Long-awaited federal funding has been approved for a first-of-its-kind, Boston-led study to test whether drugs can hold off Alzheimer’s disease in people who have no symptoms of the illness, but who have an abnormal protein in their brains believed to be a hallmark of the disease.
The National Institutes of Health announced Monday that the clinical trial, to be led by Dr. Reisa Sperling, an Alzheimer’s specialist at Brigham and Women’s Hospital, is one of four that will be funded this year to find treatments for the disease
Sperling’s three-year study, which is the largest of the four, will receive the lion’s share of the money—roughly $36 million. The four trials will receive a total of $11 million this year, and could receive as much as $55 million combined over five years, the NIH said.
“I am very excited after all this time to really get started,” said Sperling, who has been planning this study for nearly two years.
Sperling’s trial will enroll 1,000 adults, aged 70 to 85, who have the abnormal proteins, known as amyloid plaques and revealed by brain scans, and who are exhibiting subtle cognitive problems that are typically reported in people years before they are diagnosed with Alzheimer’s.
The three-year study will give half of the participants a drug designed to clear amyloid plaques, and the others a placebo, and researchers will track the rate of cognitive decline in both groups.
Sperling said that if their hypothesis is right, the group that receives the amyloid-clearing medications will have a 25 to 35 percent slower rate of decline, compared with those who are receiving a placebo.
Other drug trials aimed at clearing the amyloid proteins in the brains of Alzheimer’s patients have produced disappointing or very modest results, with little or no apparent easing of symptoms, and researchers think that’s because the drugs were used too late.
So far no clinical trial testing anti-amyloid medications has proven successful in people with mild to moderate Alzheimer’s disease.
Scientists believe that more than 50 percent of certain critical brain cells are already lost by the time a patient displays even mild cognitive impairment. There is no known cure for Alzheimer’s disease.
“As a clinician, I am always upset when I talk about going earlier and earlier in the disease because it could seem to people that we are leaving a generation of people with dementia behind as we move earlier, and that’s not true,” Sperling said.
“This trial will ultimately impact people who don’t have symptoms,” she said. “It will help the children and grandchildren of people who suffer from dementia disease now.”
Sperling said her study will recruit volunteers from 50 sites across the country, including two in Boston—at the Brigham and likely at Boston University School of Medicine.
“There may be additional sites in Massachusetts,” Sperling said. “Some have contacted us in Western Massachusetts we may consider.”
Sperling said the researchers are still finalizing details, such as which medication they will study and the type of brain scanner they will use—decisions they expect to announce by the end of this week. The NIH money is just a piece of the needed funding, but she said they expect to hear soon on funding from industry and charitable foundations to finalize the support for the $140 million study.
The first participants are expected to be enrolled by the fall, but much work needs to be done before then, with final approval required by the US Food and Drug Administration.
“We believe we will need to screen 10,000 people,” Sperling said. “It’s a very hierarchal process, starting with phone screening, then questionnaires, then an in-clinic visit.”
Ultimately, Sperling estimates the researchers will perform brain scans on 3,000 of those 10,000 to select the final 1,000 in the study.
The three other NIH-funded studies include one that will test whether exercise—often widely recommended to maintain physical function and reduce age-related declines—is effective in slowing cognitive decline and brain atrophy in people with mild cognitive impairment, a condition that often leads to Alzheimer’s disease.
Exercise has not been shown in a longer-term clinical trial to improve cognition or alter the course of Alzheimer’s disease.
The year-long trial, led by researchers in North Carolina and California, will compare brain scans, cognitive testing, and spinal fluid from two groups of sedentary older volunteers, who already have some mild cognitive impairment, including one that will do high-intensity aerobic exercise, and the other that will do stretching.
All four studies are projects of a national consortium, known as the Alzheimer’s Disease Cooperative Study, which includes academic medical centers and clinics set up in 1991 to collaborate on Alzheimer’s treatments and research.