The five-year APOE4 trial will involve more than 1,300 cognitively healthy older adults, ages 60 to 75, at high risk of developing symptoms of Alzheimer’s because they inherited two copies of the apolipoprotein E (APOE4) gene — one from each parent. About 2 percent of the world’s population carries two copies of this gene and one in four people carry one copy of the APOE4 gene, which is strongly linked to late-onset Alzheimer’s.
"We are taking clinical trials to a critical new stage," said Dr. Pierre N. Tariot, study director for BAI, an arm of Banner Health, one of the largest nonprofit healthcare systems in the United States. "This approach shifts the research paradigm from trying to reverse disease damage to attacking and preventing its cause, years before symptoms could surface."
The trial — subject to regulatory authority approval — will begin in 2015 at approximately 60 sites in Europe and North America, including BAI’s headquarters in Phoenix, Ariz.
The active immunotherapy is aimed at triggering the body’s immune system to produce antibodies that attack different forms of the amyloid protein, which many researchers have suggested plays a critical role in the development of Alzheimer’s. The oral medication is a BACE (beta-secretase1) inhibitor, designed to prevent the production of different forms of the amyloid protein.
The two drugs, which will be tested separately, are intended to stop the accumulation of amyloid. The drugs are being introduced even before amyloid accumulates in some of the participants’ brains. The trial will increase the chance of finding treatments that will prevent, slow or delay the loss of memory and other cognitive abilities associated with Alzheimer’s.
Study participants will be recruited via multiple venues, including the Alzheimer’s Prevention Registry website created by BAI in 2012. The registry (www.endALZnow.org) currently has more than 37,000 potential volunteers and is aiming to recruit more than 250,000.
Volunteers who meet the study criteria will be asked to mail a sample of their genetic material (such as a cheek swab) to a laboratory. The volunteers will learn the results of that test in the context of possibly enrolling in the trial.
Volunteers who are selected for the API APOE4 study will receive genetic counseling. "We are keenly aware of the extreme sensitivity and emotional impact of disclosing genetic information," Dr. Langbaum said.
"There are no guarantees that any of these investigational treatments will prevent the clinical onset of Alzheimer’s disease," said Dr. Eric M. Reiman, one of the study directors for BAI. "But we are grateful for these opportunities to find out."