In April 2006, when Dave Bexfield was diagnosed with relapsing-remitting multiple sclerosis (MS) at the age of 37, one of the first things he did was go snowboarding. In that same week he founded http://activemsers.org, a website designed to inspire other people with MS to “be as active as possible, regardless of disability,” he says.
MS, a condition that occurs when the immune system attacks the central nervous system, damaging the myelin sheath that protects nerve cells, includes symptoms such as tingling, numbness, pain, fatigue, poor balance, blurred vision, weakness in one or more limbs, stiffness, urinary problems, and even cognitive decline as the disease progresses. In relapsing-remitting MS, symptom flare-ups (relapses) are followed by periods of remission.
Patients with MS sometimes feel hopeless and inert. Bexfield, an outdoorsy world traveler, launched his website to help address those feelings in himself and others. Within weeks of his diagnosis, he started taking a disease-modifying drug and volunteered for a three-year clinical trial, which was testing an add-on medication. At the conclusion of the trial he found out he was in the placebo group, which turned out to be immaterial because the add-on drug showed no benefit. Over the three years, Bexfield continued to snowboard, hike, and travel.
But in 2009, being active got tougher. He tried another disease-modifying drug and relapsed after four months. His neurologist switched him to a third drug, which also failed. “Within three years of diagnosis I was using a walker,” Bexfield recalls. “Things were going downhill quickly. I couldn't tie my shoes, clip my fingernails, or press the nozzle on my deodorant.” Eventually, his condition deteriorated to the point where he could no longer walk the length of his living room. As Bexfield repeatedly emphasizes on his website, his case “is NOT the norm. Not even close. Really.”
Alarmed, Bexfield and his doctors decided to get aggressive and consider a clinical trial called HALT-MS. The trial, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), involved an autologous stem cell transplant, a three-week hospital stay, and temporary relocation to Texas.
In an autologous stem cell transplant, patients' stem cells are harvested from their blood. After several rounds of chemotherapy to eliminate red blood cells, the stem cells are transplanted back into patients to “jump start” the immune system. Bexfield knew the treatment carried considerable risks: Because the chemotherapy destroys the immune system, the risk of death due to a secondary infection was approximately one in 20. The chemotherapy also makes patients sterile and increases the risk of a blood disease such as leukemia over the following decade.
The benefits of autologous stem cell transplants have been seen in aggressive forms of relapsing MS, but not in progressive MS, although researchers aren't sure why, notes Robert J. Fox, MD, FAAN, a neurologist at the Mellen Center for MS in Cleveland. Early trials of stem cell therapy included people with primary progressive and secondary progressive MS, but the risks of death and complications were too high, so researchers shifted the focus to people with aggressive relapsing-remitting MS.
After meeting the trial requirements—a diagnosis of less than 15 years, at least two relapses in the past 18 months despite taking medication, and the ability to walk 100 meters without a cane—Bexfield signed up. In February 2010, he and his wife relocated to Houston and stayed at the MD Anderson Cancer Center. On March 25, his immune system was “rebooted” with his stem cells.
In the end, the risks were worth it, says Bexfield. From the time of his transplant until 2015, his MS symptoms improved in almost every way. “After the transplant, I could walk 500 meters again,” he recalls. “My cognitive problems got better. I could use my deodorant again.” Bexfield produced a video about his stem cell therapy experience and submitted a version of it to the American Academy of Neurology's annual Neuro Film Festival (http://NeuroFilmFestival.com) in 2011, which won the Fan Favorite award (http://bit.ly/NFF-FanFavorite).
In mid-2015, Bexfield's MS symptoms slowly began to reappear, and walking became difficult again. After five and a half years of taking no medication, he resumed disease-modifying therapy. Now he uses forearm crutches, a walker, and a wheelchair as he and his wife continue to travel the globe, from Madrid, Spain to Machu Picchu in Peru.
Not every patient in a clinical trial sees improvements like Bexfield's, but many researchers have found that patients who enroll in clinical trials tend to have more favorable outcomes, whether they receive treatment or a placebo.
In clinical trials, patients often end up seeing new doctors or multiple doctors and share much more information with the medical team than a typical patient would, says Bruce H. Cohen, MD, FAAN, director of the NeuroDevelopmental Science Center at Akron Children's Hospital. The intense and often prolonged personalized treatment may lead to improved outcomes, he suggests. “Doctors may ultimately provide medical advice that patients wouldn't benefit from had they not participated in a trial,” Dr. Cohen says. “Sometimes we hear information that allows us to figure out something we wouldn't have otherwise in an office visit.”
Andrea Andretta has certainly found this to be true. A former kindergarten teacher, Andretta was forced to retire in November 2011 after being diagnosed with fibromyalgia and chronic fatigue syndrome (CFS). In 2012, she joined a clinical trial under the supervision of her doctor, one of the lead researchers in the trial. Four times a year, Andretta traveled from her home in Connecticut to her doctor's office in Manhattan to fill out a questionnaire and deliver stool, urine, and blood samples to be filed in a biobank. The samples, collected from Andretta and hundreds of other patients with CFS, will be researched and compared to healthy patients in a future phase of the trial.
Andretta has never received a placebo or an experimental treatment, but she has benefitted regardless. During one questionnaire, she realized that her rapid resting heart rate could be an abnormality caused by her CFS. After bringing it to the attention of her doctor, Andretta was referred to a cardiologist, who modified her diet and brought her heart rate back to normal. “I am more knowledgeable about my illness because of those questionnaires,” she says.
Andretta continues to donate samples and advance the science of her disease in any way she can. “I'm open to participating in a study and finding out something that can help me or anybody else,” she says.
