In a continuous effort to evaluate curative therapies for amyotrophic lateral sclerosis (ALS), Duke will soon be conducting a new pilot study that administers curcumin—an ingredient found in turmeric and curry powder associated with reduced inflammation—to evaluate the degree to which the microbiome in patients with ALS can be changed over time, potentially decreasing the rate of disease progression.
The second-of-its-kind Replication of ALS Reversal (ROAR) trial at Duke is based in part on a 2018 review published by ALSUntangled, an organization with an international group of researchers that assesses crowd-sourced alternative and off-label treatments (AOTs), with the goal of helping people with ALS make more informed decisions about them.
Duke neurologist and director of the Duke ALS Clinic Richard S. Bedlack Jr., MD, PhD, who leads ALSUntangled, says that although the use of curcumin as a therapy is controversial, there are more than 12,000 scientific papers referencing its use. This trial will include a specific brand of curcumin that has the potential to be absorbed and enter the brain and study whether the microbiome is different in patients with ALS compared to healthy controls.
Unprecedented ROAR Trial Structure
Most ALS trials look for a relatively small effect of slowing disease progression, with a homogenized population and tight study inclusion criteria. However, the structure of the ROAR trials is unprecedented, Bedlack says: trials are conducted almost entirely in a virtual setting and do not use placebos. Participants are evaluated through telemedicine, and no in-person visits are required. What’s more, almost anyone with ALS can participate in these trials—“they just need to be able to use the Internet and participate for six months,” he adds.
The data for ROAR trials are entered into an online database by patients on an ongoing basis, which makes data readily searchable during the trials. “This way, patients don't have to wait years to find out the results of one of these trials; they can find out in real time and decide whether it’s something they would want to do,” Bedlack says.
Counseling Patients on AOTs for ALS
Bedlack encourages clinicians to provide patients with ALS a roadmap for conducting their own systematic review of therapies for potential experimentation. “We know that people with ALS can't wait, and it's just human nature for people to want to try things,” he says. “Any time there's a disease that's disabling, life-shortening, or incurable, people turn to the Internet, and there's no shortage of extraordinary claims, many of which are not backed up with any kind of useful information,” Bedlack says. Through trials like this one and through ALSUntangled reviews, however, he says “sometimes we find that the most outrageous things turn out to be incredibly promising, and things that some people still don't believe in turn out to be absolutely real.”
With access to the Institutional Review Board-approved protocol for ROAR trials, even patients who live in remote areas are able to self-experiment with reasonably safe and reasonably priced therapies that look promising in terms of their mechanism or anecdotal data. “People can read our protocol and find out why and how we are studying this, where we are getting the product, what dosage we are using, and what outcomes we are following. This gives patients a roadmap to work with their own doctor and try the same thing that we're trying,” Bedlack says.
Bedlack suggests sharing with patients the following list of red flags he published through ALSUntangled that outlines areas of concern when patients are considering trying a product or trial they come across online. “A physician could say, ‘Let’s look together at these red flags and ask ourselves how many of these things apply to this particular product or trial. If there are a lot, we may want to consider something else.’ We’ve got to find a way to be optimistic for our patients, respectful of their ideas, and responsive to their questions. If we use our years of scientific training to help them, then I think they will make more informed and better decisions about Internet products they are considering.”
When counseling patients about alternative and off-label therapies they may be considering as potential treatment, Bedlack’s list below of red flags may help in the discussion of a treatment’s claims:
