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How Do Clinical Trials Work for SMA?

Medically reviewed by Evelyn O. Berman, M.D.
Written by Joan Grossman
Posted on September 15, 2022

  • Clinical trials for spinal muscular atrophy (SMA) test new treatments, new dosages of existing treatments, or new combinations of drugs with volunteers.
  • Clinical trials are designed to advance research and improve care for people living with SMA.
  • Access to a new treatment approach may provide health benefits, but there is no guarantee.
  • Clinical trials are designed to protect the safety of the participants, although there is still a risk of side effects.

People with spinal muscular atrophy — and parents of children with SMA — may be curious about how clinical trials work. Clinical trials are a part of medical research, in which people volunteer to participate in the study of a particular health condition. In SMA clinical trials, most if not all participants are people who have SMA.

Volunteers in clinical trials may be asked to try new drugs, dosages, or combinations of drugs; test medical devices, undergo medical procedures, or change behaviors — such as diet or exercise — so researchers can develop more effective treatments and standards of care. Clinical trials are essential for the advancement of health care.

Medical research on SMA has evolved considerably in recent years. Numerous clinical trials are underway to find safer, more effective ways to help slow or delay the progression of SMA and improve quality of life. This article explains how clinical trials are generally set up.

New Treatment Research for SMA

This is an exciting time for SMA research. In recent years, the U.S. Food and Drug Administration (FDA) approved the first three drugs for treating SMA, and many more new treatment approaches are now in clinical trials. For people with SMA, genetic mutations limit muscle function and lead to muscle loss. The drugs currently approved are innovative gene therapy treatments that act on the survival motor neuron (SMN) genes SMN1 and SMN2, which control muscle and motor function.

Using the disease-modifying drugs nusinersen (Spinraza), risdiplam (Evrysdi), and onasemnogene abeparvovec-xioi (Zolgensma), some people with SMA have seen significant improvements in motor function, motor milestones, and life expectancy. These developments have led to a new era of research. New gene therapy drugs, new uses and dosages for current SMA drugs, and combination therapies with existing drugs are being developed and tested in clinical trials.

Aside from gene therapy drugs that either replace, activate, or modulate SMN genes, there are also new drugs and combinations in development that aim to protect motor neurons, enhance muscle mass, and improve neuron function.

Although researchers hope clinical trials will result in effective treatments, there’s no guarantee that a new treatment approach in a clinical trial will be beneficial. About 14 percent of medications in trials are ultimately approved by the FDA. Nonetheless, every SMA clinical trial provides critical data toward the development of future pediatric and adult treatments for SMA.

Read 5 Reasons To Consider Participating in SMA Clinical Trials.

Setting Up a Clinical Trial

Clinical trials are designed by research teams under the guidance of a principal investigator, the lead researcher, who is often a medical doctor. Clinical trial plans are carefully reviewed and regulated to protect the health and privacy of people who volunteer as participants. If laboratory research indicates a new drug, combinations, or dosage seems safe, researchers design clinical trial protocols, or a plan to begin research with human participants.

Every country has structures for reviewing and approving clinical trial protocols. In the U.S., the protocols for a clinical study must be reviewed by an ethics committee called an institutional review board and approved by the FDA before the clinical trial can begin.

Read Are Clinical Trials Safe for People With SMA?

Eligibility for Clinical Trials

Each clinical trial will have its own inclusion and exclusion criteria which make someone eligible to volunteer in the study. Eligibility for SMA clinical trials may include factors such as:

  • Current age
  • Age at SMA diagnosis
  • First symptoms of SMA
  • Genetic testing of SMN2 gene
  • Motor and respiratory function
  • Current treatment or past exposure to other drugs
  • Medical history and SMA type

Researchers may also consider your proximity to a clinical trial site, ability to commit to the time required for the clinical trial, or recent participation in other clinical trials.

A clinical trial may require you to stop your current treatment. If so, you would want to discuss this in detail with your doctor.

Informed Consent and Rights of Participants

Participating in clinical research is completely voluntary. Research teams are required to provide people with thorough information about a clinical trial, and opportunities to ask any questions before they agree to participate. This process is called informed consent.

