Back to resultsEfficacy and Safety Clinical Trial of Tenoten for Children Liquid Dosage Form Therapy in Infants With Sequelae of Perinatal Brain Injury
Primary Purpose
Sequelae of Perinatal Brain Injury
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Tenoten for children
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Sequelae of Perinatal Brain Injury
Eligibility Criteria
Inclusion Criteria:
- Full-term infants aged 29 days to 9 months.
- Diagnosis of Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischemia and/or mild-to-moderate intracranial hemorrhage).
- Total Jurba-Mastyukova score of < 27 (but > 12).
- Physical development parameters within 25-27 centiles.
- Neurologist's outpatient observation.
- Information sheet (informed consent form) for parents/adoptive parents for participation in the clinical study signed by the child's parents/adoptive parents.
Exclusion Criteria:
Previously diagnosed lesions, diseases and conditions:
1.1. Cerebral ischemia (grade III). 1.2. Intraventricular hemorrhage (grade III). 1.3. Metabolic and toxic disorders affecting central nervous system (persistent neonatal hypoglycemia, hyperbilirubinemia associated with elevated indirect bilirubin, and other severe conditions).
1.4. Intracranial birth injury, focal impairments due to brain injuries (pareses and paralyses).
1.5. Sequelae of birth injury to spinal cord, cranial nerves and peripheral nervous system (peripheral pareses and paralyses).
1.6. Different types of hydrocephalus. 1.7. Symptomatic epilepsy and epileptic syndromes. 1.8. Sequelae of perinatal central nervous system (CNS) infectious diseases (injury to CNS caused by neonatal sepsis, encephalitis, meningitis, meningoencephalitis, ventriculitis).
1.9. Infectious diseases including congenital diseases (cytomegalovirus infection, rubella, herpesvirus or enterovirus infection, toxoplasmosis, syphilis, HIV infection, etc.).
1.10. Chronic respiratory diseases originating in the perinatal period, including bronchopulmonary dysplasia.
1.11. Hereditary metabolic diseases including glycogen storage disease (glycogenoses, E74.0), galactose metabolism disorders (galactosemia, Е74.2), other carbohydrate metabolism disorders (Е74), glucosaminoglycan metabolism disorders (mucopolysaccharidoses, Е76), aromatic amino-acid metabolism disorders (phenylketonuria, tyrosinemia, etc, Е70), branched-chain amino-acid and fatty-acid metabolism disorders (maple-syrup-urine disease, Е71), mitochondrial myopathy (G71.3).
1.12. Neurogenerative diseases including Huntington disease (G10), copper metabolism disorder (Wilson disease, Е83.0).
1.13. Chromosomal abnormalities. 1.14. Congenital anomalies [malformations] and deformities including congenital anomalies of nervous system and malformations of internal organs.
1.15. Congenital endocrine diseases (congenital hypothyroidism, hypoparathyroidism, adrenocortical dysfunction).
1.16. Malignant neoplasm / suspected malignant neoplasm.
- Acute infectious disease, exacerbation / decompensation of diseases that may prevent the patients' participation in the clinical study.
- Allergy/intolerance of any of the study treatment medications components.
- Drug addiction, alcohol use in the volume over 2 alcohol units/day by the subject's parent(s)/adoptive parent(s).
- Mental disorders of the patient's parent(s)/adoptive parent(s).
- Participation in other clinical studies for a period prior to and during the course of this trial.
- Other conditions complicating the subject's participation in the study (cannot make regular medical visits, moving, etc.).
- Subjects whose parent(s)/adoptive parent(s), from the investigator's point of view, will not follow the study requirements or comply with the dosing regimen.
- Patients whose parent(s)/adoptive parent(s) are related research staff of the clinical investigative site who are directly involved in the study or is a close relative of the investigator. Close relatives include spouse, parents, children or brothers (sisters) regardless of whether they are biological or adoptive ones.
- Patients whose parent(s)/adoptive parent(s) is working in OOO "NPF "Materia Medica Holding", i.e. is the company official, temporary contract worker or an appointed official responsible for the study or their close relatives.
Sites / Locations
- State Budgetary Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital of Rehabilitation The Scientific and Practical Center "Bonum"
- Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University" of the Ministry of Healthcare of the Russian Federation
- Pirogov Russian National Research Medical University
- I.M. Sechenov First MSMU
- Moscow Regional Research and Clinical Institute ("MONIKI")
- Municipal Health Care Institution "City Child Health Clinical Polyclinic №5"
- State budgetary institution of public health of the Samara region "Samara City Children's Clinical Hospital No. 1 named after N.N. Ivanova"
- LLC "Center for DNA Research"
- LLC Nebbiolo
- Federal State Budgetary Educational Institutionof Higher Education "Yaroslavl State Medical University" of the Ministry of Healthcare of the Russian Federation
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tenoten for children
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment
The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as "age-appropriate normal value"; 23-26 points - as "an absolute risk group"; 13-22 points - as "developmental retardation"; below 13 points - as "severe global developmental delay".
