Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type I Diabetes Mellitus
|ClinicalTrials.gov Identifier: NCT01868594|
Recruitment Status : Completed
First Posted : June 4, 2013
Results First Posted : March 4, 2019
Last Update Posted : May 30, 2019
The purpose of this study is:
- to assess clinical efficacy of Subetta in the combined treatment of type I diabetes mellitus;
- to assess safety of Subetta in the combined treatment of type I diabetes mellitus.
|Condition or disease||Intervention/treatment||Phase|
|Type I Diabetes Mellitus||Drug: Subetta Drug: Placebo||Phase 4|
Patients with type I diabetes mellitus are included in the trial. It is concerned those patients, who by the time of the trial receive basal bolus insulin therapy of type I diabetes mellitus, including basal insulin (using long acting medications) and prandial insulin (short and ultra short acting medications), and with poor glycemic control (HbA1c=7.0-10.0%). For patients, which will be included in the trial (mainly middle aged patients without severe complications of diabetes), HbA1c>7.0% is the marker showing that optimal individual goal of glycemic control is not achieved.
HbA1c, fasting plasma glucose, microalbuminuria, estimated glomerular filtration rate, ophthalmoscopy, blood pressure measurement, patient self-monitoring of blood glucose, frequency of hypoglycemia, endocrinologist examination were performed within screening period. Patients without severe diabetes complications are randomized in 2 groups.
If a patient meets inclusion criteria and does not show exclusion criteria he/she is randomized in one of 2 groups: Group 1 - patients receiving standard type I diabetes mellitus therapy + Subetta at a dose of 1 tablet 4 times a day; Group 2 - the group receiving standard type I diabetes mellitus therapy + Placebo under the regimen used for Subetta. The invented names of the drugs containing basal and prandial (meal) insulin should be unchanged for each patient during the whole trial.
All patients will receive glucometers and the appropriate glucose test strips, so they could self monitor blood glucose and register this data in their diaries.
The trial duration is 38 weeks; the main stages of the trial are conducted during screening, then in 4 weeks (Visit 2), in 12 weeks (Visit 3), in 24 weeks (Visit 4) and in 36 weeks (Visit 5). In 1 week after randomization and the onset of the trial therapy and between the visits to the study site (on weeks 8±1, 18±1 and 30±1) an investigator collects data on patient's health and complaints (phone visits) to decide whether it is necessary to arrange unplanned visit to the site.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Supportive Care|
|Official Title:||Multicentre Double-blind Placebo-controlled Parallel-group Randomized Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type I Diabetes Mellitus|
|Actual Study Start Date :||May 7, 2013|
|Actual Primary Completion Date :||July 2016|
|Actual Study Completion Date :||July 10, 2016|
Experimental: Subetta group
Patients with poor glycemic control (HbA1c=7.0-10.0%) in basal-bolus insulin regimen with a stable basal insulin dose (permissible fluctuations are ±10%) during the previous 3 months are included
Each Subetta tablet contains a mixture of affinity purified polyclonal antibodies to β-subunit of the rINS (6 mg) and antibodies to eNOS (6 mg) in released-active form produced by the patented technology in accordance with the applicable European Pharmacopeia requirements.
Standard therapy of type I diabetes mellitus + Subetta (1 tablet 4 times a day) for 36 weeks.
Subetta: oral administration, per 1 intake - 1 tablet (keep in the mouth until complete dissolution, not at mealtime).
Placebo Comparator: Placebo group
Patients with poor glycemic control (HbA1c=7.0-10.0%) in basal-bolus insulin regimen with a stable basal insulin dose (permissible fluctuations are ±10%) during the previous 3 months are included.
Placebo (identical to Subetta in shape and taste tablet containing exсipients). Standard therapy of type I diabetes mellitus + Placebo (1 tablet 4 times a day) for 36 weeks.
Placebo: oral administration, per 1 intake - 1 tablet (keep in the mouth until complete dissolution, not at mealtime).
- Changes in the Mean Value of HbA1c [ Time Frame: baseline and 12, 24 and 36 weeks of the treatment ]The HbA1C test was performed using a method that is certified by the National Glycohemoglobin Standardization Program (NGSP) (www.ngsp.org) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay.
- Change in Fasting Plasma Glucose (Based on the Data of Biochemical Analysis) [ Time Frame: baseline and 4, 12, 24 and 36 weeks of the treatment ]
- Change in Average Daily Blood Glucose From a 7-point Patient Self-monitoring of Blood Glucose (SMBG) [ Time Frame: baseline and 4, 8, 12, 18, 24, 30 and 36 weeks of the treatment ]
A 7-point patient self-monitoring of blood glucose (SMBG):
three measurements of blood glucose before the meal; three measurements of postprandial blood glucose (1-2 h after the start of the meal) and one measurement at 3:00 a.m.
