NeuroAiD II™ (MLC901) in Mild Traumatic Brain Injury

Study Overview
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Brief Summary
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A Randomized Double-blind, Placebo-controlled, Multi-center Trial to determine the efficacy of NeuroAiD II™ (MLC901) in improvement of cognitive functioning of adult patients with long-term cognitive impairment following mild traumatic brain injury (mTBI) and to assess safety of NeuroAiD™ (MLC901) in these patients.

Official Title
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A Randomized Double-blind, Placebo-controlled, Multi-center Trial to Investigate the Efficacy and Safety of NeuroAiD II™ (MLC901) to Improve Cognitive Functioning in Non-surgical Mild Traumatic Brain Injury Patients

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Combination Product: Traditional Chinese Medicine (NeuroAiD II™ (MLC901)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with mild TBI, which occurred 1-12 months prior enrolment to the study. Mild TBI is defined as an external force from an incident causing injury to the brain and resulting in an altered level of consciousness. The mTBI diagnosis should be documented. Mild TBI is evidenced by any of the following: best Glasgow Coma Score 13-15 as assessed on scene, on admission and over next 3 days loss of consciousness for up to 30 minutes dazed and confused at the time of injury or post-TBI amnesia of < 24 hours duration. Patient experiencing cognitive impairment following injury, determined by the Cognitive Failures Questionnaire score >30. Adult male or female patients aged 18-65 years. The patient has signed an Informed Consent form (ICF) for participation in this study before initiation of study procedures. The patient can understand all protocol requirements, perform the study procedures, and agree to all limitations specified in the protocol. The patient agrees to use adequate contraception methods. Exclusion Criteria: Moderate or Severe TBI, determined by best Glasgow Coma Score of <13 (as assessed on scene, on admission and over next 3 days), or injury requiring neurosurgery (even if surgery was not done) Co-existing severe co-morbidity, including end stage renal failure, spinal cord injury, significant substance abuse, severe liver disease, significant mental illnesses, diabetes requiring insulin injections, severe agitation, advanced cancer or other severe conditions with life expectancy of less than 5 years. The decision on significance of the comorbidity for inclusion/exclusion from current study is made by the Investigator. Current participation in another clinical trial within 30 days. Women who are pregnant or who have a positive urine pregnancy test or breast-feeding. Not fluent in Russian language or have aphasia/dysphasia. No documented evidence of mTBI. Known allergy to MLC901/NeuroAiD II™ or any of its component ingredients. Other medical condition which in the opinion of the Principal Investigator would place undue risk on the patient if included in the trial or likely to interfere with NeuroAiD II™. History of psychic (including depressive) disorders, physical and other factors that do not allow for adequate self-assessment of one's behaviour and for compliance with the protocol requirements, including history of psychiatric disorders. Use of hormonal contraceptives, either oral or implant*.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NeuroAiD II™ (MLC901)<br>Recommended treatment is 2 capsules orally, 3 times a day (i.e. 6 capsules per day). Treatment is 12 weeks. | Combination Product: Traditional Chinese Medicine (NeuroAiD II™ (MLC901)<br>* NeuroAiD II™ (MLC901) contains the extracts of 9 botanical active ingredients blended with commonly used excipients. The 9 botanical active ingredients are traditional herbs well documented in the Pharmacopoeia of the People's Republic of China.<br>|
| Placebo Comparator: Placebo<br>Capsule 2 capsules orally, 3 times a day | Other: Placebo<br>* Placebo with same appearance as active intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central Nervous System Vital Signs (CNS-VS), Domain score: Complex Attention | Change in complex attention score, determined using Central Nervous System Vital Signs (CNS-VS) computer cognitive testing system, after 6 months of treatment compared to baseline in the group of patients receiving NeuroAiD II™ (MLC901), compared to the placebo group. In the domain dashboard, above average domain scores indicate a Standard Score (SS) greater than 109 or a Percentile Rank (PR) greater than 74, indicating a high functioning test subject. Average is a SS 90-102 or PR 25-74, indicating normal function. Low average is SS 80-99 or PR 9-24 indicating a slight deficit or impairment. Below average is SS 70-79 or PR 2-8, indicating moderate level of deficit or impairment. Very low is SS less than 70 or a PR less than 2, indicating a deficit and impairment. Lower score is better for Complex Attention. | 6 