Clinical Trials 101: Your Guide to Ankylosing Spondylitis and Research

Current research is focused on several areas to better understand what causes ankylosing spondylitis and how to treat it. Genetic markers Research has demonstrated that there are genetic factors that play a role in the development of AS. Having family members with the disease increases your risk of developing it, and research suggests that over 90% of the risk of AS relies on a person’s genes. One of the most well-known genetic markers is HLA-B27. However, HLA-B27 only accounts for about 20% of the genetic risk. Other genetic factors that have been identified include ERAP 1, IL-12, IL-17, and IL-23.1,2 One gene – TLR7 – seems to be a marker for susceptibility in males but has a protective effect in females.1 More research is needed to understand all the genetic factors and how they react to different environmental factors. The microbiome The microbiome is the collection of different microorganisms, like bacteria, fungi, and viruses, that are naturally a part of the human body. The microbiome plays many important roles, including the function of the immune system. Alterations in the microbiome can lead to dysfunction in the immune system and have been linked to several autoimmune diseases.3 An estimated 70% of people with AS have inflammation in the gut, which may be related to a dysbiosis (imbalance) in the gut microbiome. Researchers have demonstrated that the gut microbiome is altered in people with AS, and this imbalance in the microbiome may be actively involved in the disease process of AS.4 It is not yet known whether certain genetic factors influence the microbiome, or whether changes to the microbiome, such as due to an infection, trigger other processes that lead to the development of AS.1 The microbiome continues to be an area of research, as scientists uncover which microorganisms are critical for health and how best to rebalance a microbiome that is altered. New treatments There are several new treatments under investigation for AS. Some of these new treatments may be available to certain patients through clinical trials. Clinical trials are a type of medical research in which new treatments are studied in groups of patients. Through the clinical trial process, new treatments can be tested to find more effective treatments. Interleukin inhibitors One of the types of biologic treatments that are under investigation for AS are interleukin inhibitors. Interleukins (IL) are chemical messengers that are involved in the inflammatory process in the body. People with inflammatory arthritis conditions like AS have abnormally high levels of some of these interleukins, and certain biologics can block specific interleukins. Several of these IL therapies are currently in clinical trials for various inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, and AS.1 JAK inhibitors Janus kinases (JAKs) are a group of enzymes that work within the immune system and other cells to transmit signals that influence certain cell functions, including promoting inflammation. JAK inhibitors block these enzymes and are currently approved for other inflammatory conditions like rheumatoid arthritis. JAK inhibitors are being studied in people with AS to see if they help with the inflammation and other symptoms of AS.1 Biosimilars Biosimilars are a type of biologic therapy that are highly similar to an already approved biological product. While they are not generic versions of the approved products, they do provide another option and may be less expensive to patients. Several biosimilars are already available for the treatment of AS and more are being developed and investigated. Stem cells Stem cells are immature cells that can develop into other cells in the body. While they are well-known as being present in embryonic tissue, stem cells are also present in adult bodies. While current biologic treatments target the inflammatory processes that occur in AS, these therapies do not affect the abnormal bone formation and damage that occurs. Researchers are investigating whether stem cell transplants may offer a way to regenerate healthy bone tissue in people with AS. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site" title="Sign up for emails from {{site-name}}:”] A clinical trial is a research study that is conducted to determine whether a specific medical intervention, such as a treatment, device, procedure, or change in behavior is safe and effective in humans.1,2 A clinical trial may be designed to compare a new treatment to one that is already available, to a placebo (contains no active ingredients), or to no intervention. Further, some clinical trials compare interventions that are already available to each other. The process of investigating the safety and efficacy of a specific intervention is complex, and clinical trials are actually one of the final stages of that investigation. A new intervention will first be examined in a laboratory, and if data for that intervention look promising, the next step could involve testing that intervention on animals. Of course, even if that intervention seems promising in animals, it may or may not have similar results in humans. Therefore, testing a new intervention in humans is necessary. This testing is done in multiple phases, which are defined by the Food and Drug Administration (FDA). Clinical trial phases Phase 0 The Phase 0 study is a relatively new designation. They are exploratory in nature and involve very limited human exposure to the drug. They are also known as human microdosing studies, with a goal of speeding up the process of development for promising drugs by examining the pharmacokinetics of the drug in a very small number of patients (10-15). Phase 1 Phase 1 studies are usually conducted with a small group of healthy volunteers (usually between 20-100 people) and examine safety of the drug. The goal is to evaluate the drug’s most frequent and serious adverse events. Often times a secondary goal will be to look at how the body processes the drug (metabolism and secretion). Phase 2 Phase 2 studies gather preliminary data on the efficacy of a drug in people who have a certain disease or condition, and these studies include a larger number of patients (typically 100-300). Study participants receiving the drug may be compared with similar participants receiving a different treatment, which is usually an inactive substance (called a placebo) or a different drug. The safety of the new drug continues to be examined. Phase 3 Phase 3 studies gather more information about safety and effectiveness of a drug. Phase 3 studies include a much larger group of participants (often 1000-2000), with the goal of definitively assessing how efficacious a treatment is. It is typical for there be at least two successful Phase 3 trials that demonstrate the safety and efficacy of a drug to gain approval from the FDA. Phase 4 Phase 4 studies are conducted after FDA has approved a drug for marketing. These studies gather additional information about a drug’s safety, efficacy, or optimal use. Funding for clinical trials Clinical studies can be funded by a variety of sources, including pharmaceutical companies, academic medical centers, voluntary groups, federal agencies such as the National Institutes of Health, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. Physicians, health care providers, and other individuals can also sponsor clinical research. Clinical trial locations Clinical trials take place in a variety of settings, including hospitals, doctors’ offices, universities, and community clinics. Often times, a clinical trial will have multiple sites. This is determined by who is conducting the trial. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site" title="Sign up for emails from {{site-name}}:”] There are several terms that are commonly used when discussing clinical trials. Here are some that come up often: Adverse event: an undesirable experience associated with the use of a medical product in a participant. Arm: a grouping of study participants who receive a specific intervention, or no intervention, according to the study protocol. Baseline characteristics: data collected at the beginning of the study for each participant, including demographics like age, gender, and race. Data for study-specific characteristics like prior treatment, weight, etc., will also be collected. ClinicalTrials.gov identifier (NCT number): the unique identification code assigned to each clinical trial that is registered on ClinicalTrials.gov. Controlled trial: A type of clinical trial that examines an intervention compared with a standard (called the control). Double blind trial: A clinical trial where at least 2 parties involved, usually the patient and the investigator, do not know what intervention the patient is receiving. This is to avoid potential bias. Exclusion criteria: Factors that would prevent a person from participating in a study. FDA: Food and Drug Administration.1 Inclusion criteria: Factors that allow a person to participate in a study. Intervention: The focus of the clinical study. This could be a drug, a medical device, a medical procedure, other investigational products, as well as surveys, education, or interviews. Investigator: A person who is conducting research of a clinical study. Open label: A term describing a clinical trial where blinding is not used. All parties involved know which study participants have been assigned to which interventions. Outcome measure: A measurement that is outlined in the study protocol that is used to determine the effect of the intervention. Placebo: A substance that does not contain active ingredients and is designed to appear the same as the intervention being examined. Primary outcome measure: The main outcome measure that is evaluating the effect of the study intervention. Making decisions can be tough, especially when they relate to your health! One decision you may face is whether or not participating in a clinical trial is right for you. There are several types of clinical trials, and each have different goals and requirements. So, while one clinical trial may not be a good fit for you, there may be others that are. If you’re thinking about exploring clinical trial options but still aren’t sure, ask yourself some questions to determine if a clinical trial might be right for you: Am I willing to work with a new healthcare team during the trial? While you can still see your doctor while enrolled in a clinical trial, you will also be seeing a new group of healthcare professionals who are working on the study. Clinical trials are conducted by a group of researchers. The lead researcher for a trial is called the principal investigator (PI), who is usually a medical doctor or other healthcare professional. The research team may also include other doctors, nurses, and researchers. This research team is usually different from the healthcare team you see for your regular care. It’s important to inform your usual healthcare team of the clinical trial you are thinking of participating in and to discuss how the process will work. Am I willing to follow the trial protocol? The clinical trial protocol is a detailed plan of what the trial will involve. When you agree to participate in a clinical trial you will sign an informed consent document, which outlines the protocol and any tests, procedures, or appointments that are expected of you. These expectations may impact your day-to-day life. When reviewing the trial protocol be sure to note when you will need to travel to appointments and how often you may be required to have tests or procedures, like blood draws or MRI scans. You may also be asked to stop taking medications you are currently on while you are in the clinical trial. Keep an up-to-date list of all medications, including over the counter medications, and show this to the clinical trial team to be sure you can continue taking them during the trial. Am I okay with potential unknowns? Some clinical trials are blinded, or masked, meaning that participants will not know what medication they are receiving. Some studies are double-blind studies, meaning both the participant and the research staff will not know what medications a participant is on. This is done to prevent any bias or influence and to allow the participant and researchers to measure the true effect of a drug. In blinded trials, you will be informed of all possible treatments that will be part of the trial, including no treatment (placebo). Before agreeing to participate, it is important to ask yourself if you would be okay with receiving any of the possible treatments, and if you could handle not knowing which treatment you may be given. Am I okay with the possible risks? The research protocol and informed consent document will outline your rights as a clinical trial participant. This document will note the potential benefits for participating in a clinical trial and will also note potential risks. Clinical research is approved and monitored by an Institutional Review Board (IRB) that ensures any risks are minimal. While the research team and IRB will do everything possible to minimize risks, it cannot always be guaranteed. It is important to take note of the potential risks you may incur and decide if these possible risks are worth the benefits. Will I be okay with the possibility of not being selected? Clinical trials are designed with certain criteria and researchers are often looking for a select group of participants with certain medical histories. These characteristics and medical histories are outlined in the trial’s inclusion and exclusion criteria. One of the main reasons people are excluded from a study is to maintain their safety. For some clinical trials, you may agree to participate and sign an informed consent document, but then be found to be ineligible for the trial after further testing. If you are not selected for a particular trial this does not mean that you cannot try and enroll for a different clinical trial. There may be other questions you have about clinical trials. You may want to talk with friends, family, and your doctor, or ask the community for their experience. Ultimately, it’s important you make a decision that you feel comfortable with. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site" title="Sign up for emails from {{site-name}}:"]

Clinical Trials 101: Your Guide to Ankylosing Spondylitis and Research

Investigational Therapies and Research for Ankylosing Spondylitis

Understanding Clinical Trials

Clinical Trial Terminology

10 Things You Should Know About Clinical Trials

Is a Clinical Trial Right for Me? 5 Questions to Help you Decide

The Clinical Trial Consent Form: Understanding Your Rights & Responsibilities

Not Always a Placebo! Types of Clinical Trials

Clinical Trials as a Treatment Option

Why Wasn’t I Chosen for a Clinical Trial?

Clinical Trial Participation