RARE DISEASES ON THE RADAR
Clinical trials benefit more than just the individual patient, says George Yohrling, PhD, senior director of Mission and Scientific Affairs at the Huntington's Disease Society of America (HDSA). Huntington's disease is known as an “orphan disease,” meaning it affects fewer than 200,000 patients in the United States at any given time. In the early 1980s, Congress rallied to pass the Orphan Drug Act of 1983, which provided pharmaceutical companies longer patent protections and larger tax breaks on clinical trials that benefit rare diseases. By 2015, 47 percent of novel drugs approved by the US Food and Drug Administration were used to treat orphan diseases.
For this reason, Dr. Yohrling considers recruiting patients his most important job at the HDSA. “For years, we've been asking, ‘Where are the drugs?’ Now we can say, ‘The drugs are here.’ We need to see if these treatments are effective, and as quickly as possible. With Huntington's disease, time is not on our side.”
SLOW TO PARTICIPATE
Despite the importance of clinical trials and the potential benefits for patients, the percentage of people who actually sign up is low. In 2011, an analysis by the National Institutes of Health published in Clinical Trials found that 19 percent of trials that year were terminated due to lack of enrollment.
Why the low enrollment? “First, to be in a clinical trial, you have to both have an illness and be able to get out of bed,” Dr. Cohen says, which is harder for patients with more severe symptoms. Furthermore, patients may not have the support they need to join a trial, even if they want to.
“I have one patient flying in from rural northwestern Canada to participate,” Dr. Cohen says. “His family has to be highly motivated to drive a couple of hours to their airport, fly to Chicago, connect to a flight to Cleveland, and then drive to the medical center for treatment.” This is repeated every few weeks until the study concludes, but some studies take years of participation.
Patients also may not meet inclusion criteria. “To gain study entrance, one must be sick enough so that doctors can measure the illness, but well enough to participate in the evaluation to see if the treatment is working,” Dr. Cohen explains. This automatically excludes patients who are mildly affected and, arguably, have the most to gain, but also excludes those with more debilitating symptoms.
Finally, despite the need for placebo-controlled trials using medications that may have unknown or severe side effects, the likelihood of side effects or the use of placebos is another reason people stay away from clinical trials, Dr. Cohen says.
Patients may fear getting a placebo instead of a new therapy, but in fact most new therapies turn out not to be effective and to have side effects, which is why patients in clinical trials who get the placebo usually do somewhat better than those who get the new therapy, says Gary Gronseth, MD, FAAN, vice chair of neurology at the University of Kansas Medical Center in Kansas City. The only way researchers can determine if a drug is effective is to compare how people do on the new therapy to how others do on placebo or a standard therapy.
Pat Furlong, founder of Parent Project Muscular Dystrophy (PPMD), an advocacy group for families affected by muscular dystrophy, has been involved in clinical trials for Duchenne muscular dystrophy (DMD) since 1984, when two of her children were diagnosed with the condition. Since their deaths in 1994, Furlong has championed research initiatives for families whose children have DMD.
But many families, she finds, are unwilling or unable to get on board. “It can be uncertainty or inconvenience,” Furlong says. And because DMD typically appears in boys around the age of 3, parents may also be reluctant to subject their sons to the rigors of a trial.
To allay parents' fears, PPMD conducts workshops around the country and at an annual conference in June to share information. “We talk about optimal care, which trials exist, and what the protocols look like,” Furlong says. “Then we encourage parents to participate.”
Trial participation, Furlong says, is crucial to finding a cure for such a debilitating and progressive disease. “The only way you can have a drug approved and a company pay for it is to prove it works,” she says. And some clinical trials have proven beneficial for patients with DMD: Thanks to a 1994 trial that tested the efficacy and safety of steroids for people with DMD, for example, steroids are commonly used today to prolong muscle strength.
HOW TO GET INVOLVED
Even if volunteering is daunting, there are other ways to move science forward, says Dr. Yohrling.
In 2012, the CHDI (Cure Huntington's Disease Initiative) Foundation launched a registry to track patients and their symptoms over the course of several years and asked patients to volunteer information. “When a pharmaceutical company has a drug that might work for a particular disease, the first questions are, ‘Where are the patients and how can we test it?’” says Dr. Yohrling. “A robust patient registry could help expedite clinical trials.”
Furlong, whose organization created a patient registry in 2007, says registries can help researchers recruit patients. “Companies see where most patients are located and can recruit based on age, genetics, or degree of function,” she says.
In addition to joining a patient registry, Bexfield recommends diet- or exercise-based trials. “It's an easier way to step into trials,” he says. “You might have no side effects at all.”
The most important thing is to get involved however you can. “It may seem scary,” Bexfield admits. “But if we're going to find a cure for neurologic diseases, researchers need volunteers. If we're afraid to participate, the research won't move forward.”
How to Find a Clinical Trial
Ask your doctor. Let your doctor know of your interest in participating in a trial. He or she may know of appropriate trials or may even be involved in one—or may be able to keep an eye out for any upcoming studies.
Search http://clinicaltrials.gov. With a database of more than 230,000 studies around the globe, patients can search for trials by disease, location, recruitment status, or drug. Patients can also see the results of past studies posted in the database.
Go to a conference. Often, doctors and researchers will attend conferences to discuss upcoming research and recruit patients for potential trials.
Check local universities. Medical schools with certain specialties, such as the University of Southern California, which houses a pain center, may either be hosting a clinical trial or know of others who are actively recruiting.
Join a support group. In some chapter meetings for the Huntington's Disease Society of America (HDSA), volunteers visit support groups and answer questions in the community about upcoming clinical trials. In the past, researchers and physicians leading these trials have attended these groups to provide additional information, says George Yohrling, PhD, of the HDSA.