Impaired Glucose Tolerance
Conditions
Brief summary
Purpose of the study: * to assess the efficacy of Subetta in the treatment of impaired glucose tolerance * to assess the safety of Subetta in the treatment of impaired glucose tolerance.
Detailed description
Design: a multicenter, double-blind, placebo-controlled, parallel-group randomized trial. The study will enroll outpatients adults aged 18 to 70 years with impaired glucose tolerance (IGT) who did not receive glucose-lowering agents previously. Persons with pre-diabetes, obesity (especially with visceral or abdominal obesity), dyslipidemia (with high triglycerides and/or low-density lipoproteins), hypertension, diabetes in first-degree relatives will be considered as potential candidates to participate in the study. After the patient's information sheet and the form of informed consent for participation in the study are signed on the screening (visit 0; day from -7 to 0), complaints and history are collected, registration of concomitant conditions and diseases, objective examination, calculation of body mass index (BMI), oral glucose tolerance test (OGTT), fasting blood glucose. Furthermore, blood samples (for testing HbA1c, chemistry and hematology, HLA genotyping) and urine sample will be collected; concomitant therapy will be recorded, diet and physical activity recommendations will be given. All women of childbearing potential will be administered pregnancy tests. If eligibility criteria are met and there are no non-inclusion criteria on Visit 1 (Day 1), the patient is randomized to one of two groups: the Subetta group (patients will take 2 tablets twice a day for 12 weeks) or placebo group (patients will take a placebo according to the scheme of Subetta for 12 weeks). In the course of the study, two more visits in 4 (Visit 2) and 12 (Visit 3) weeks are planned, during these weeks complaints are recorded, a patient's examination is recorded, therapy compliance and safety are assessed. On Visit 3 OGTT, fasting blood glucose, blood samples (for HbA1c, chemistry and hematology) and urinalysis will be performed. The duration of observation period shall be up to 13 weeks. During the study the treatment for underlying conditions will be allowed with the exception of the drugs indicated in the section Prohibited concomitant therapy.
Interventions
DRUGSubetta
Oral administration.
DRUGPlacebo
Oral administration.
Sponsors
Materia Medica Holding
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Outpatients aged 18 to 70 years. 2. Impaired glucose tolerance (plasma glucose from 7.8 to 11.0 mmol / L 2 hours after a 75 g oral glucose consumption during an oral glucose tolerance test, while fasting plasma glucose \<7.0 mmol / L). 3. HbA1c is 5.7-6.4%. 4. The body mass index is 25.0-39.9 kg / m\^2. 5. Consent to use reliable contraceptive methods during the study (for men and women with reproductive potential). 6. The presence of the signed informed consent form to participate in the clinical trial.
Exclusion criteria
1. Type 1 or type 2 diabetes. 2. Use of any medications indicated in the section Prohibited concomitant medications. 3. Acute or exacerbation / decompensation of a chronic disease of any etiology at the time of the examination or during the previous week. 4. Uncontrolled arterial hypertension with blood pressure: systolic blood pressure \> 160 mm Hg and/or diastolic blood pressure \> 110 mm Hg. 5. Acute coronary syndrome, myocardial infarction, acute impairment of cerebral circulation during the previous 6 months prior to enrollment. 6. Unstable or life-threatening arrhythmia during the previous 3 months prior to enrollment. 7. Acute and chronic heart failure with functional class III or IV (according to the classification of the New York Heart Association, 1964). 8. Respiratory failure. 9. Chronic kidney disease (classes C3-5 A3). 10. Hepatic insufficiency (class C according to Child-Pugh). 11. Presence or suspicion of oncology disease. 12. The presence of an allergy / hypersensitivity to any component of the medication administered during the treatment. 13. Alcohol consumption \> 2 alcohol units for males and \> 1 alcohol unit for females per day. 14. Mental illness or drug abuse in anamnesis. 15. Bariatric surgery in anamnesis, any surgery for 3 months before enrollment. 16. Pregnancy, breast-feeding; childbirth less than 3 months before enrollment. 17. Participation in other clinical trials for 3 months before enrollment in this study. 18. Patients who are related to any of the on-site research personnel directly involved in the conduct of the trial or are an immediate relative of the study investigator. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted). 19. Patients who work for MATERIA MEDICA HOLDING (i.e. the company's employees, temporary contract workers, appointed officials responsible for carrying out the research or immediate relatives of the aforementioned).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | At baseline and after 12 weeks of treatment. | Based on medical records. For oral glucose tolerance test, the subject is given 75 g of oral glucose and blood sample is taken 2 hours later. All analysis will be done in a central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With 2-hour Plasma Glucose <7.8 mmol / L. | After 12 weeks of treatment. | Based on medical records. |
| Change in Fasting Plasma Glucose. | At baseline and after 12 weeks of treatment. | Based on medical records. Fasting plasma glucose is measured after fasting or not eating anything for at least 8 hours. |
| Change in HbA1c | At baseline and after 12 weeks of treatment. | Based on medical records. HbA1c is determined by the method certified in accordance with National Glycohemoglobin Standardization Program and standardized in compliance with the reference values adopted in the Diabetes Control and Complications Trial. |
Countries
Russia
Participant flow
Pre-assignment details
After screening procedures 336 patients were excluded by the researchers because they did not meet the inclusion criteria, or they had non-inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Subetta Oral administration. 2 tablets 2 times a day 15 minutes before meals. Keep the tablets in your mouth, not swallowing, until completely they are dissolved.
Subetta: For oral use. | 105 |
| Placebo Oral administration. 2 tablets 2 times a day 15 minutes before meals. Keep the tablets in your mouth, not swallowing, until completely they are dissolved.
