A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury.
<h4>Introduction</h4>About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. Although up to 40% of adults with mild TBI experience persistent functional deficits, there is no proven-effective trea...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0310229 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849715135810109440 |
|---|---|
| author | Pavel I Pilipenko Anna A Ivanova Yulia V Kotsiubinskaya Vera N Grigoryeva Alexey Y Khrulev Anatoly V Skorokhodov Maxim M Gavrik Nona N Mkrtchan Marek Majdan Peter Valkovic Daria Rabarova Suzanne Barker-Collo Kelly Jones Valery L Feigin |
| author_facet | Pavel I Pilipenko Anna A Ivanova Yulia V Kotsiubinskaya Vera N Grigoryeva Alexey Y Khrulev Anatoly V Skorokhodov Maxim M Gavrik Nona N Mkrtchan Marek Majdan Peter Valkovic Daria Rabarova Suzanne Barker-Collo Kelly Jones Valery L Feigin |
| author_sort | Pavel I Pilipenko |
| collection | DOAJ |
| description | <h4>Introduction</h4>About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. Although up to 40% of adults with mild TBI experience persistent functional deficits, there is no proven-effective treatment to facilitate recovery after it.<h4>Methods and analysis</h4>This randomized placebo-controlled multi-centre study was aimed to examine the efficacy of herbal supplement MLC901 on complex attention following mild TBI at 6 months post-randomisation, as a primary outcome measured by CNS Vital signs (CNS-VS). Adults aged 18-65 years, who were 1-12-months post-mild TBI and experienced cognitive impairment, were randomly assigned to receive either MLC901 two capsules (0.4g/capsule) or placebo three times a day for 6 months using centralized stratified permuted block randomization. Secondary outcomes: Rivermead Post-Concussion Symptoms Questionnaire (RPQ; neurobehavioral sequelae); Health Related Quality of Life (QOLIBRI); Hospital Anxiety and Depression Scale (HADS); and safety. Mixed effects models of repeated measures with intention to treat analysis were employed. A Least Square Mean Difference (LSMD) from baseline to 3-, 6-, and 9-month follow-up was calculated with 95% confidence intervals (CI).<h4>Results</h4>In the analysis, 182 participants (47.8% females) were included. Multivariable mixed effects model analysis did not reveal significant improvements in complex attention (LSMD = -1.18 [95% CI -5.40; 3.03; p = 0.58]) and other cognitive domains at 6 months in the MLC901 group compared to the Placebo group. There were significant improvements in RPQ, QOLIBRI, anxiety and depression in the MLC901 group compared to the Placebo group at 6 and 9 months (LSMD -4.36 [-6.46; -2.26] and -4.07 [-6.22; -1.92], 4.84 [1.58; 8.10] and 3.74 [0.44; 7.03], -1.50 [-2.29; -0.71 and -0.96 [-1.84; -0.08], -1.14 [-1.92; -0.35] and -1.14 [-1.94; -0.34]), respectively. MLC901 tested was proven safe.<h4>Conclusions</h4>Although the 6-month treatment with MLC901 did not result in a statistically significant difference with placebo for CNS-VS measurement of cognitive domains in individuals with mild TBI, the study showed a clinically and statistically significant improvement in all clinical scales assessed by the investigators.<h4>Trial registration</h4>ClinicalTrials.gov identifier NCT04861688. |
| format | Article |
| id | doaj-art-5333e656d10a4e27be0669ca5ebaa14c |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-5333e656d10a4e27be0669ca5ebaa14c2025-08-20T03:13:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e031022910.1371/journal.pone.0310229A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury.Pavel I PilipenkoAnna A IvanovaYulia V KotsiubinskayaVera N GrigoryevaAlexey Y KhrulevAnatoly V SkorokhodovMaxim M GavrikNona N MkrtchanMarek MajdanPeter ValkovicDaria RabarovaSuzanne Barker-ColloKelly JonesValery L Feigin<h4>Introduction</h4>About half of the world population will suffer from a traumatic brain injury (TBI) during their lifetime, of which about 90% of cases are mild TBI. Although up to 40% of adults with mild TBI experience persistent functional deficits, there is no proven-effective treatment to facilitate recovery after it.<h4>Methods and analysis</h4>This randomized placebo-controlled multi-centre study was aimed to examine the efficacy of herbal supplement MLC901 on complex attention following mild TBI at 6 months post-randomisation, as a primary outcome measured by CNS Vital signs (CNS-VS). Adults aged 18-65 years, who were 1-12-months post-mild TBI and experienced cognitive impairment, were randomly assigned to receive either MLC901 two capsules (0.4g/capsule) or placebo three times a day for 6 months using centralized stratified permuted block randomization. Secondary outcomes: Rivermead Post-Concussion Symptoms Questionnaire (RPQ; neurobehavioral sequelae); Health Related Quality of Life (QOLIBRI); Hospital Anxiety and Depression Scale (HADS); and safety. Mixed effects models of repeated measures with intention to treat analysis were employed. A Least Square Mean Difference (LSMD) from baseline to 3-, 6-, and 9-month follow-up was calculated with 95% confidence intervals (CI).