Alzheimer's Drug May Be Neuroprotective in TBI

Deborah Brauser

August 04, 2017

A drug commonly used to treat Alzheimer's disease (AD) may also be beneficial for traumatic brain injury (TBI), new research suggests.

The randomized study of 41 adults with moderate TBI showed that those who received memantine (from Forest Labs and other manufacturers) plus standard TBI management had significantly greater reductions 7 days later in levels of serum neuron-specific enolase (NSE) compared with those who received standard management only. NSE is a common marker for neuronal damage.

The memantine-receiving group also had significantly greater score improvements on the Glasgow Coma Scale (GCS) just 3 days after treatment.

"Better neurological examinations, especially on the third day of the study and confirmed by NSE, were very surprising for our team," corresponding author, Mohammad Sistanizad, PhD, PharmD, Department of Clinical Pharmacy at Shahid Beheshti University of Medical Sciences, Tehran, Iran, told Medscape Medical News.

He noted that the overall findings are important to clinicians as they consider future outcomes. "Think about the level of functionality of the patients which you are discharging from hospital," said Dr Sistanizad.

Dr Mohammad Sistanizad

The findings were published online July 19 in the Journal of Clinical Pharmacology.

Defending the Injured Brain

Dr Sistanizad noted that because recovery of the brain after a trauma is difficult, numerous studies have examined modalities with neuroprotective effects to defend the injured brain from further neuronal loss.

"Unfortunately, none of the studies have shown promising results. Finding such an agent/agents could lead to important positive results in long-term outcome of the patients," he said.

Memantine is an N-methyl-D-aspartate (NMDA) receptor modulator that "has been studied for its possible neuroprotective properties," write the investigators. However, to the best of their knowledge, no randomized controlled trials have examined the effects of this NMDA receptor in humans with TBI, they add.

The researchers initially enrolled 68 adult patients with moderate TBI, defined as a baseline GCS score ranging from 9 to 12, at a hospital in Tehran between September 2012 and October 2013 (the higher the GCS score, the better). Twenty-seven participants were excluded for a variety of reasons, including oral intake intolerance, transfers, and deaths unrelated to the study, leaving 41 in the final analysis.

Of these patients, 22 (all but 1 of whom were men; mean age, 29.9 years) were randomly assigned to receive enteral memantine 30 mg twice a day for 7 days total —orally or through a nasogastric tube — plus standard TBI care.

Standard care followed hospital protocols based on the Brain Trauma Foundation guidelines, which were published in the Journal of Neurotrauma in 2007. Nineteen of the study participants (control group; all but 1 of whom were men; mean age, 31.2 years) were randomly assigned to standard care only.

The mechanisms of injury were motor vehicle accident for 19 and 16 members of the memantine and control groups, respectively, with falls being the cause for 3 members of each group.

Venous blood samples were collected from all participants at baseline and on days 3 and 7 to assess levels of NSE. Normal serum NSE levels range between 5 and 12 ng/mL.

Rapid NSE Normalization

At baseline, NSE levels did not differ significantly between the memantine group (21.46 ± 8.26 ng/mL) and the control group (23.34 ± 14.34 ng/mL), nor did GCS values.

However, the mean NSE levels were significantly lower/improved at 7 days and GCS scores were significantly higher/improved at 3 days for those receiving memantine plus standard care compared with those receiving only standard care.

Table. Outcomes Among Treatment Groups

Outcome Memantine + Standard Care Standard Care Only P Value
NSE levels at day 3 (ng/mL) 7.95 ± 2.86 12.33 ± 7.09 .05
NSE levels at day 7 (ng/mL) 5.03 ± 3.25 10.04 ± 5.72 .003
GCS score at day 3 12.3 ± 2.0 10.9 ± 1.9 .03

 

There was no difference between the two treatment groups in GCS scores at day 7, but that may be explained in part because GCS increased to near-normal at that time for both groups — and there was no follow-up to further elucidate the findings, note the investigators.

"Unfortunately, we were not able to follow these patients for long periods to perform functional scoring, and patients' medical charts were not available to find such data and outcomes," they write, adding that larger multicenter studies are also now needed.

Still, treatment with memantine "started quickly after moderate TBI resulted in a significant reduction of the neuronal damage marker NSE, which coincided with marked day-to-day improvements in GCS scores on all study days," the researchers conclude.

The study was funded by a grant from the vice chancellery for research affairs of Shahid Beheshti University of Medical Sciences. Dr Sistanizad reports having received research grants from the organization before. The other study authors have disclosed no relevant financial relationships.

J Clin Pharmacol. Published online July 19, 2017. Full article

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