NGF Blog


Clinical Trials & Gaucher Disease: Phases, Types, & What You Should Know

Medical research has always been important for furthering our understanding of disease. Through the completion of clinical studies, doctors and scientists identify new and effective treatment methods for some of the rarest diseases, including Gaucher disease.

Gaucher Disease Clinical Trials

The mainstay of Gaucher disease treatment—enzyme replacement therapy (ERT)—was developed thanks to clinical trials. More recently, trials involving substrate reduction therapy explored the use of these oral medications in the management of type 3 Gaucher disease.

Without these structured and highly regulated studies, treatment advancements are simply not possible. After many years of wishful thinking, the dawn of gene modification treatments for hereditary diseases such as Gaucher disease is finally here. Soon patients likely will be asked to consider enrolling in gene therapy clinical trials for Gaucher disease. It is important that patients and families have sufficient information to decide whether participation in such trials is right for them.

Dr. Neal Weinreb, Voluntary Associate Professor of Clinical Genetics and Medicine (Hematology) at the University of Miami Miller School of Medicine and NGF Medical Advisory Board member, notes that people living with Gaucher disease have good reason to be interested in these as well as other clinical trials aimed at broadening knowledge and improving available treatment options. “These trials may help develop new medications, or they may study current medications being used for new purposes. Other studies may look at biomarkers in blood, or they may evaluate new imaging techniques. You can have clinical trials involving almost every aspect of medical care.” 

What is a Clinical Trial?

Clinical trials are research studies involving humans. These studies evaluate behavioral, medical, or surgical interventions for a variety of diseases and medical conditions. In most cases, the end goal of clinical research studies in the United States is to receive U.S. Food and Drug Administration (FDA) approval for the new intervention. This eventually allows a drug company or other trial sponsor to bring their product or technique to market.

How do clinical trials work?

Researchers design each clinical trial in accordance with a comprehensive set of rules and regulations, all intended to protect patient privacy and safety. Trials always include sponsors and primary investigators who oversee the trial.

The first, and perhaps most obvious, step is identifying a testable hypothesis; that is, what question is the clinical trial trying to answer? Once investigators write the hypothesis, they must then write a protocol for the study. “Protocols are like recipes. They provide detailed information about each step of the clinical trial. Protocols present the investigators’ rationale for completing the research and may also offer preclinical evidence for the new treatment, like information gathered during laboratory or animal testing,” says Dr. Weinreb.

Protocols also specify other types of information, such as:

  • The anticipated length of the trial
  • What tests are used to confirm results, such as laboratory or imaging tests
  • Whether tests are completed using adult or pediatric patients
  • Which patients are eligible to participate in the trial
  • Who receives placebos instead of the trial treatment

Investigators identify specific end points to the trial, or data used to determine whether a new therapy is effective. “In earlier clinical trials involving patients with Gaucher disease, investigators looked at hemoglobin levels after a year of treatment. This helped determine whether early treatments were effective. Now, researchers usually look at reduction in spleen size as the primary end point for evaluating effectiveness of new treatments,” says Dr. Weinreb.

Most clinical trials incorporate a concept known as randomization when selecting patients. This means investigators recruit a large pool of patients for whom they know their age, sex, medical history, and other information. Researchers then randomize patients into at least two groups. A test group of patients receives the new therapy. Others remain in a control group, receiving no care or care according to current treatment standards.

In most cases, patient recruitment takes place on a site-by-site basis. But some organizations, such as NGF, help by publishing current research protocols specific to people living with Gaucher disease. These protocols include contact information so that any interested individuals can contact the investigators directly. 

Phases of Clinical Trials

The clinical trial process is made up of four distinct phases:

  • Phase I: A small group of people, usually 20 to 80, receives an experimental treatment to determine its safety and side effects. Phase I trials help researchers determine information such as correct drug dosages. In the case of rare diseases, it is often difficult to recruit so many patients; instead, the trial design must be constructed to accommodate smaller numbers of trial subjects. The clinical trial that resulted in approval of the first treatment for GD, alglucerase (Ceredase) enrolled only 12 patients.
  • Phase II: 100 to 300 people enroll in phase II trials, helping investigators determine whether the new treatment is actually effective.
  • Phase III: Several hundred to as many as 3,000 people participate in phase III trials, which gather more information about a new treatment’s safety and effectiveness. If a new drug or therapy creates positive results, the FDA will likely approve the new intervention.
  • Phase IV: After the FDA approves a new drug or device, it’s continuously monitored in large, diverse populations. This process helps identify safety issues or side effects which may not emerge until years after the initial treatment. Databases like the International Collaborative Gaucher Group (ICGG) Gaucher Registry store information about diseases and their treatments. The ICGG Gaucher Registry helps experts conduct better research using up-to-date information from people living with Gaucher disease.