<h4>Results</h4>In the analysis, 182 participants (47.8% females) were included. Multivariable mixed effects model analysis did not reveal significant improvements in complex attention (LSMD = -1.18 [95% CI -5.40; 3.03; p = 0.58]) and other cognitive domains at 6 months in the MLC901 group compared to the Placebo group. There were significant improvements in RPQ, QOLIBRI, anxiety and depression in the MLC901 group compared to the Placebo group at 6 and 9 months (LSMD -4.36 [-6.46; -2.26] and -4.07 [-6.22; -1.92], 4.84 [1.58; 8.10] and 3.74 [0.44; 7.03], -1.50 [-2.29; -0.71 and -0.96 [-1.84; -0.08], -1.14 [-1.92; -0.35] and -1.14 [-1.94; -0.34]), respectively. MLC901 tested was proven safe.<h4>Conclusions</h4>Although the 6-month treatment with MLC901 did not result in a statistically significant difference with placebo for CNS-VS measurement of cognitive domains in individuals with mild TBI, the study showed a clinically and statistically significant improvement in all clinical scales assessed by the investigators.<h4>Trial registration</h4>ClinicalTrials.gov identifier NCT04861688.https://doi.org/10.1371/journal.pone.0310229 |
| spellingShingle | Pavel I Pilipenko Anna A Ivanova Yulia V Kotsiubinskaya Vera N Grigoryeva Alexey Y Khrulev Anatoly V Skorokhodov Maxim M Gavrik Nona N Mkrtchan Marek Majdan Peter Valkovic Daria Rabarova Suzanne Barker-Collo Kelly Jones Valery L Feigin A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury. PLoS ONE |
| title | A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury. |
| title_full | A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury. |
| title_fullStr | A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury. |
| title_full_unstemmed | A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury. |
| title_short | A double-blind, placebo-controlled, randomized, multi-centre, phase III study of MLC901 (NeuroAiDTMII) for the treatment of cognitive impairment after mild traumatic brain injury. |
| title_sort | double blind placebo controlled randomized multi centre phase iii study of mlc901 neuroaidtmii for the treatment of cognitive impairment after mild traumatic brain injury |
| url | https://doi.org/10.1371/journal.pone.0310229 |
| work_keys_str_mv | AT pavelipilipenko adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT annaaivanova adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT yuliavkotsiubinskaya adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT verangrigoryeva adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT alexeyykhrulev adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT anatolyvskorokhodov adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT maximmgavrik adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT nonanmkrtchan adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT marekmajdan adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT petervalkovic adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT dariarabarova adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT suzannebarkercollo adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT kellyjones adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT valerylfeigin adoubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT pavelipilipenko doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT annaaivanova doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT yuliavkotsiubinskaya doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT verangrigoryeva doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT alexeyykhrulev doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT anatolyvskorokhodov doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT maximmgavrik doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT nonanmkrtchan doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT marekmajdan doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT petervalkovic doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT dariarabarova doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT suzannebarkercollo doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT kellyjones doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury AT valerylfeigin doubleblindplacebocontrolledrandomizedmulticentrephaseiiistudyofmlc901neuroaidtmiiforthetreatmentofcognitiveimpairmentaftermildtraumaticbraininjury |