Neurotrauma

Can MLC901 Improve Cognitive Outcomes in Patients With Mild TBI?

Meghna Rao
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Publish Date
While MLC901 did not improve cognitive impairment after mild traumatic brain injury, it did improve other clinical outcomes including postconcussion symptoms, health related quality of life, anxiety, and depression.

Use of MLC901 (NeuroAiDTMII) after mild traumatic brain injury (TBI) results in significant improvements in some clinical outcomes, though it does not improve cognitive impairment. These results were published in PLOS One.

Researchers examined the cognitive benefits and safety of MLC901 in patients with cognitive impairment within 1 year of mild TBI in a phase 3, double-blind, multicenter study (ClinicalTrials.gov Identifier: NCT04861688). Patients (N=182) were randomly assigned to receive 2 capsules of 0.4 g each of MLC901 or matched placebo 3 times a week for 6 months. The primary efficacy outcome was complex attention at 6 months, assessed using the Central Nervous System Vital Signs cognitive test.

Among the participants, 92 were assigned to MLC90 and 90 to placebo. The mean (SD) ages were 40.6 (14.2) years in the MLC901 group and 40.1 (12.0) years in the placebo group. Men accounted for 50.0% and 47.8% of the participants, and nearly all were White (100.0% and 97.8%). Most mild TBIs (61%-62%) resulted from falls, and prior TBI was reported in 32.6% and 40.0% of the MLC901 and placebo groups, respectively.

At 6 months, adverse events occurred in 29.3% of the MLC901 group and 37.8% of the placebo group, with no serious events reported. The most common side effect was gastrointestinal symptoms, which occurred in 8.8% and 3.3% of the 2 cohorts, respectively. There were no statistically significant differences between MLC901 and placebo for complex attention (least-mean square difference, -1.18; 95% CI, -5.40 to 3.03; P =.58) or for secondary cognitive outcomes, including executive functioning, visual and verbal memory, processing speed, and reaction time.

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Although the trial was not able to detect treatment difference for the primary outcome… it was highly positive for all other important clinical post-TBI outcomes.

However, participants who received MLC901 had significant improvements in postconcussion symptoms, health related quality of life, anxiety, and depression at 6 months. These improvements remained at 9 months with MLC901 vs placebo, respectively:

  • Postconcussion symptoms improved by 47% (95% CI, 41%-53%) vs 29% (95% CI, 22%-35%)
  • Health related quality of life improved by 22% (95% CI, 18%-26%) vs 14% (96% CI, 11%-18%)
  • Anxiety improved by 49% (95% CI, 41%-57%) vs 42% (95% CI, 33%-51%)
  • Depression improved by 48% (95% CI, 39%-57%) vs 31% (95% CI, 22%-40%)

Study limitations include a lack of validation for the Central Nervous System Vital Signs cognitive test, as well as a lack of participant diversity.

The study authors concluded, “Although the trial was not able to detect treatment difference for the primary outcome… it was highly positive for all other important clinical post-TBI outcomes.”

Disclosures: This research was supported by Moleac Ple Ltd.

References:

 Pilipenko PI, Ivanova AA, Kotsiubinskaya YV, et al. 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. 2025;20(7):e0310229. doi:10.1371/journal.pone.0310229