With new research funding from the National Institutes of Health (NIH), the nation’s premier Alzheimer’s disease study network will be undertaking four major studies which are aimed at finding new treatments for the disease.
The National Institute on Aging (NIA), the lead institute within NIH for Alzheimer’s research, announced the award on Jan. 14, 2013. The ADCS will receive $11 million in fiscal year 2013, and the effort could total as much as $55 million over the five years of the project.
The award supports the latest projects of the Alzheimer’s Disease Cooperative Study (ADCS), a national consortium of academic medical centers and clinics set up by NIH in 1991 to collaborate on the development of Alzheimer’s treatments and diagnostic tools. In this round of studies, the ADCS will test drug and exercise interventions in people in the early stages of the disease, examine a medication to reduce agitation in people with Alzheimer’s dementia, and test a cutting-edge approach to speed testing of drugs in clinical trials.
The consortium, coordinated by the University of California, San Diego and led by Paul Aisen, MD, is made up of more than 70 research sites in the United States and Canada with a focus on advancing studies of interventions that might not otherwise be tested by industry.
“The ADCS is a key initiative in the federal program to discover, develop and test new Alzheimer’s treatments and diagnostic tools. Over the years, it has proved invaluable in advancing our understanding about the disease and how to conduct research in this challenging area,” said NIA Director Richard J Hodes, MD. “I am particularly excited that this round of studies will use what we have learned by testing interventions pre-symptomatically, as early as we can in the development of the disease, where we now think the best hope lies for keeping Alzheimer’s at bay.”
The ADCS and this latest round of studies, Hodes noted, are critical to accomplishing the research goals set forth in the National Plan to Address Alzheimer’s Disease announced by Health and Human Services Secretary Kathleen Sebelius in May 2012. The plan was developed under the National Alzheimer’s Project Act [PDF] , which calls for a coordinated and concentrated effort in research, care and services for Alzheimer’s and related dementias. Its primary research goal is to prevent and effectively treat Alzheimer’s disease by 2025.
The four studies made possible under the new award are:
The A4 Trial — The development of plaques made up of amyloid protein fragments is a key feature of Alzheimer’s disease. So far, no clinical trial testing anti-amyloid agents has proven successful in people with mild to moderate Alzheimer’s dementia. Because Alzheimer’s-related brain changes take place years, even decades, before symptoms appear, scientists are now aiming to test therapies earlier in the disease process. The A4 (Anti-amyloid treatment in asymptomatic Alzheimer’s disease) secondary prevention trial will test an amyloid-clearing drug in the pre-symptomatic stage of the disease, in 1,000 symptom-free older volunteers who have had positron emission tomography brain images that show abnormal levels of amyloid accumulation. Cognitive tests over three years are designed to determine if the drug is effective in maintaining cognitive health, and imaging tests will track structural and functional brain changes. The trial, which will also be supported by private sector contributions, will provide important information about the effectiveness of clearing amyloid from the brain in the early stages of the disease and inform future prevention studies. (Principal investigator: Reisa Sperling, M.D., Harvard Medical School, Boston.)
Exercise MCI Trial — Although exercise is widely recommended to maintain physical function and reduce risk of a number of age-related medical conditions like cardiovascular disease and diabetes, it has not been shown in a longer-term clinical trial to improve cognition or alter the hallmarks in the brain of Alzheimer's disease. This randomized, controlled trial seeks to find out if supervised aerobic exercise can influence cognitive decline, slow brain atrophy, or mitigate Alzheimer’s pathology in older adults with mild cognitive impairment (MCI), a condition that often leads to Alzheimer’s disease. The trial will recruit sedentary older volunteers with MCI to participate in a year-long program in which one group will do high-intensity aerobic exercise and the other stretching. Cognitive testing, cerebrospinal fluid biomarkers and magnetic resonance imaging results will provide critical data on the efficacy of aerobic exercise on improving cognition and Alzheimer’s-related pathology. (Principal investigators: Laura D. Baker, Ph.D.,Wake Forest School of Medicine, Winston-Salem, N.C. and Carl Cotman, Ph.D., University of California, Irvine.)
Prazosin for Treating Agitation Trial — Disruptive agitation is often a chronic problem in people with Alzheimer's, dramatically increasing caregiver burden and patient distress, often leading to long-term care outside the home. Currently, drugs used to treat agitation are not very effective and may even cause additional harm in older people, such as increased risk of stroke or excessive sedation. The ADCS will test the use of the generic drug prazosin as a treatment for agitation that may also be well-tolerated in frail and elderly people. (Principal investigator: Elaine Peskind, M.D., University of Washington Alzheimer’s Disease Research Center, Seattle.)
CSF Pharmacodynamic Trial — When testing potential new drug therapies, specifically ones that target key Alzheimer’s disease pathways, scientists use cerebrospinal fluid and blood plasma biomarkers as a way of knowing that the compound crossed the blood-brain barrier and engaged the relevant target. Additionally, these biomarkers help track the relationship between blood levels and central nervous system effects. To increase the efficacy and speed of drug development, the ADCS will employ advanced methods that sample cerebrospinal fluid and plasma levels over time. These methods will track levels of several Alzheimer's-related proteins to help researchers better understand how a drug influences Alzheimer’s pathology and to help guide decisions on whether a drug warrants further clinical testing. (Principal investigators: Douglas R. Galasko, M.D., University of California, San Diego and Martin Farlow, M.D., Indiana University Alzheimer’s Disease Center, Indianapolis.)
"The ADCS has long benefited the wider research community by emphasizing the importance of collaboration and data-sharing and by focusing on trial design and instrument standardization," said Laurie Ryan, Ph.D., NIA Alzheimer's disease clinical trials program director. "With this newly funded work, the goal is to expand the range of individuals participating in ADCS clinical trials from those at risk for the disorder to those with Alzheimer's dementia, so that the full spectrum of the disease is represented."
The NIA launched the ADCS in 1991 under a cooperative agreement, in which NIH participates in the management of the studies. Over the past two decades, the ADCS has built an infrastructure emphasizing collaboration and data sharing. It focuses on evaluating interventions that will benefit Alzheimer’s patients across the disease spectrum. This includes testing agents that lack patent protection; agents under patent protection that are already marketed for other uses but which might prove useful in treating Alzheimer's; and novel compounds developed by individuals, academia, pharmaceutical companies and small biotech companies.
In addition to testing new therapies, the ADCS mission includes the design of new instruments for use in clinical studies and the development of novel and innovative approaches to Alzheimer's disease clinical trial design and analysis. The ADCS also strives to enhance the recruitment of minority groups into Alzheimer's studies. To date, the ADCS has conducted 30 studies (23 drug studies and seven instrument development protocols).