Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury : A Randomized Clinical Trial

Key Points

Question

Is near-infrared low-level light therapy (LLLT) feasible and safe after moderate traumatic brain injury, and does LLLT affect the brain and exhibit neuroreactivity?

Findings

In this randomized clinical trial including 68 patients with moderate traumatic brain injury who were randomized to receive LLLT or sham therapy, 28 patients completed at least 1 LLLT session without any reported adverse events. In the late subacute stage, there were statistically significant differences in the magnetic resonance imaging–derived diffusion parameters of the white matter tracts between the sham- and light-treated groups, demonstrating neuroreactivity of LLLT.

Meaning

The results of this clinical trial show that transcranial LLLT is feasible, safe, and affects the brain in a measurable manner.

Abstract

Importance

Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response.

Objectives

To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment.

Design, Setting, and Participants

A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted.

Interventions

Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem).

Main Outcomes and Measures

The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group.

Results

Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: −0.018; 95% CI, −0.026 to −0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91).

Conclusions and Relevance

In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response.

Trial Registration

ClinicalTrials.gov Identifier: NCT02233413

Abstract

This randomized clinical trial evaluates the effect of near-infrared low-level light therapy in patients with traumatic brain injury from the time of injury until 3 months after the injury.