What Are Clinical Trials?

Clinical trials and observational studies are the two main types of clinical research. Clinical trials, also called interventional trials, usually focus on evaluating new treatments, while observational studies generally give researchers a better understanding of how a disease progresses with current treatment options. 

In the United States, the FDA requires new drugs and other treatments to be tested in a series of progressively larger clinical trials to find out if they are both safe and effective. The FDA uses the information collected during these trials to decide whether to approve the investigational treatment for other people living with ALS to use.  

On this page, we answer some common questions about ALS clinical trials: 

Clinician and patient

Why Are Clinical Trials Important? 

Clinical trials are essential for making ALS livable for everyone, everywhere. Researchers use clinical trials to find out whether new treatments are safe and beneficial for people living with ALS. Clinical trials also help find better ways to prevent, detect and diagnose ALS, or to improve quality of life through things like assistive technologies or social support. 

What Happens during a Clinical Trial? 

The most common type of clinical trial is called a randomized, double-blind, placebo-controlled trial. During this type of trial, researchers introduce an intervention, like taking a new drug, and then study the effects compared to a placebo, an inactive substance that looks the same and is given in the same way as the active drug being tested. Since this type of trial is randomized, participants are randomly assigned to receive either the investigational drug or a placebo. It is called double-blind because neither the participants nor the researchers know who is getting the drug and who is getting the placebo.   

Throughout the trial, the research team gathers information from each participant through questionnaires, physical exams and/or by collecting blood or other samples. The researchers then analyze what happens to the people in each group based on the study protocol (research plan). Using statistics, the researchers are able to determine if any differences in outcomes, such as improved function or slower disease progression, were caused by the drug. 

Many people worry that if they participate in a clinical trial, they will receive a placebo. Because participants are randomly assigned to their treatment group, this is always a possibility. However, to help make ALS research more patient-centered, many ALS clinical trials are designed so more participants receive the investigational treatment than the placebo. 

What Are the Phases of Clinical Trials? 

Clinical trials move through several phases that build on one another to find the best dose, identify side effects and understand the effects of the drug or treatment on ALS. Knowing the phase of the clinical trial can help you understand how many people have already tried the treatment being studied and how much is known about it. 

Pilot trial – This is a small study that can help researchers find out more about the safety and side effects of a drug, look for biomarkers related to ALS or evaluate a study’s design for use in larger trials. Pilot trials may also involve testing a drug approved for another disease in people living with ALS. 

Phase 1 – These trials are often testing investigational treatments for the first time in humans. Because of this, the drug is only given to a small group, often 20 or fewer people. Participants are closely monitored for any adverse reactions or side effects. If any appear that are considered to be too dangerous, testing is stopped, and the drug will not advance any further in the clinical trial process. 

Phase 2 – During this phase, researchers are trying to determine the best dose, route of administration (by mouth, by injection, etc.) and timing of doses for the investigational treatment. Information about the treatment’s ability to benefit the health or function of people with ALS may also be gathered. These preliminary results are helpful in starting to figure out whether the investigational treatment might be effective for people with ALS, but more testing in larger groups of people is needed to know for sure. Usually for ALS, less than 100 people are involved in a phase 2 trial. 

Phase 3 – This stage of testing involves enough participants to determine whether or not a treatment is effective. Phase 3 trials for ALS usually involve hundreds of participants. Such large numbers of participants are required because ALS symptoms and progression can be so different from person to person. Typically, investigational treatments are submitted to the FDA for approval once phase 3 testing is complete. 

Phase 4 – Phase 4 trials continue to monitor the effectiveness and safety of a drug or treatment after it has been approved by the FDA. 

Who Can Participate in Clinical Trials? 

Because clinical trials need to produce reliable data to support FDA approval, people with ALS must have certain characteristics to be eligible to participate. These characteristics, known as “inclusion criteria,” can vary from trial to trial but may include age, time since diagnosis, lung function (measured by forced vital capacity [FVC] and/or slow vital capacity [SVC]), functional status (measured by the ALSFRS-R) and/or specific ALS-linked gene mutations. Trials also have a list of “exclusion criteria” that would make someone ineligible to participate. Your doctor or a clinical trial team member can talk with you about whether you might be eligible for a specific trial.   

How Do I Find a Clinical Trial? 