Placebo: For oral use. | 97 |
| Total | 202 |
Baseline characteristics
| Characteristic | Placebo | Total | Subetta |
|---|---|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 8.6 | 56.4 years STANDARD_DEVIATION 9 | 56.6 years STANDARD_DEVIATION 9.3 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Russia | 97 participants | 202 participants | 105 participants |
| Sex: Female, Male Female | 75 Participants | 153 Participants | 78 Participants |
| Sex: Female, Male Male | 22 Participants | 49 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 97 |
| other Total, other adverse events | 15 / 105 | 20 / 97 |
| serious Total, serious adverse events | 0 / 105 | 0 / 97 |
Outcome results
Primary
Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test).
Based on medical records. For oral glucose tolerance test, the subject is given 75 g of oral glucose and blood sample is taken 2 hours later. All analysis will be done in a central laboratory.
Time frame: At baseline and after 12 weeks of treatment.
Population: 9 randomized patients who received full treatment and underwent all procedures according to the protocol (n = 4, Subetta group; n = 5, Placebo group) were excluded from analysis. Blood samples were obtained but the central laboratory did not provide carbohydrate metabolism values due to technical reasons for these patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subetta | Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | Baseline | 9.27 mmol/L | Standard Deviation 0.88 |
| Subetta | Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | After 12 weeks | 7.28 mmol/L | Standard Deviation 2.07 |
| Subetta | Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | ∆ between baseline and after 12 weeks | -1.99 mmol/L | Standard Deviation 2.21 |
| Placebo | Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | Baseline | 9.11 mmol/L | Standard Deviation 0.86 |
| Placebo | Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | After 12 weeks | 8.32 mmol/L | Standard Deviation 2.44 |
| Placebo | Change 2-hour Plasma Glucose (During Oral Glucose Tolerance Test). | ∆ between baseline and after 12 weeks | -0.79 mmol/L | Standard Deviation 2.55 |
Comparison: This analysis applies to ∆ between baseline and after 12 weeks row.p-value: 0.0028Wilcoxon (Mann-Whitney)
Secondary
Change in Fasting Plasma Glucose.
Based on medical records. Fasting plasma glucose is measured after fasting or not eating anything for at least 8 hours.
Time frame: At baseline and after 12 weeks of treatment.
Population: 9 randomized patients who received full treatment and underwent all procedures according to the protocol (n = 4, Subetta group; n = 5, Placebo group) were excluded from analysis. Blood samples were obtained but the central laboratory did not provide carbohydrate metabolism values due to technical reasons for these patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subetta | Change in Fasting Plasma Glucose. | Baseline | 5.83 mmol/L | Standard Deviation 0.62 |
| Subetta | Change in Fasting Plasma Glucose. | After 12 weeks | 6.01 mmol/L | Standard Deviation 1.17 |
| Subetta | Change in Fasting Plasma Glucose. | ∆ between baseline and after 12 weeks | 0.18 mmol/L | Standard Deviation 1.25 |
| Placebo | Change in Fasting Plasma Glucose. | Baseline | 5.88 mmol/L | Standard Deviation 0.6 |
| Placebo | Change in Fasting Plasma Glucose. | After 12 weeks | 6.02 mmol/L | Standard Deviation 0.92 |
| Placebo | Change in Fasting Plasma Glucose. | ∆ between baseline and after 12 weeks | 0.14 mmol/L | Standard Deviation 1.06 |
Comparison: This analysis applies to ∆ between baseline and after 12 weeks row.p-value: 0.99Wilcoxon (Mann-Whitney)
Secondary
Change in HbA1c
Based on medical records. HbA1c is determined by the method certified in accordance with National Glycohemoglobin Standardization Program and standardized in compliance with the reference values adopted in the Diabetes Control and Complications Trial.
Time frame: At baseline and after 12 weeks of treatment.
Population: 9 randomized patients who received full treatment and underwent all procedures according to the protocol (n = 4, Subetta group; n = 5, Placebo group) were excluded from analysis. Blood samples were obtained but the central laboratory did not provide carbohydrate metabolism values due to technical reasons for these patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Subetta | Change in HbA1c | Baseline | 5.9 percentage of HbA1c |
| Subetta | Change in HbA1c | After 12 weeks | 5.8 percentage of HbA1c |
| Subetta | Change in HbA1c | ∆ between baseline and after 12 weeks | -0.1 percentage of HbA1c |
| Placebo | Change in HbA1c | Baseline | 6.0 percentage of HbA1c |
| Placebo | Change in HbA1c | After 12 weeks | 5.9 percentage of HbA1c |
| Placebo | Change in HbA1c | ∆ between baseline and after 12 weeks | -0.1 percentage of HbA1c |
Comparison: This analysis applies to ∆ between baseline and after 12 weeks row.p-value: 0.79Wilcoxon (Mann-Whitney)
Secondary
Percentage of Patients With 2-hour Plasma Glucose <7.8 mmol / L.
Based on medical records.
Time frame: After 12 weeks of treatment.
Population: 9 randomized patients who received full treatment and underwent all procedures according to the protocol (n = 4, Subetta group; n = 5, Placebo group) were excluded from analysis. Blood samples were obtained but the central laboratory did not provide carbohydrate metabolism values due to technical reasons for these patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subetta | Percentage of Patients With 2-hour Plasma Glucose <7.8 mmol / L. | 64 Participants |
| Placebo | Percentage of Patients With 2-hour Plasma Glucose <7.8 mmol / L. | 46 Participants |
p-value: 0.0805Fisher Exact