Enrolling the first patient always takes the most time.
There’s the process, explaining the goals of the clinical study and what will be needed from the participant.
But once that first one signs on, the study opens up and the number of patients enrolled increases exponentially. Researchers end up learning the most from the first patient as well.
That’s the case for the ALL-ALS study at the Indiana University School of Medicine, which enrolled its first patient in April.
ALL-ALS is a clinical study with the goal of uncovering the causes of Amyotrophic Lateral Sclerosis (ALS) by determining biomarkers and examining the genetics of individuals who either have ALS or have a first-degree relative who has been diagnosed with the disease.
Also known as Lou Gehrig's disease, ALS is a rare, terminal neurodegenerative disease that weakens muscles throughout the body. It can occur in anyone, anywhere, at any age and has no known cure. Researchers at the IU School of Medicine work to understand the disease and search for a cure while making life as comfortable as possible for those who are affected.
Biomarkers are biological indicators that researchers and physicians use to track and diagnose diseases. Examples of commonly used biomarkers include a patient’s blood pressure, body temperature and hormone count.
Cynthia L. Bodkin, MD, an associate professor of clinical neurology at the IU School of Medicine, is the primary investigator for the ALL-ALS study’s site in Indianapolis. In that role, Bodkin oversees all aspects of the study from patient enrollment to staff management.
Samples and data collected from patients in the study include spinal fluid, breath analysis and measures for tracking how a patient’s voice changes over time as the disease progresses.
ALL-ALS is the first study of its kind, Bodkin said, and ALS diagnosis and treatment will be made easier if the study is able to uncover biomarkers that let researchers track the disease and predict its progression.
If researchers can track and predict the disease’s progression, it’ll make studying it easier as well. They wouldn’t need to wait six months or even a year to see if a new treatment is working, Bodkin said.
“We may be able to figure that out in a couple of months,” Bodkin said.
ALL-ALS came together remarkably quickly, Bodkin said. Between patient enrollment, National Institutes of Health funding and putting together a detailed plan for sample collection and data analysis, the study has been going well.
“I think the overall interest in finding a cure and desire to find a cure for ALS has gotten physicians and groups and people to work together to understand that this is important and we need to streamline this process,” Bodkin said. “It’s important to get things moving forward as fast as possible because lives depend on it.”
Collaborative research for a cure
This kind of study, along with other research at IU School of Medicine and elsewhere, is critical to the ultimate goal: finding a cure for ALS.
“If you don’t have research, whether it’s basic science research or clinical trials, we’re never going to find a cure,” Bodkin said.
Research into ALS and other diseases is separated into multiple branches, including basic science studies, translational research and clinical trials. Basic science research delves into underlying structures of disease and biological processes while clinical research focuses on direct application with the goal of improving patient care.
Basic science research into ALS at the IU School of Medicine is led by researchers like Brian Pierchala, PhD, the Sherry Sonneborn Professor of ALS Research, who focuses on motor neurons, nerve cells that transmit information from the brain and spinal coordinating movement throughout the body. Findings from Pierchala’s foundational science studies help researchers understand the mechanisms of ALS and work toward new therapies to apply in the clinic.
Researchers like Bodkin provide specialized, firsthand care to patients to help minimize their symptoms and improve their quality of life.
Clinical trials go through four phases with the first three studying the effects of a new treatment or drug on increasingly larger groups of patients to track signs of improvement and possible side effects. Most clinical studies for ALS involve testing new drug therapies to determine if they are effective at treating symptoms of neurodegeneration and loss of muscle control.
Researchers spend large amounts of time with patients during the first phase of a trial, which involves a small group of patients. Specific measurements for ALS involve measuring patients’ muscle strength for signs of change.
Bodkin and her colleagues enjoy spending time with ALS patients. The researchers have a saying that says: “The ALS gene is right next to the nice gene.”
“The patients with ALS tend to be very thankful and nice and grateful for anything you do,” Bodkin said. “It’s a horrible disease that tends to happen to wonderful people."
Unfortunately, many clinical trials for ALS have ended in Phase 1 when it becomes apparent that the drug isn’t working as anticipated. Some studies, however, move on to Phase 2, during which researchers investigate long-term safety and evaluate whether the evidence is strong enough to move to the final phase of clinical trials. Frustratingly, many studies don’t make it to Phase 3.
Speeding up discovery
The HEALEY trial is another first-of-its-kind study that Bodkin is working on at the IU School of Medicine. It’s unique in that it’s a Platform Trial, meaning multiple different drugs and treatments are being applied and tracked with one group.
The ultimate goal behind the HEALEY trial is to reduce the amount of time it takes for a treatment to move along in the four phases. Rather than focusing on one specific drug or treatment, the trial is focused on the overall disease itself.
“The speed of the trial is much faster,” Bodkin said. “For every patient that gets ALS, they’re fighting time. If we can find this cure faster, that’s a significant benefit.”
The volume of clinical studies into ALS provides hope for researchers and patients alike, Bodkin said, with studies being the only way to ultimately find a cure.
She sees a potential breakthrough on the horizon with recent discoveries in determining the genetic aspects of the disease, although most ALS cases are sporadic and not linked to family history.
The potential for ultimately finding a cure comes down to the ability to do clinical trials and having patients willing to sign on.
“That makes my job worth doing,” Bodkin said. “We do this because we want to give people with ALS hope and come up with a cure for them.”