Types of Clinical Studies

Generally, people may participate in one of three types of studies:

  • Cross-sectional studies: This type of trial examines a cross section of patients in a single moment in time. Doctors often use cross-sectional studies to determine how many people with a certain disease may have specific laboratory test abnormalities. For example, cross-sectional studies may be used to show how many patients with Gaucher disease are anemic before starting treatment).
  • Longitudinal studies: Longitudinal clinical trials follow patients over a set time period. Most new drug trials are longitudinal.
  • Observational studies: Researchers observe patients in their normal settings to help identify possible hypotheses for clinical trials.

Another type of study, known as a natural history study, helps researchers collect data to better understand how specific diseases progress without intervention. For Gaucher disease, patient registries may help complete this process. “This information helps show whether certain medications are breakthrough treatments. After all, this is how ERT first got approved. Doctors knew–based on natural history studies—that the enlarged spleen in patients with Gaucher disease very rarely spontaneously decreased in size. On the other hand, every patient treated with Ceredase had a reduction in spleen size. Even without a control group, the evidence was so compelling that the drug was approved,” says Dr. Weinreb.

Protecting Clinical Trial Patients

Clinical research studies guarantee special patient privacy protections, in addition to those provided by the Health Insurance Portability and Accountability Act (HIPAA) of 1996. Researchers “de-identify” data during its collection and storage. Dr. Weinreb says, “People usually receive some type of trial number for identification. Investigators now usually code patients by randomly generated numbers. Only the principal site investigators have access to a patient’s personal health information. This makes it much harder for other study personnel to identify specific people.”

Collecting Research Information

Usually, researchers collect data about individual patients while they’re on-site. In some cases, patients enter data into computers themselves. Throughout the process, a data safety committee monitors the results. These independent experts identify serious issues or adverse events affecting the research. In some cases, they may recommend stopping the trial completely.

The IRB’s Role in Clinical Research

In the past, medical research wasn’t as regulated as it is today. As a result, some patients participated in trials without sufficient information to understand the risks. Others had their personal medical information compromised. Some even suffered real harm or injury. Institutional Review Boards (IRBs) now help prevent these problems from occurring.

IRBs review, approve or modify, and monitor virtually every clinical trial. Physicians, scientists, bioethicists, and representatives from the community all participate in IRB functions. Before a trial begins, the IRB reviews the protocol to ensure the investigators conduct research with scientific and ethical integrity. This review also ensures the trial meets certain criteria, including that patients have given informed consent.

Informed consent is fundamental to the success of clinical trials. In all cases, trial investigators must:

  • Ensure each patient understands any and all relevant medical information related to the trial
  • Present information accurately and sensitively to each patient
  • Document informed consent in the patient’s medical record

After the trial begins, the IRB works with investigators to continuously update them on the legalities and ethics of the situation to help protect patients. Most universities have their own IRBs, but there is currently a growing number of central IRBs. These national boards are particularly useful when clinical trials occur at several different study sites.

Pros and Cons of Clinical Trials

Clinical trials present exciting opportunities to try innovative new medical therapies. But before deciding to participate, people must weigh the benefits and risks of clinical trials. “It can be particularly tricky to say whether someone should enroll in a clinical trial. It really depends on several factors, such as the nature and severity of the disease in question. Also, participation may depend on whether a patient has other medical conditions, or whether there are documented unexpected side effects,” says Dr. Weinreb.

“There’s a reasonable expectation that the trial will find interventions that are beneficial to the patient, but we can’t say this with absolute certainty. Giving each patient as much information as possible helps them decide whether clinical trials are right for them,” notes Dr. Weinreb.

Considerations for Gaucher Disease Gene Therapy

“We all recognize there are effective treatments for Gaucher disease now that help people live a normal, functional life. Therefore, people with Gaucher disease should ask themselves: is this new treatment going to be at least as good as the treatment they currently receive? It may take some serious reflection to arrive at any decisions,” says Dr. Weinreb.

People living with type I Gaucher disease in particular must weigh the risks and benefits of clinical trials, since modern treatments like ERT are already very effective. As prospective treatments emerge, such as gene therapy, it may take some thought to determine whether participation is a good idea. “With issues like gene therapy, we just don’t know how the Gaucher disease population could be affected. Will this be a one-time treatment? What are the risks of gene therapy for someone with Gaucher disease? Will gene therapy cause any damage later in life? These are all important questions prospective patients must ask themselves to stay as healthy as possible,” says Dr. Weinreb.


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