Although approved for use in treating traumatic brain injury (TBI) in nearly 60 countries, use of citicoline in a randomized trial that included more than 1,200 participants with TBI did not result in improved functional and cognitive status, according to a study led by Ross Zafonte, the Earle P. and Ida S. Charlton Professor of Physical Medicine and Rehabilitation at HMS and head of the Department of Physical Medicine and Rehabilitation of the Spaulding Rehabilitation Network.
Citicoline is an endogenous compound that offers potential neuroprotective properties as well as post-injury neurorepair. It is widely used in the U.S. by patients with a range of neurologic disorders, yet it had not previously been evaluated in a large randomized clinical trial for TBI. Citocoline is available as a food supplement, or nutraceutical.
“This is an important point to stop and review some approaches when using nutraceuticals for TBI populations,” said Zafonte. “The breadth and depth of this study severely calls into question some assumptions that have been made on citicoline and certainly merits further study.”
The results were published in the Nov. 21 issue of JAMA, the Journal of the American Medical Association.
The paper reported that “despite considerable advances in emergency and critical care management of TBI as well as decades of research on potential agents for neuroprotection or enhanced recovery, no effective pharmacotherapy has yet been identified.”
Citicoline is readily available in the U.S. as an over-the-counter nutraceutical, with some research showing it can assist with improving focus and brain activity. This has led to some patients using it to treat attention-deficit disorder (ADD). In Europe and Japan it is also used in TBI and stroke patients.
Zafonte and colleagues from a nationwide consortium conducted the study to evaluate the efficacy of citicoline for improving cognitive and functional status among patients with TBI. The Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3 randomized clinical trial, was conducted between July 2007 and February 2011. The study, which included 1,213 patients at eight level-1 trauma centers in the U.S., examined the effects of 90 days of enteral or oral citicoline (2,000 mg) vs. placebo initiated within 24 hours of injury in patients with complicated mild and moderate/severe TBI.
The researchers found that the citicoline and placebo groups did not differ significantly on measures of cognitive and functional status at the 90-day evaluation.
There was no significant treatment effect in the two severity subgroups (moderate/severe and complicated mild TBI). In patients with moderate/severe TBI, no statistically significant difference was observed between treatment groups at the 180-day evaluation.
The overall proportion of patients reporting serious adverse events was similar between the placebo and citicoline groups.
“The COBRIT study indicates that citicoline was not superior to placebo as an acute and postacute therapy among participants with a broad range of severity of TBI. The worldwide use of citicoline for TBI should now be questioned,” Zafonte said.
This story is adapted from a news release from Spaulding Rehabilitation Network.
