Clinical research is the study of health and disease in humans. There are two main types of clinical research studies – clinical trials and observational studies.

Participation in clinical trials is essential to advance science and find effective treatments for ALS. Every clinical trial participant helps researchers learn about more about the safety and efficacy of potential treatments as well as the underlying biology of the disease. Participation in clinical trials can also provide people living with ALS a chance to access an investigational treatment.

By participating in an observational study, you can help researchers learn more about ALS. Data from observational studies can inform research into new treatments, uncover potential biomarkers, and improve care for people living with ALS. In some observational studies, such as ALS TDI's ALS Research Collaborative (ARC), you may be able to access and view the data you contribute which could provide insight into your progression and help inform decisions about your care.

A placebo contains no active ingredients but is made to resemble a treatment in its appearance and delivery method. For example, sugar pills might be substituted for an oral medication or a saline injection for an intravenous medication. In clinical trials, placebos are used to account for the “placebo effect,” a phenomenon in which some people may experience health benefits from the psychological effects of believing that they are receiving treatment. The group of participants receiving placebo also serve as a control group and allow for clearer analyses of whether positive or negative outcomes in the trial could be related to an investigational treatment. It is helpful to know that most clinical trials today will allow participants to take other currently approved treatments.

Most clinical trials will have a placebo group. However, some trials, referred to as “open label trials”, do not feature a placebo group and all participants will receive active treatment. These open label trials are more common in phase 1 and 2 studies , because at these stages trials are generally more focused on safety or analyzing how a drug behaves in the body, rather than efficacy. Additionally, some trials may have an “open label extension,” a period after the completion of the study in which all participants – even those that previously received a placebo – are given the active treatment. Open label extensions can continue to provide investigational drug access to trial participants while providing investigators data about its evaluate its long-term effects. Valuable data on what happens when people switch from placebo to active treatment can also be acquired in this way.

A randomization ratio represents the ratio of participants who will be given the treatment vs. those who will receive a placebo. For example, in a trial with a 3:1 randomization ratio, three participants will receive the treatment for every one participant who receives a placebo.

Some trials may have more complicated randomization ratios. For example, a trial that is testing more than one dosage of a treatment might have a randomization ratio of 1:1:1. In this case, this would mean that an equal number of participants would receive a smaller dose of the treatment, a larger dose, or a placebo.

In a blinded trial, participants are not informed if they are on placebo or active drug to account for the placebo effect. In a double-blinded trial, neither the participants nor the investigators know who is on placebo or active drug to help protect against bias when they analyze the trial data.

By participating in a trial, you are helping to move research forward and bring us closer to new approved ALS treatments. As an individual participating in a trial, you may also be able to access a new treatment – something that is important to consider in a disease like ALS with limited treatment options.

There are many potential issues that are important to consider when thinking about enrolling in a clinical trial, including

There are many considerations when choosing a trial. You may use the resources and information in ALS TDI's tools to understand your priorities for participation in research. Your priorities may include an interest in a particular investigational drug, participating at a site within a specific distance from your home, or avoiding an investigational treatment that might require invasive procedures like surgery, for example. Having a better understanding of your priorities may help you have a well-informed discussion with your care team about the best options for you. Ultimately nobody knows whether a trial will be successful, but having a clear understanding of participation expectations, the trial design, and the risks and benefits of trial participation can be helpful in guiding your choices.

Genetic testing can provide helpful information as you access approved treatments and look for trials. About 15% of ALS currently is known to have a genetic basis, and it is important to understand that people with or without a family history of ALS may carry an ALS related genetic mutation. Genetic testing guidelines published in 2023 recommend that all people living with ALS should at minimum be offered testing. A discussion with a genetic counselor can provide information on the implications of testing for other family members, guidance for family planning, as well as considerations for disability and life insurance.

Some trials may be exclusively for people with a certain genetic mutation, and knowing your genetic status may provide opportunities for trials you could enroll in that might be more targeted to your specific case of ALS. In other cases, certain genetic mutations may exclude someone from trials that may not have a strong scientific rationale for treating those mutations.

If you decide that you want to participate in a clinical trial or study, you should start looking for one as soon as possible. Many trials have criteria excluding people based on the amount of time that has passed since their first ALS symptom. The sooner you start looking, the more trials you may be eligible for.

It can be challenging, even for ALS research sites, to know of all available research opportunities. ALS TDI's trial finder gathers information from multiple sources to provide a comprehensive view of options that are available.

First, it is important to discuss your participation in a trial with your medical team. Then, you should reach out to the trial site where you would like to enroll.

Contact information for trial sites and sponsors can be found in the ALS TDI clinical trials database. You should also be able to find this information at clinicaltrials.gov or other global trial registries, and sometimes on the trial sponsor's website.