Secondary Outcome Measures
Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as "age-appropriate normal value"; 23-26 points - as "an absolute risk group"; 13-22 points - as "developmental retardation"; below 13 points - as "severe global developmental delay".
Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery; the score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test; the score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills; the score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients [DQ = (developmental age/chronologic age)*100]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development).
Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery. The score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test. The score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills. The score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients [DQ = (developmental age/chronologic age)*100]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development).
Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course.
The Clinical Global Impressions - Efficacy Index (CGI-EI) scale provide an evaluation of the treatment response. CGI-EI takes account of both therapeutic efficacy and treatment-related adverse events and ranges from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03159611
Brief Title
Efficacy and Safety Clinical Trial of Tenoten for Children Liquid Dosage Form Therapy in Infants With Sequelae of Perinatal Brain Injury
Official Title
Multicenter Double-blind Placebo-controlled Parallel-group Randomized Clinical Trial of Efficacy and Safety of Tenoten for Children Liquid Dosage Form Therapy in Infants With Sequelae of Perinatal Brain Injury
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
February 19, 2016 (Actual)
Primary Completion Date
February 9, 2018 (Actual)
Study Completion Date
February 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Materia Medica Holding
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Purpose of the study:
To assess the clinical efficacy of Tenoten for children liquid dosage form therapy (10 oral drops per day for 12 weeks) in Infants with Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischaemia and/or mild-to-moderate intracranial haemorrhage).
To assess the safety of Tenoten for children liquid dosage form therapy (10 oral drops per day for 12 weeks) in Infants with Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischaemia and/or mild-to-moderate intracranial haemorrhage).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sequelae of Perinatal Brain Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
182 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tenoten for children
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Tenoten for children
Intervention Description
Oral. 10 drops daily, at the same time in the morning, 15 minutes before feeding.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral. 10 drops daily, at the same time in the morning, 15 minutes before feeding.
Primary Outcome Measure Information:
Title
Percentage of Patients With a 4 and More Point Increase of the Total Score According to Jurba-Mastyukova Psychomotor Development Scale by the End of the Treatment
Description
The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as "age-appropriate normal value"; 23-26 points - as "an absolute risk group"; 13-22 points - as "developmental retardation"; below 13 points - as "severe global developmental delay".
Time Frame
in 12 weeks of the treatment
Secondary Outcome Measure Information:
Title
Percentage of Patients With Normal Psychomotor Development (≥ 27 Scores on Jurba-Mastyukova Scale) by the End of Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
Description
The Jurba-Mastyukova scale is meant to evaluate motor and mental development of 1-12-month-old infants. 10 developmental domains are evaluated every month. The evaluation of each domain is based on a 4-point system (the optimal development equals 3 points, its absence = 0 points). The maximum score is 30 points; 27-29 points are considered as "age-appropriate normal value"; 23-26 points - as "an absolute risk group"; 13-22 points - as "developmental retardation"; below 13 points - as "severe global developmental delay".
Time Frame
in 12 weeks of the treatment
Title
Mean Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Score by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
Description
The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery; the score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test; the score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills; the score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients [DQ = (developmental age/chronologic age)*100]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development).
Time Frame
in 12 weeks of the treatment
Title
Percentage of Patients With Normal Psychomotor Development (CATS/CLAMS + Gross Motor Developmental Quotients Score ≥ 75) by the End of the Treatment Course Compared to Baseline (Time Frame: 0 Weeks, 4 Weeks, 8 Weeks, 12 Weeks)
Description
The Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) Consists of Three batteries: Clinical adaptive test (CAT), clinical linguistic and auditory milestone scale (CLAMS), and Gross motor (GM). CAT is the visual-motor problem-solving battery. The score on the CAT is based on the child's performance with the administered items. CLAMS is the language battery of the test. The score on the CLAMS is based on the parent's report of language skill attainment. GM evaluates motor skills. The score on the GM is based on the direct observation of a child and examination by the neurologist. The scores from the CAT/CLAMS+GM are expressed as developmental quotients [DQ = (developmental age/chronologic age)*100]. The full-scale CAT/CLAMS+GM DQ (full-scale DQ) is the mean of the CAT DQ, the CLAMS DQ, and GM DQ. Full-scale DQ ≥ 75 is considered as normal value (the child has a normal development).
Time Frame
in 12 weeks of the treatment
Title
Clinical Global Impression Scale - Efficacy Index (CGI-EI) Score by the End of the Treatment Course.
Description
The Clinical Global Impressions - Efficacy Index (CGI-EI) scale provide an evaluation of the treatment response. CGI-EI takes account of both therapeutic efficacy and treatment-related adverse events and ranges from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects).
Time Frame
in 12 weeks of the treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
29 Days
Maximum Age & Unit of Time
9 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Full-term infants aged 29 days to 9 months.
Diagnosis of Sequelae of Perinatal Brain Injury (mild-to-moderate cerebral hypoxia-ischemia and/or mild-to-moderate intracranial hemorrhage).
Total Jurba-Mastyukova score of < 27 (but > 12).
Physical development parameters within 25-27 centiles.
Neurologist's outpatient observation.
