The National Institutes of Health (NIH) has boosted funding for the first large-scale clinical trial aimed at identifying drugs to stop or slow Alzheimer's disease in people destined to get the debilitating illness.
The trial, led by Washington University School of Medicine in St. Louis, is known as the DIAN-TU trial, for the Dominantly Inherited Alzheimer's Network Trials Unit. The National Institute on Aging of the NIH has awarded $5.5 million in funding to continue and expand the trial, which is focused on dominantly inherited forms of Alzheimer's disease. In all, the National Institute on Aging will provide an estimated total of $26 million in funding over the next five years to support the groundbreaking trial.
With the new funding, patients enrolled in the trial can remain on the drugs they receive in the trial's initial stage, known as the biomarker testing phase, as the trial shifts to the final stage, known as the cognitive endpoint phase. The study is currently in the initial biomarker phase, which looks for early indications that the medication is having the desired effects in trial participants; in the cognitive endpoint phase, researchers will evaluate the drug's long-term ability to prevent or delay disease.
The last phase provides the critical data regulators such as the Food and Drug Administration consider when reviewing an investigational drug.
"This approach, called seamless adaptive trial design, enables us to condense the stages of the trial so it finishes three years earlier than the decade it normally would take," said principal investigator Randall Bateman, MD, of the School of Medicine. "Thanks to the support of this grant, the current DIAN-TU trial may lead to approved preventive treatments for dominantly inherited Alzheimer's disease."
The added support also will help the researchers enroll 300 to 400 additional participants in the trial and establish 10 to 15 additional sites for the study, which is treating volunteers in the United States, Canada, Australia and Europe.
Successful treatments for dominantly inherited Alzheimer's, a disease that typically strikes in a person's 30s, 40s, or 50s, one day may be used to slow or stop the much more common forms of Alzheimer's that occur later in life.
Nearly half of all late-onset Alzheimer's disease cases are linked to a particular form of one gene, Apoe4. But having one or two copies of this form doesn't guarantee a person will develop Alzheimer's.
In contrast, in dominantly inherited Alzheimer's, a single copy of one of the critical mutations, identifiable through genetic screening, means a person is almost certain to develop memory and other cognitive problems that may lead to Alzheimer's dementia.
Scientists have developed a detailed timeline of the brain changes Alzheimer's causes in the years before symptoms appear. The DIAN-TU trial is testing two treatments in patients with inherited Alzheimer's to see if the drugs can slow or stop the disease's progression and the onset of symptoms. DIAN-TU researchers continue to work with pharmaceutical companies to identify a third drug for testing in the trial.
Bateman, the Charles F. and Joanne Knight Distinguished Professor in Neurology, compares conventional clinical trials to putting people on a train that appears to be headed toward a desirable destination: successful treatment of a disease. As the train moves down the track and patients are treated with the trial drug, scientists check to make sure the train is still headed in the right direction.
Normally, the clinical trials process requires researchers to stop the train at some point, take all the passengers off and conduct a detailed assessment of their progress. (This is the end of what's known as a phase 2 clinical trial.)
To complete the journey to a new, approved treatment, researchers have to assemble a second, larger train (a phase 3 clinical trial), board the passengers and start that train moving. Building and starting a new train take a great deal of time and money.
"This new grant lets us keep the train rolling as long as it still seems to be moving toward the goal," Bateman said. "As long as we have a treatment that appears to be safely doing what it's designed to do, we can continue to treat and monitor DIAN-TU trial participants."
Regulators gave the DIAN-TU researchers the leeway to test new drugs in this fashion based in part on the urgent need for treatments for inherited Alzheimer's. The seamless process has been used before in investigations of potential treatments for cancer and heart disease, but the DIAN-TU trial is the first such trial for Alzheimer's disease.
As other Alzheimer's medications pass initial tests for safety and effectiveness, Bateman and his colleagues will consider evaluating them in the DIAN-TU trial. As in most late-phase clinical trials, the researchers will not know whether a study participant is receiving the drug or placebo. But independent monitors who are aware of this information will continue to watch the trial results for safety and effectiveness. The National Institute on Aging has supported the researchers since the 2012 launch of their investigation into dominantly inherited Alzheimer's disease.
"By providing us with this grant, the National Institute on Aging has made it possible for us to safely accelerate the journey toward a new era of preventive treatment for inherited Alzheimer's disease," Bateman said. "We can't say now if any of these new drugs will be successful, but we're looking forward to working at a faster pace with pharmaceutical companies and regulatory agencies to find effective treatments."
Additional supporters of the trial have included the Alzheimer's Association, which provided a $4.2 million grant, and pharmaceutical companies, which gave financial support and donated treatments. Private companies also donated a brain plaque imaging agent and a computerized cognitive skills test.
This research is supported by the National Institute on Aging of the National Institutes of Health (NIH), grant numbers R01 AG046179 and U01 AG042791. Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.