Screening processes for clinical trials can vary. In general, once you contact a site, you will be asked to visit the site for an examination and a medical history will be collected to ensure you meet the eligibility criteria for a trial. Baseline tests like blood collection or breathing evaluation may be run.

This will vary from trial to trial. Many trials will allow participants to access approved medications, but some may not due to their study design – particularly if the medication in question was approved after a trial began recruiting participants. To determine if a trial allows approved medications, consult the trial’s inclusion and exclusion criteria and be sure to ask the trial sponsor or site for more information.

This will vary from trial to trial. Many trials will allow participants to access approved medications, but some may not, due to their study design – particularly if the medication in question was approved after a trial began recruiting participants. To determine if a trial allows approved medications, consult the trial's inclusion and exclusion criteria and be sure to ask the trial sponsor or site for more information.

Inclusion criteria are the conditions that a participant must meet to enroll in a trial. These might include being in a certain age range, having a diagnosis of definite or probable ALS, having a vital capacity above a certain range, having the ability to swallow, or being on a stable dose of approved ALS medications.

Exclusion criteria are the factors that will make a potential participant ineligible to enroll in a study. These may include using invasive or non-invasive ventilation, taking certain drugs or supplements, having other co-occurring diseases like cancer, or being pregnant.

Many trials may limit participation based on the time since you first experienced ALS symptoms. Others may similarly limit participation based on the time since you received an ALS diagnosis. While some studies may not limit participation based on these factors, most trials for investigational ALS treatments do. It is important to carefully consider the inclusion and exclusion criteria when considering participation in any clinical trial. Observational studies generally have much broader eligibility criteria and can be an impactful way to contribute to ALS research.

If you don’t meet the initial requirements for a trial, you may have other options, including:

There are several common routes of administration – or ways that a drug is administered – in ALS. They include:

It is important to consider which routes of administration are acceptable to you. For example, are you willing to undergo an invasive procedure, such as surgery or a spinal tap for an intrathecal injection? Or are you able to swallow well enough to take a medication in pill form?

Researchers conducting a clinical trial are legally required to present potential participants with detailed information about the risks and benefits of the treatment in question. This is to allow participants to make an informed decision about whether they wish to enroll. This process, called "informed consent," will usually involve reading and signing a series of documents covering the requirements for participating in the trial, the known adverse effects, other risks of the treatment, and other relevant information.

If you are participating in a blinded or double-blinded trial, you will not be informed if you are on placebo or active drug. You may be provided with this information after the study’s conclusion if the results are unblinded.

Most trials will not provide you with access to personal data from your participation in the study. As the trial is ongoing, sharing your personal data could unblind the trial.

Required in-person visits will vary depending on the trial. This information may be available in a trial’s online description, but generally, the best way to find out is to reach out to a trial site or sponsor.

Travel costs may be reimbursed in some – but not all – trials. To find out if a trial you are interested in will reimburse your travel costs, contact the trial site.

In the US, federal law guarantees that clinical trial participants can end their participation at any time without incurring any penalty.

When a trial is unblinded, the participants are informed whether they were on active drug or placebo. This generally occurs after the last participant completes participation in the trial and its open label extension.

An open label extension is a period after the completion of the blinded phase of a trial in which all participants are given the active drug.

After the completion of a trial, you may be able to continue to receive the treatment at the discretion of the trial sponsor.

A placebo is a substance made to resemble a treatment that contains no active ingredients. For example, sugar pills might be substituted for an oral medication, or a saline injection for an intravenous medication. In clinical trials, placebos are used to account for the “placebo effect,” a phenomenon in which some people may experience beneficial health outcomes simply from the psychological effects of believing that they are receiving treatment.

The process by which clinical trial participants are randomly assigned to different groups within the study. This may be between a group on active drug or a placebo, groups receiving different dosages of a drug, or both.

In a blinded trial, participants are not informed if they are on placebo or active drug to account for the placebo effect.

The researcher, or group of researchers, that oversee preparing and carrying out a clinical trial.

There are four main phases of clinical trials:

A study for the purpose of testing the safety and/or efficacy of an investigational treatment for a disease in human participants.

A study in which researchers collect data about people with a disease without giving them any “intervention” or treatment. Some observational studies are also called natural history studies.

A program in which a trial sponsor provides access to an investigational treatment for people who would not otherwise be able to participate in a trial.

A US government program through which individuals can apply to a trial sponsor to access an investigational treatment.

The way in which a medication is delivered to the body. Some common routes of administration include oral medications like pills or liquids, injections into the veins, muscles, or spinal cord, or a surgical procedure.

A biomarker is a biological characteristic that can tell doctors or scientists something about a disease. Some common biomarkers associated with diseases include blood glucose levels for diabetes or LDL cholesterol for heart disease. There are currently no biomarkers in ALS that are able to accurately measure disease progression or the effectiveness of treatments.