + Succinic Acid), 2 tablets 2 times a day, for 75 days

Drug: Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid)

Group 2

PLACEBO COMPARATOR

Placebo, 20 ml (two ampoules of 10 ml each) once a day intravenously in a dilution of 200 ml of 0.9% sodium chloride solution at a rate 3-4 ml / min, for 10 days + Placebo, 2 tablets 2 times a day, for 75 days

Drug: Placebo

Interventions

Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid) DRUG

The study drug will be administered in two phases: intravenous infusion of study drug for 10 days followed by oral administration of study drug for 75 days. Thus, the total duration of the study therapy is 12 weeks.

Group 1

Placebo DRUG

The placebo comparator will be administered in two phases: intravenous infusion of placebo solution for 10 days followed by oral administration of placebo pills for 75 days. Thus, the total duration of the study therapy is 12 weeks.

Group 2

Eligibility Criteria

• Age: 45 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• POLYSAN Scientific & Technological Pharmaceutical Company: lead

Study Sites (16)

City Clinical Hospital n.a. V.P.Demikhov

Moscow, Russia

Location

City Clinical Hospital n.a.M.E.Zhadkevitch

Moscow, Russia

Location

City Clinical Hospital #13 Avtozavodsky district

Nizhny Novgorod, Russia

Location

Research Center for Eco-safety, Ltd.

Saint Petersburg, 196143, Russia

Location

"Astarta" Ltd.

Saint Petersburg, Russia

Location

"Consultative and diagnostic center with a polyclinic" of the Administrative Department of the President of the Russian Federation

Saint Petersburg, Russia

Location

Almazov National Medical Research Centre

Saint Petersburg, Russia

Location

City General Hospital №2

Saint Petersburg, Russia

Location

City Outpatient Clinic #117

Saint Petersburg, Russia

Location

City Outpatient Clinic #51

Saint Petersburg, Russia

Location

I. P. Pavlov 1st St. Petersburg State Medical University

Saint Petersburg, Russia

Location

MEDICA Ltd.

Saint Petersburg, Russia

Location

North-West State Medical University named after I.I. Mechnikov

Saint Petersburg, Russia

Location

"Diabetes" medical center

Samara, Russia

Location

Saratov State Medical University n.a. V.I.Razumovsky

Saratov, Russia

Location

GBUZ YAO "Regional Clinical Hospital"

Yaroslavl, Russia

Location

Related Publications (1)

• Kharitonova T, Shvarts YG, Verbovoy AF, Orlova NS, Puzyreva VP, Strokov IA. 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). BMJ Open Diabetes Res Care. 2022 Jun;10(3):e002785. doi: 10.1136/bmjdrc-2022-002785.

  PMID: 35680173 RESULT

MeSH Terms

Conditions

Diabetic Neuropathies; Diabetes Mellitus; Peripheral Nervous System Diseases

Interventions

cytoflavin; Inosine; Niacinamide; Riboflavin; Succinic Acid

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Flavins; Pteridines; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors; Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Igor A Strokov, Prof.

  "First Moscow State Medical University n.a. I.M.Sechenov of the Ministry of Health of Russia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 2, 2020
• Study Start: November 25, 2020
• Primary Completion: March 29, 2021
• Study Completion: June 6, 2021
• Last Updated: January 27, 2023

Record last verified: 2023-01

Locations

RU (16)