Rapid advances in our knowledge about AD have led to the development of many promising new drugs and treatment strategies. However, before these new strategies can be used in clinical practice, they must be shown to work in people. This means that clinical trials—and volunteer participants—are an essential part of AD research. Advances in prevention and treatment are possible thanks to volunteers who participate in clinical trials.
Clinical trials are the primary way that researchers find out if a promising treatment is safe. Clinical trials tell researchers which treatments are the most effective and for which people they may work best. Trials can take place in various settings, such as private research facilities, teaching hospitals, specialized AD research centers, and doctors’ offices. FDA approval is necessary before scientists can begin a clinical trial.
Participating in a clinical trial is a big step for anyone, including people with AD and their caregivers. That is why physicians and clinical trials staff spend time talking with participants about what it is like to be in a trial and the pros and cons of participating. It is also why they get a signed informed consent form before a person enrolls in a trial. Here are some facts that potential participants might want to know about clinical trials.
WHAT KIND OF TRIALS ARE THERE?
Treatment trials with existing drugs or behavioral strategies assess whether an intervention already approved for other purposes may be useful in treating age-related cognitive decline or AD. For example, trials have tested whether drugs used to lower cholesterol help slow progression of AD.
Treatment trials with experimental drugs or strategies show whether a new drug or treatment approach can help improve cognitive function or lessen symptoms in people with AD, slow the progression to AD, or prevent it. Interventions tested in these trials are developed from knowledge about the mechanisms involved in the AD process. Experimental drugs, for example, are first tested in tissue culture and in animals to determine their actions in the body. Safety and effectiveness studies are also conducted in animals before the compounds are tested in humans.
WHAT ARE THE PHASES OF CLINICAL TRIALS?
During Phase I trials, a research team gives the treatment to a small number of participants and examines its action in the body and its safety. The main goals of Phase I trials are to establish the highest dose of a new drug that people can tolerate and to define the dose at which people may begin to experience harmful side effects. These trials generally last only a few months.
If results show that the treatment appears to be safe, it will go on to Phase II and Phase III clinical trials. Phase II trials involve larger numbers of people studied over longer periods of time than Phase I trials. In these trials, the study team wants to know whether the treatment is safe and effective at changing the course of the disease. Phase II trials occasionally also involve the use of a placebo (an inactive substance that looks like the study drug). Results from Phase II trials give study staff an indication of the effective dose to take into Phase III trials. Phase III trials are large studies that compare an experimental treatment with a placebo or standard treatment to determine safety and efficacy (whether the treatment has the power to produce an effect).
After these phases are complete and investigators are satisfied that the treatment is safe and effective, the study team may submit its data to the FDA for approval. FDA experts review the data and decide whether to approve the drug or treatment for use in patients with the disease under study.
WHAT HAPPENS WHEN A PERSON SIGNS UP FOR A CLINICAL TRIAL?
First, it is important to learn about the trial. Staff at the clinical research center explain the trial in detail to potential participants and describe possible risks and benefits. Staff also talk about the participants’ rights as research volunteers, including their right to leave the trial at any time. Participants and their family members are entitled to have this information repeated and explained until they feel they understand the nature of the trial and any potential risks.
After all questions have been answered, participants who are still interested in joining the trial are asked to sign an informed consent form. In some cases, a participant may no longer be able to provide informed consent because of problems with memory and thinking. In such cases, it is still possible for an authorized representative (usually a family member) to give permission for the person to participate. Laws and regulations regarding informed consent differ across States and research institutions, but all are intended to ensure that participants are protected and well cared for.
Next, people go through a screening process to see if they qualify to participate in the trial. If they qualify and can safely participate, then they are enrolled in the trial.
WHAT HAPPENS DURING A TRIAL?
If participants agree to join the trial and an evaluation process shows they meet all the criteria for participation, then a “baseline” visit is scheduled with the trial staff. This visit generally involves cognitive and physical tests. This gives the team information against which to measure future mental and physical changes.
In most clinical trials, participants are randomly assigned to different study groups so that each study group has people in it of about the same average characteristics (such as age, sex, educational level, or cognitive ability). One group, the test group, receives the experimental drug or intervention. Other groups may receive a different drug, a placebo, or a different intervention. Comparing results for different groups gives researchers confidence that changes in the test group are the result of the experimental treatment and not some other factor, such as the placebo effect (this is when people feel an effect because they think they are getting the test medication even though they are really getting a placebo). In many trials, no one—not even the research team—knows who is getting the treatment and who is getting the placebo or other intervention. This means that the participant, family member, and the staff are “blind” to the treatment being received. This kind of trial is called a double-blind, placebo-controlled trial.
As the trial progresses, participants and family members usually must follow strict medication or treatment instructions and keep detailed records of symptoms. Every so often, participants visit the clinic or research center to have physical and cognitive exams, give blood and urine samples, and talk with trial staff. These visits allow the investigators to collect information on the effects of the test drug or treatment, see how the disease is progressing, and see how the participant and the caregiver are doing.
WHAT SHOULD PEOPLE CONSIDER BEFORE PARTICIPATING IN A CLINICAL TRIAL?
People who have participated in AD clinical trials say that it’s a good idea to consider the following issues before deciding to join a trial.
- Expectations and motivations. The test drug or treatment may relieve a symptom, change a clinical measurement, or reduce the risk of death, but clinical trials generally do not have miraculous results and participants may not receive any direct benefit. With a complex disease like AD, it is unlikely that one treatment will cure or prevent the disease. Some people choose not to participate or decide to drop out of a study because this reality does not meet their expectations. Others choose to stay in a trial because they realize that even if they get no or only a slight benefit, they are making a valuable contribution to knowledge that will help people in the future.
- Uncertainty. Some families have a hard time with the uncertainties of participation—for example, not knowing whether the person is taking the test treatment, a placebo, or a control treatment, not being able to choose which study group to be in, or not knowing for a long time whether the study was successful. Ongoing and open communication with study staff can help to reduce this frustration.
- Finding the right clinical trial. Some clinical trials involve participants who are cognitively healthy or have only mild symptoms because they are testing a drug that might delay a decline in cognitive function. Other trials involve participants who have more advanced AD because they are testing a treatment that might lessen behavioral symptoms. Or, a trial may be testing new strategies to help caregivers. Even if a participant is not eligible for one trial, another trial may be just right.
- The biggest benefit of all. Many families find that the biggest benefit of participating in a clinical trial is the regular contact with the study team. These visits provide an opportunity to get state-of-the-art AD care and to talk regularly with AD experts who have lots of practical experience and a broad perspective on the disease. The study team understands and can provide advice about the emotional and physical aspects of the person with AD and the caregivers’ experience. Team members can suggest ways to cope with the present and give insights into what to expect in the future. They also can share information about support groups and other helpful resources.
FOR MORE INFORMATION
To learn more about AD clinical trials, visit the Alzheimer’s Disease Education and Referral (ADEAR) Center’s Clinical Trials Database website (www.nia.nih.gov/alzheimers/clinical-trials ). This NIA website includes a list of AD and dementia clinical trials currently in progress at research centers throughout the United States. It also provides information about the phases of clinical trials and how to participate, explains the drug development process, and provides links to other useful websites. Also, visit the clinical trials websites of the National Institutes of Health (www.clinicaltrials.gov ) or the Alzheimer’s Association (www.alz.org ).