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Clinical Trial of Efficacy and Safety of Subetta in the Combined Treatment of Patients With Type I Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01868594
Recruitment Status : Completed
First Posted : June 4, 2013
Results First Posted : March 4, 2019
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
Materia Medica Holding

Brief Summary:

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

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
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
Drug: Subetta

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.
Drug: Placebo

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).





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]
  2. 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.


  3. 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).

  4. 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.

  5. 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.

  6. 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).




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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosed type I diabetes mellitus (according to WHO criteria, 1999 - 2006).
  2. Disease duration no less than 6 months.
  3. Patient's age from 18 to 65 years inclusive.
  4. Level of glycosylated hemoglobin 7.0- 10.0 %.
  5. Glomerular filtration rate ≥ 60 ml/ min/1.73m^2.
  6. Stable dose of basal insulin for the last 3 months. (Permissible fluctuations are ±10%.)
  7. Usage of contraceptive methods by both gender patients of reproductive age during the trial and within 30 days after ending the participation in the trial.
  8. Availability of signed patient information sheet (Informed Consent form) for participation in the clinical trial.

Exclusion Criteria:

  1. Acute diabetes mellitus complications for 3 months prior to inclusion in the trial (diabetic ketoacidosis, hyperosmolar hyperglycemic state, lacticemia, severe hypoglycemia and hypoglycemic coma).
  2. Diabetic retinopathy, preproliferative, proliferative or terminal stages (based on the results of oculist examination during screening period or 6 months prior to the trial).
  3. Diabetic nephropathy, proteinuria stage, chronic kidney disease on 3, 4 or 5 stage.
  4. Diabetic microangiopathy:

    • ishemic heart disease (medical history of a sudden coronary death with successful reanimation, medical history of myocardial infarction, stable exertional angina III or IV FC; unstable angina; post-infarction cardiosclerosis; chronic heart failure III or IV FC);
    • cerebrovascular diseases (medical history of acute cerebrovascular accident; progressive vascular leukoencephalopathy; vascular dementia);
    • chronic obliterative peripheral vascular diseases (clinically significant);
    • diabetic neuroosteoarthropathy;
    • diabetic foot (clinically significant).
  5. Heart rhythm disorder:

    • II-III atrioventricular block;
    • sick sinus syndrome;
    • long QT interval syndrome;
    • complete left bundle branch block;
    • block of 2/3 bundle branches;
    • WPW syndrome;
    • ventricular arrhythmia of III grade according Laun-Wolf;
    • paroxysmal supraventricular tachycardia;
    • paroxysmal/recurrent ventricular tachycardia;
    • atrial flutter and fibrillation;
    • ventricular flutter and fibrillation;
    • heart pacemaker implant.
  6. Uncontrolled arterial hypertension characterized by the following blood tension values: systolic blood pressure over 160 mm Hg and/or diastolic blood pressure over 100 mm Hg.
  7. Severe concomitant pathology including clinically significant cardiovascular diseases of III - IV functional class (according to New York Heart Association classification, 1964), nervous and endocrine system diseases, including morbid obesity (body mass index≥40.0 kg/m2), renal insufficiency, liver failure.
  8. Medical history of pancreatectomy or transplantation of pancreatic/islet cells.
  9. Medical history of renal transplantation.
  10. Malignant neoplasms/suspected malignant neoplasms.
  11. Exacerbations or decompensation of chronic diseases affecting a patient's ability to participate in the clinical trial.
  12. Level of fasting triglycerides >5.64 mmol/L.
  13. Medical history of bariatric surgical operations.
  14. Medical history of polyvalent allergy.
  15. Allergy/ intolerance to any of the components of medications used in the treatment.
  16. Intake of medicines listed in the section "Prohibited concomitant treatment" for 3 months prior to the inclusion in the trial.
  17. Pregnancy, breast-feeding.
  18. Drug addiction, alcohol usage in the amount exceeding 2 units of alcohol per day.
  19. Mental disorders of a patient.
  20. Night work.
  21. Participation in other clinical trials in the course of 3 months prior to the inclusion in the trial.
  22. Patients, who from the investigator's point of view, will fail to comply with the observation requirements of the trial or with the intake regimen of the investigated medicines.
  23. Other factors impeding patient's participation in the trial (for example, planned business trips or journeys).
  24. Patient is related to the research personnel of the investigative site, who are directly involved in the trial or are the immediate relative of the researcher. The immediate relative includes husband/wife, parents, children or brothers (or sisters), regardless of whether they are natural or adopted.
  25. Patient works for OOO "NPF "Materia Medica Holding" (i.e. is the company's employee, temporary contract worker or appointed official responsible for the carrying out the research) or the immediate relative.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01868594


Locations
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Russian Federation
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
Sponsors and Collaborators
Materia Medica Holding

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Materia Medica Holding
ClinicalTrials.gov Identifier: NCT01868594     History of Changes
Other Study ID Numbers: MMH-SU-003
First Posted: June 4, 2013    Key Record Dates
Results First Posted: March 4, 2019
Last Update Posted: May 30, 2019
Last Verified: May 2019

Keywords provided by Materia Medica Holding:
Combined treatment of patients with type I diabetes mellitus

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases