Diabetic NeuropathiesPhase 3CYLINDERNCT04649203
Cytoflavin in the Treatment of Patients With Diabetic Polyneuropathy
A Phase 3 study testing Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid) in people with Diabetic Neuropathies, run by POLYSAN Scientific & Technological Pharmaceutical Company at 16 sites in Russia.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 74 years
- Conditions the study is for
- Diabetic Neuropathies
- What is being tested?
- Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 216 participants
- Where
- 16 sitesRussia
- Study dates
- 25 Nov 2020to 6 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Russia16 sites
City Clinical Hospital n.a. V.P.Demikhov
Moscow
City Clinical Hospital n.a.M.E.Zhadkevitch
Moscow
City Clinical Hospital #13 Avtozavodsky district
Nizhny Novgorod
Research Center for Eco-safety, Ltd.
Saint Petersburg, 196143
"Astarta" Ltd.
Saint Petersburg
"Consultative and diagnostic center with a polyclinic" of the Administrative Department of the President of the Russian Federation
Saint Petersburg
Almazov National Medical Research Centre
Saint Petersburg
City General Hospital №2
Saint Petersburg
City Outpatient Clinic #117
Saint Petersburg
City Outpatient Clinic #51
Saint Petersburg
I. P. Pavlov 1st St. Petersburg State Medical University
Saint Petersburg
MEDICA Ltd.
Saint Petersburg
North-West State Medical University named after I.I. Mechnikov
Saint Petersburg
"Diabetes" medical center
Samara
Saratov State Medical University n.a. V.I.Razumovsky
Saratov
GBUZ YAO "Regional Clinical Hospital"
Yaroslavl
About this study
Official title: Multicenter, Double-blind, Placebo-controlled Randomized Clinical Trial of Efficacy and Safety of the Drug Cytoflavin®, Administered Intravenously Followed by Oral Intake, in Patients With Diabetic Polyneuropathy
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
- Being tested
- Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid), Placebo
- Keywords
- Diabetes Mellitus, Peripheral Nervous System Diseases, Antioxidants, Succinic acid
- Medical subject headings
- Diabetic Neuropathies, Diabetes Mellitus, Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
TSS (Total Symptom Score)
Change in total TSS score at Week 12 from baseline
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2020
- Study start25 Nov 2020
- Primary completion29 Mar 2021
- Study completion6 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic NeuropathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 216 participants (actual)
Sponsor and investigators
- Lead sponsor
- POLYSAN Scientific & Technological Pharmaceutical Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Igor A Strokov, Prof., Study chair, "First Moscow State Medical University n.a. I.M.Sechenov of the Ministry of Health of Russia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04649203
- Sponsor's protocol ID
- CTF-III-DM-2019
- Acronym
- CYLINDER
- Status last verified
- Jan 2023
- First submitted
- 24 Nov 2020
- Last updated
- 27 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 35680173
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Double-blind, Placebo-controlled Randomized Clinical Trial of Efficacy and Safety of the Drug Cytoflavin®, Administered Intravenously Followed by Oral Intake, in Patients With Diabetic Polyneuropathy
- ClinicalTrials.gov ID
- NCT04649203
- Acronym / sponsor ID
- CYLINDER / CTF-III-DM-2019
- Conditions
- Diabetic Neuropathies
- Keywords
- Diabetes Mellitus, Peripheral Nervous System Diseases, Antioxidants, Succinic acid
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 216 participants (actual)
- Lead sponsor
- POLYSAN Scientific & Technological Pharmaceutical CompanyIndustry (pharma, biotech, devices)
- Study start
- 25 Nov 2020 (actual)
- Primary completion
- 29 Mar 2021 (actual)
- Study completion
- 6 Jun 2021 (actual)
- First posted
- 2 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid)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 |
| Group 2 | Placebo comparator | Drug: PlaceboPlacebo, 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 |
Who may qualify
- Ages
- 45 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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%;
Key exclusion criteria (20 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid)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. | Drug | Group 1 |
| PlaceboThe 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. | Drug | Group 2 |
Primary outcome
TSS (Total Symptom Score)
Time frame: 12 weeks
Change in total TSS score at Week 12 from baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2023.
- Results publication: PubMed 35680173Kharitonova 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Igor A Strokov, Prof. study chair
"First Moscow State Medical University n.a. I.M.Sechenov of the Ministry of Health of Russia
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cytoflavin (Inosine + Nicotinamide + Riboflavin + Succinic Acid) in people with Diabetic Neuropathies, run by POLYSAN Scientific & Technological Pharmaceutical Company at 16 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TSS (Total Symptom Score) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04649203, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2023.