Published: Jan 26, 2014
By John Gever, Deputy Managing Editor, MedPage Today
It sounds too good to be true — a noninvasive, benign-sounding treatment to help patients suffering strokes and head injuries recover cognitive and motor function.
That’s how near-infrared laser therapy (NILT) is being marketed to patients, typically by chiropractors. But the evidence behind it is extremely scant — some in vitro data, some animal experiments, and a few isolated case reports in human patients.
And the two largest clinical trials, conducted in patients with ischemic stroke, ended in failure. The trials sponsor declared bankruptcy last year.
The Rationale for NILT
Many studies have shown that electromagnetic radiation in the near-infrared — wavelengths just beyond the approximately 700-nm limit to human vision — can affect cell and organism biology. Some, but not all, of the induced changes can be attributed to the heat generated by absorption of near-infrared radiation.
Among the effects, seen in multiple cell and tissue types, is increased ATP synthesis in mitochondria — in essence, an energy jolt for the cell. This has particular relevance in the central nervous system because mechanical and chemical insults to brain neurons can result in impaired energy metabolism. It’s been hypothesized that raising these cells’ energy levels may keep them functioning — in other words, that near-infrared radiation may counterbalance the effects of injury.
Other in vitro and animal studies have suggested that near-infrared radiation may alter vascular tone to increase blood flow to the brain, and that it may promote differentiation of neuronal stem cells, perhaps by induction of neurotrophic growth factor expression.
The transformation of near-infrared radiation to NILT had its origins in the laboratory ofPaul Lapchak, PhD, of Cedars-Sinai Medical Center in Los Angeles, who had developed a rabbit model of acute embolic stroke considered to be a very close cousin to spontaneous ischemic stroke in humans.
A NILT device delivering moderate doses of radiation at 808 nm proved to be safe in this model. It also was effective, in terms of preserved motor function, when administered up to 6 hours after stroke onset. In a review Lapchak published in January 2012, he noted that this “therapeutic window” was longer than seen with thrombolytic drugs.
Clinical Studies in Stroke
A company called PhotoThera supported some of the animal studies, and with these data in hand, commenced a series of randomized clinical trials. The first, called NEST-1, was a phase II study in patients recruited within 24 hours of onset of acute ischemic stroke. Patients were assigned 2:1 to active NILT or a sham treatment.
At 90 days after treatment, functional measures were significantly better in the NILT group, with 59% having outcomes rated as “successful” (modified Rankin score of 0-2) compared with 44% of the control group (P=0.021).
That led to a 660-patient phase III trial with a similar design. However, it missed its primary endpoint of improvement as measured by modified Rankin score, with 36% of NILT patients achieving favorable outcomes versus 31% of controls (P=0.094).
Not to be dissuaded, PhotoThera raised $50 million from investors to support another phase III trial, called NEST-III. It was to enroll about 1,000 patients and also set modified Rankin score as the primary outcome measure. The trial began in late 2010 and was to be completed 2 years later.
But no results were ever released. PhotoThera’s acting CEO, Joe Melvin, told MedPage Todaythat it was stopped in October 2012 for futility.
“The futility determination was made using efficacy data on 566 patients from 48 stroke treatment centers in the U.S., Europe, Peru, and Canada,” Melvin said in an email.
PhotoThera filed for Chapter 7 bankruptcy — that is, complete liquidation — in May 2013.
Lapchak told MedPage Today that the stroke indication was not a good choice as the first application for NILT. The problem is the depth to which the radiation penetrates, he said.
In the small-animal models used in the preclinical studies, the radiation reached the entire brain. But humans’ thicker skulls and larger brains mean that the radiation reaches only the outer layers — not deep enough to affect motor function reliably.
Other Applications
Using NILT to preserve or restore cognitive function in patients with traumatic brain injury (TBI) has been studied by Margaret Naeser, PhD, of Boston University and the VA Boston Healthcare System.
Along with other researchers, she published results in 2011 with two TBI patients, with NILT administered long after the original injuries (5 years in one case; a history of multiple concussions going back at least 4 years in the other). Both showed significant improvements from baseline in measures of executive function and other aspects of cognition, according to their report in Photomedicine and Laser Surgery.
Naeser told MedPage Today that her group had submitted a paper on 11 additional TBI cases treated with transcranial NILT. Because it is currently under review, she declined to comment on the contents.
Similar positive findings have been reported in case reports of patients with Alzheimer’s disease, Parkinson’s disease, and some other neurological conditions.
NILT Marketing
Devices for delivering NILT are currently FDA approved for musculoskeletal pain indications, although in these indications it may simply act as a heat source. Consequently, these devices are readily available; they are commonplace in physiotherapy clinics and chiropractic offices, whose clienteles tend to be dominated by patients with pain complaints.
However, despite the very thin evidence base that NILT is effective for nonpain indications, some clinics market the technology for such purposes.
For example, the website for Riner Chiropractic Clinic in Flower Mound, Texas, advertises “stroke,” “windstroke” (a term originating in Chinese folk medicine that corresponds to either hemorrhagic or ischemic stroke), “chronic fatigue,” and a variety of other nonpain indications for NILT (the clinic did not respond to a request for comment).
MedPage Today first became aware of NILT’s marketing for nonpain neurological indications when a reader wrote for information.
The reader, who didn’t want to be identified, said her husband had fallen down stairs 3 years ago and struck his head.
Just a few days after the first two treatments, she said, “I have seen some cognitive changes and also with cooperation.”
The treatment, she said, was delivered by a chiropractor because that was the only locally available provider. “We are willing to do anything to help my husband,” she said.
By and large, U.S.-based NILT device makers with FDA clearances for pain indications do not appear to market them for other uses. Some foreign distributors, on the other hand, do make such claims.
Taiwan-based Konftec, for example, sells an infrared laser-equipped helmet for “brain stroke rehabilitation.”
Illegal?
One domestic vendor with no FDA clearances on record does sell an infrared device directly to consumers for treating “Alzheimer’s disease, brain injuries, Parkinson [sic] and dementia.”
Sold by Little Elm, Texas-based Emerson WorldWide (no relation to Emerson Electric), the device resembles a 1950s floor lamp. Though the firm calls it a helmet, photos indicate that it’s actually a stand with five gooseneck lamps attached. The user bends the necks until the lamps are directly against his or her head.
As justification for the various neurological treatments, Emerson cites Naeser’s TBI studies, a 2008 British report on a different type of NILT device in a single Alzheimer’s disease patient, and a patient testimonial.
Emerson sells the product — “built on request, Special Order, nonreturnable” — for a regular price of $2,795, but “on sale limited time” at $2,100.
The FDA’s 510(k) and pre-market approval databases show no record of any approval or clearance for Emerson WorldWide. The firm did not respond to a request for comment. TheDallas-area Better Business Bureau reported that it contacted Emerson in 2012 “to request substantiation for several product efficacy claims” for a number of its products. However, the firm “failed to modify or provide substantiation for its claims,” the report said.