- Changes in Lipids (Concentrations of Plasma Total Cholesterol, HDL Cholesterol, LDL Cholesterol and Triglycerides) [ Time Frame: baseline and 12, 24 and 36 weeks of the treatment ]Blood samples (for measurement of fasting plasma glucose, concentrations of plasma total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides) are taken under standard conditions: after night break in food taking (at least 12 hours) and prior to administering of insulin morning dose (prandial), prior to any morning medicines intake (including the study drug and permitted concomitant therapy).
- Changes in Dosage of Insulin (Basal, Prandial and Total Daily Dose Insulin Measured in IU) [ Time Frame: baseline and 36 weeks of the treatment ]Insulin dose should be corrected by a patient on a daily basis taking into consideration data on blood glucose self- monitoring during a day and amount of food carbohydrates. Physician can correct insulin dose based on the same data.
- Changes in Dosage of Total Insulin Measured in IU/kg of Body Weight [ Time Frame: baseline and 36 weeks of the treatment ]Insulin dose should be corrected by a patient on a daily basis taking into consideration data on blood glucose self- monitoring during a day and amount of food carbohydrates. Physician can correct insulin dose based on the same data.
- Satisfaction of Diabetes Treatment Based on Diabetes Treatment Satisfaction Questionnaire Data [ Time Frame: 36 weeks of the treatment ]
The Diabetes Treatment Satisfaction Questionnaire allows to assess the degree of satisfaction with treatment for diabetes and its complications - retinopathy and nephropathy, how patients' satisfaction and perceived hyper- and hypoglycemia have changed compared to the initial period (before the treatment).
The Diabetes Treatment Satisfaction Questionnaire contains six items scored on 7-point scales from +3 (equals "very satisfied") to -3 (equals "very dissatisfied"), with 0 (equals "no change"). These are summed to produce a total Treatment Satisfaction score. Two questions concerning "Perceived Hyperglycaemia" and "Perceived Hypoglycaemia" respectively, are calculated separately. According to these two items, low scores represent good perceived blood glucose control (+3 means "most of the time" of Hyperglycaemia or Hypoglycaemia whereas -3 means "none of the time" of Hyperglycaemia or Hypoglycaemia).
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01868594
|Municipal budgetary authority "Khimki Central Clinical Hospital"|
|Moscow region, Russian Federation, 141400|
|State Healthcare Institution of Moscow "Central research institute of gastroenterology" of Department of health care of Moscow|
|Moscow, Russian Federation, 111123|
|State Educational Institution of Higher Professional Education "Moscow State Medical Academy named after I.M. Sechenov"|
|Moscow, Russian Federation, 119991|
|Nonstate Health Care Institution "Central Clinical Hospital №2 named after N.A. Semashko of Public Limited Company "Russian Railways"|
|Moscow, Russian Federation, 129128|
|The State Budgetary Institution of Health Care of the Nizhny Novgorod Region "City clinical hospital No. 10 "|
|Nizhny Novgorod, Russian Federation, 603011|
|Nizhny Novgorod regional State Budgetary Health Institution " Nizhny Novgorod regional Clinical Hospital named after N.A. Semashko "|
|Nizhny Novgorod, Russian Federation, 603126|
|State Budgetary Educational Institution of High Professional Training "Rostov State Medical University" of Ministry of Health of Russian Federation, Department of Endocrinology|
|Rostov-on-Don, Russian Federation, 344022|
|Co.Ltd " Diabet Center"|
|Samara, Russian Federation, 443067|
|Private company "Polyclinic Complex"|
|St. Petersburg, Russian Federation, 190013|
|St. Petersburg State Budgetary Health Care Institution "City Polyclinic №6"|
|St. Petersburg, Russian Federation, 191482|
|St. Petersburg State Budgetary Health Care Institution "Saint Venerable Martyr Elizaveta Municipal Hospital"|
|St. Petersburg, Russian Federation, 195257|
|State Budgetary Educational Institution of High Professional Training "St. Petersburg State Medical University named after academician I.P. Pavlov" of Ministry of Health of Russian Federation, Therapy Faculty Board|
|St. Petersburg, Russian Federation, 197022|
|St. Petersburg Sate Budgetary Institution "Consultative-Diagnostic Polyclinic №1 of Coastal Area"|
|St. Petersburg, Russian Federation, 197183|
|Independent Health Care Institution of Voronezh Region "Voronezh Regional Clinical Consultative-Diagnostic Center"|
|Voronezh, Russian Federation, 394018|
|State Budgetary Health Care Institution of Yaroslavl Region "Regional Сlinical Hospital"|
|Yaroslavl, Russian Federation, 150062|