months of treatment compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CNS-VS system, Domain score: Execution Function | Changes in the scores for the following cognitive domains: executive functioning, determined by CNS-VS system, after 6 months of treatment compared to baseline, in the NeuroAiD II™ (MLC901) group, compared to the placebo group. In the domain dashboard, above average domain scores indicate a Standard Score (SS) greater than 109 or a Percentile Rank (PR) greater than 74, indicating a high functioning test subject. Average is a SS 90-102 or PR 25-74, indicating normal function. Low average is SS 80-99 or PR 9-24 indicating a slight deficit or impairment. Below average is SS 70-79 or PR 2-8, indicating moderate level of deficit or impairment. Very low is SS less than 70 or a PR less than 2, indicating a deficit and impairment. Higher score is better. | after 6 months of treatment compared to baseline | 
| CNS-VS system, Domain score: Processing speed | Changes in the scores for the following cognitive domains: processing speed, determined by CNS-VS system, after 6 months of treatment compared to baseline, in the NeuroAiD II™ (MLC901) group, compared to the placebo group. In the domain dashboard, above average domain scores indicate a Standard Score (SS) greater than 109 or a Percentile Rank (PR) greater than 74, indicating a high functioning test subject. Average is a SS 90-102 or PR 25-74, indicating normal function. Low average is SS 80-99 or PR 9-24 indicating a slight deficit or impairment. Below average is SS 70-79 or PR 2-8, indicating moderate level of deficit or impairment. Very low is SS less than 70 or a PR less than 2, indicating a deficit and impairment. Higher score is better. | after 6 months of treatment, compared to baseline | 
| CNS-VS system, Domain score: Visual memory | Changes in the scores for the following cognitive domains: visual memory, determined by CNS-VS system, after 6 months of treatment compared to baseline, in the NeuroAiD II™ (MLC901) group, compared to the placebo group. In the domain dashboard, above average domain scores indicate a Standard Score (SS) greater than 109 or a Percentile Rank (PR) greater than 74, indicating a high functioning test subject. Average is a SS 90-102 or PR 25-74, indicating normal function. Low average is SS 80-99 or PR 9-24 indicating a slight deficit or impairment. Below average is SS 70-79 or PR 2-8, indicating moderate level of deficit or impairment. Very low is SS less than 70 or a PR less than 2, indicating a deficit and impairment. Higher score is better. | after 6 months of treatment, compared to baseline | 
| CNS-VS system, Domain score: Verbal memory | Changes in the scores for the following cognitive domains: verbal memory, determined by CNS-VS system, after 6 months of treatment compared to baseline, in the NeuroAiD II™ (MLC901) group, compared to the placebo group. In the domain dashboard, above average domain scores indicate a Standard Score (SS) greater than 109 or a Percentile Rank (PR) greater than 74, indicating a high functioning test subject. Average is a SS 90-102 or PR 25-74, indicating normal function. Low average is SS 80-99 or PR 9-24 indicating a slight deficit or impairment. Below average is SS 70-79 or PR 2-8, indicating moderate level of deficit or impairment. Very low is SS less than 70 or a PR less than 2, indicating a deficit and impairment. Higher score is better. | after 6 months of treatment, compared to baseline | 
| CNS-VS system, Domain score: Reaction time | Changes in the scores for the following cognitive domains: reaction time, determined by CNS-VS system, after 6 months of treatment compared to baseline, in the NeuroAiD II™ (MLC901) group, compared to the placebo group. In the domain dashboard, above average domain scores indicate a Standard Score (SS) greater than 109 or a Percentile Rank (PR) greater than 74, indicating a high functioning test subject. Average is a SS 90-102 or PR 25-74, indicating normal function. Low average is SS 80-99 or PR 9-24 indicating a slight deficit or impairment. Below average is SS 70-79 or PR 2-8, indicating moderate level of deficit or impairment. Very low is SS less than 70 or a PR less than 2, indicating a deficit and impairment.Lower score is better. | after 6 months of treatment, compared to baseline | 
| Rivermead Post Concussion Symptoms Questionnaire (RPQ) | Change in the Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score, after 6 months of treatment, compared to baseline, in the NeuroAiD II™ (MLC901) group compared to the placebo group. Scoring system is in two groups. RPQ-3 is potentially 0-12 and a higher score is worse, requires closer monitoring. RPQ-13 score is potentially 0-52 where higher scores reflect greater severity. | after 6 months of treatment, compared to baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic Brain Injury, Randomized Double-blind, Placebo-controlled, NeuroAiD II™, MLC901, Traditional Chinese Medicine, Cognitive Functioning