Information sheet (informed consent form) for parents/adoptive parents for participation in the clinical study signed by the child's parents/adoptive parents.
Exclusion Criteria:
Previously diagnosed lesions, diseases and conditions:
1.1. Cerebral ischemia (grade III). 1.2. Intraventricular hemorrhage (grade III). 1.3. Metabolic and toxic disorders affecting central nervous system (persistent neonatal hypoglycemia, hyperbilirubinemia associated with elevated indirect bilirubin, and other severe conditions).
1.4. Intracranial birth injury, focal impairments due to brain injuries (pareses and paralyses).
1.5. Sequelae of birth injury to spinal cord, cranial nerves and peripheral nervous system (peripheral pareses and paralyses).
1.6. Different types of hydrocephalus. 1.7. Symptomatic epilepsy and epileptic syndromes. 1.8. Sequelae of perinatal central nervous system (CNS) infectious diseases (injury to CNS caused by neonatal sepsis, encephalitis, meningitis, meningoencephalitis, ventriculitis).
1.9. Infectious diseases including congenital diseases (cytomegalovirus infection, rubella, herpesvirus or enterovirus infection, toxoplasmosis, syphilis, HIV infection, etc.).
1.10. Chronic respiratory diseases originating in the perinatal period, including bronchopulmonary dysplasia.
1.11. Hereditary metabolic diseases including glycogen storage disease (glycogenoses, E74.0), galactose metabolism disorders (galactosemia, Е74.2), other carbohydrate metabolism disorders (Е74), glucosaminoglycan metabolism disorders (mucopolysaccharidoses, Е76), aromatic amino-acid metabolism disorders (phenylketonuria, tyrosinemia, etc, Е70), branched-chain amino-acid and fatty-acid metabolism disorders (maple-syrup-urine disease, Е71), mitochondrial myopathy (G71.3).
1.12. Neurogenerative diseases including Huntington disease (G10), copper metabolism disorder (Wilson disease, Е83.0).
1.13. Chromosomal abnormalities. 1.14. Congenital anomalies [malformations] and deformities including congenital anomalies of nervous system and malformations of internal organs.
1.15. Congenital endocrine diseases (congenital hypothyroidism, hypoparathyroidism, adrenocortical dysfunction).
1.16. Malignant neoplasm / suspected malignant neoplasm.
Acute infectious disease, exacerbation / decompensation of diseases that may prevent the patients' participation in the clinical study.
Allergy/intolerance of any of the study treatment medications components.
Drug addiction, alcohol use in the volume over 2 alcohol units/day by the subject's parent(s)/adoptive parent(s).
Mental disorders of the patient's parent(s)/adoptive parent(s).
Participation in other clinical studies for a period prior to and during the course of this trial.
Other conditions complicating the subject's participation in the study (cannot make regular medical visits, moving, etc.).
Subjects whose parent(s)/adoptive parent(s), from the investigator's point of view, will not follow the study requirements or comply with the dosing regimen.
Patients whose parent(s)/adoptive parent(s) are related research staff of the clinical investigative site who are directly involved in the study or is a close relative of the investigator. Close relatives include spouse, parents, children or brothers (sisters) regardless of whether they are biological or adoptive ones.
Patients whose parent(s)/adoptive parent(s) is working in OOO "NPF "Materia Medica Holding", i.e. is the company official, temporary contract worker or an appointed official responsible for the study or their close relatives.
Facility Information:
Facility Name
State Budgetary Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital of Rehabilitation The Scientific and Practical Center "Bonum"
City
Ekaterinburg
ZIP/Postal Code
620149
Country
Russian Federation
Facility Name
Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University" of the Ministry of Healthcare of the Russian Federation
City
Kazan
ZIP/Postal Code
420012
Country
Russian Federation
Facility Name
Pirogov Russian National Research Medical University
City
Moscow
ZIP/Postal Code
117997
Country
Russian Federation
Facility Name
I.M. Sechenov First MSMU
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Facility Name
Moscow Regional Research and Clinical Institute ("MONIKI")
City
Moscow
ZIP/Postal Code
129110
Country
Russian Federation
Facility Name
Municipal Health Care Institution "City Child Health Clinical Polyclinic №5"
City
Perm
ZIP/Postal Code
614066
Country
Russian Federation
Facility Name
State budgetary institution of public health of the Samara region "Samara City Children's Clinical Hospital No. 1 named after N.N. Ivanova"
City
Samara
ZIP/Postal Code
443079
Country
Russian Federation
Facility Name
LLC "Center for DNA Research"
City
Saratov
ZIP/Postal Code
410005
Country
Russian Federation
Facility Name
LLC Nebbiolo
City
Tomsk
ZIP/Postal Code
634034
Country
Russian Federation
Facility Name
Federal State Budgetary Educational Institutionof Higher Education "Yaroslavl State Medical University" of the Ministry of Healthcare of the Russian Federation
City
Yaroslavl
ZIP/Postal Code
150000
Country
Russian Federation
12. IPD Sharing Statement
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Efficacy and Safety Clinical Trial of Tenoten for Children Liquid Dosage Form Therapy in Infants With Sequelae of Perinatal Brain Injury
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