Informed consent helps ensure participants are joining a research study with a full understanding of what will happen. There are three key aspects of informed consent:

  • Providing detailed information about the research, including potential benefits and risks
  • Facilitating understanding of the clinical trial, including giving potential volunteers time to review material on the research and discuss it with their doctor
  • Ensuring that potential participants know their rights and understand that enrollment is voluntary

Ask Questions

Be sure to ask important questions about the study. You can ask about the drug being studied, how it will be administered, and how your care will be managed during the clinical trial. In open label studies, you will know the name of a drug, but in some studies, the drug name is withheld. You may also want to ask if you will continue to have access to an investigational drug, dosage, or combination, if it works for you, once the study is complete.

It’s also important to know how much time is involved, where the trial will take place, and if you will incur any costs, including costs for travel. Health insurance companies usually cover at least some costs of a clinical trial. The sponsor of the trial, which may be a drug company, university, or organization that supports medical research, often covers additional costs.

Rights of Volunteers

Informed consent is designed to promote active and open communication between participants and researchers. Any participant in a clinical trial has the right to leave a study at any time, for any reason.

Privacy may also be a concern among clinical trial participants. Rules to protect personal health information are designed to allow researchers to share valuable data while protecting identifiable information about individuals in a study. In some cases, a clinical trial researcher may ask to share some aspects of your personal health information, which is something you would want to carefully consider before providing consent.

Clinical Trial Phases

There are four phases to a clinical trial. In each phase, a treatment is evaluated for safety and effectiveness. A clinical trial will advance to the next phase if approved by the FDA. At each new phase, more volunteers are usually recruited and testing becomes more rigorous. Any new treatment approach has a risk of side effects, which are closely monitored in clinical trials. If side effects are determined to be unsafe, a clinical trial will be suspended.

Phases for clinical studies of SMA drugs can have varying numbers of participants. Because SMA is a rare disease, clinical trials tend to include fewer people than more common medical conditions. SMA clinical trials typically follow this structure:

  • Phase 1 works with approximately 10 to 20 participants to test dosage and safety. Some or all volunteers would have SMA.
  • Phase 2 tests approximately 20 to 40 volunteers, all of whom have SMA.
  • Phase 3 tests a larger number of participants with SMA, which can range from 100 to 200 volunteers or more.

Testing in phase 3 of clinical trials is sometimes conducted as a randomized double-blind study with a control group. One group in the study would receive the investigational therapy. The control group in the same study may receive current, standard treatment or a placebo (a harmless, inactive treatment), which helps researchers better determine the effect of the drug under review. “Double-blind” means neither participants nor researchers know who is receiving the investigational therapy and who is not. This type of testing is designed to limit bias and produce more accurate outcome measures.

Therapies found to be safe and effective in phase 3 clinical studies are eligible for FDA approval for release and marketing to the public. As follow-up, phase 4 clinical trials continue to monitor usage of the therapy among larger populations.

Discuss Placebos With Your Doctor

If a placebo will be used in a clinical trial, you should be informed about the possibility of receiving it as part of informed consent. If you’re concerned about the chance of taking a placebo instead of treatment, discuss this issue with your doctor. People with SMA who participate in clinical studies often do so for potential for access to an investigational treatment, along with the desire to help others by contributing to SMA clinical research.

You can learn more about clinical trials at If you’re interested in taking part in a clinical trial, talk to your doctor about which clinical trials may be appropriate for you.

Talk With Others Who Understand

On mySMAteam, the social network for people with spinal muscular atrophy and their loved ones, more than 1,800 members come together to ask questions, give advice, and share their stories with others who understand life with SMA.

Do you have questions about clinical trials? Have you or a loved one participated in a clinical trial for SMA? Share your experiences in the comments below, or start a conversation by posting on your Activities page.

Posted on September 15, 2022
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Evelyn O. Berman, M.D. is a neurology and pediatric specialist and treats disorders of the brain in children. Review provided by VeriMed Healthcare Network. Learn more about her here
Joan Grossman is a freelance writer, filmmaker, and consultant based in Brooklyn, NY. Learn more about her here
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