We are partnering with a global health technology company called myTomorrows to provide free personalized clinical trial navigation services. myTomorrows navigators are available to help people living with ALS and their loved ones identify and understand all available clinical trial options and to provide support throughout the enrollment process. If you are interested, you can schedule a call with a patient navigator through the myTomorrows website and receive a personalized overview of trial options to discuss with your doctor. 

We also partner with the Northeast ALS Consortium (NEALS) to provide the most accurate and up-to-date information about both federally and privately funded ALS clinical trials and observational studies. People with ALS and their caregivers can search the online database or connect with a NEALS ALS trial liaison by calling 855-437-4823 or emailing alstrials@neals.org. The liaison can answer your questions about participating in research and assist with finding and/or enrolling in a trial.

Click here for more information about finding ALS research opportunities. 

What Can I Expect if I Join a Clinical Trial? 

Here’s an overview of what you can expect if you decide to participate in a trial: 

  • A clinical trial team member will explain the research in detail and gather more information about you. 
  • You will have time to ask questions and make sure you understand what participation will mean. 
  • If you decide to participate, you will sign an informed consent form. 
  • A clinical trial team member will then continue the screening process. This can include a physical examination (e.g., height, weight, blood pressure, lung capacity) and questions about your medical history. The type and number of assessments required will depend on the study protocol (research plan). 
  • If you are eligible to participate and enroll in the trial, you will attend your first visit, which is often called the “baseline” visit. 
  • You will be randomly assigned to receive either the investigational treatment or a placebo. In most cases, neither you nor your doctor will be told if you are getting the drug or a placebo so this information does not influence the results of the trial.   
  • You and your caregiver will follow the research staff’s instructions on how and when you will receive any additional doses.  
  • You may need to return to the trial site at regularly scheduled times or these follow-up visits may occur virtually. During these visits, the research team may ask you to fill out questionnaires, do an exam and/or collect samples. 
  • You should tell the research staff about any side effects, issues or concerns you have along the way. 
  • You will continue to see your regular doctor throughout the study as well. 
  • You can choose to stop participating in the trial at any time, for any reason. 

Can Family Members of People with ALS Participate in Clinical Trials?

Currently, there is only one clinical trial for people with familial ALS but no symptoms of the disease. The phase 3 ATLAS Study, is testing tofersen in approximately 150 participants who have specific SOD1 gene mutations but do not have any signs or symptoms of ALS. Through this study, the researchers are trying to determine whether tofersen can delay the onset of signs or symptoms of ALS and/or slow declines in function once signs or symptoms appear. 

What Is an Institutional Review Board (IRB)?

An Institutional Review Board (IRB) is an independent group of people who review and monitor biomedical research to ensure the welfare, rights and privacy of research participants. IRBs must approve studies involving human participants before they begin. IRBs continue to monitor studies along the way to ensure researchers follow ethical principles and federal regulations. 

How Does The ALS Association Support Clinical Trials?

Thanks to the generosity of our supporters, we invest millions of dollars each year to increase the number of – and access to – high-quality ALS clinical trials. 

Through our Lawrence and Isabel Barnett Drug Development Program, we support the preclinical assessment of emerging ALS therapies and drive the crucial transition from laboratory research project to industry drug development effort. This stage is often referred to as the “valley of death” since promising biomedical ideas often wither and die at this point due to a lack of funding. By supporting projects at this stage, the Barnett Drug Development Program helps fill this funding gap and has contributed to the expansion of companies and therapeutics entering ALS clinical trials.   

We also support early stage (phase 1 and 2a) clinical trials of new or repurposed approaches for treating ALS with our Hoffman ALS Clinical Trial Awards Program. These grants serve to “de-risk” clinical programs by supporting early-stage trials with clear go/no-go criteria that, if positive, can be used to attract follow-on funding and enable later stage development. 

In addition, we recognize that bolstering ALS clinical trial infrastructure is crucial to accelerating the development of new and effective treatments. In 2020, we provided foundational funding for the HEALEY ALS Platform Trial, which tests and evaluates multiple investigational treatments simultaneously. We also support NEALS, which has more than 20 years of experience developing and conducting multicenter ALS clinical trials. Finally, we launched our Trial Capacity Awards in 2022 to increase access to ALS clinical trials, especially for those in underserved populations, and help improve the efficiency and pace at which these studies are conducted. 

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