Two new clinical trials funded largely by NIA—a major Alzheimer’s prevention study and a test of a promising insulin therapy in people with mild cognitive impairment or mild Alzheimer’s disease—are set to begin recruiting participants in early 2014.
The much-anticipated trials are being conducted by the Alzheimer's Therapeutic Research Institute  at the University of Southern California.
The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease Trial , or A4, is among a new generation of clinical trials being developed to test therapies that might prevent, or at least delay, Alzheimer’s disease in cognitively normal people at risk for the brain disorder. Previous trials have tested a variety of drugs in people who already had Alzheimer’s dementia, but results have shown no significant improvement in cognition or daily functioning.
Alzheimer’s-related brain changes are known to begin 10 to 20 years before symptoms of dementia appear. Researchers want to know if starting treatment earlier in the disease process—when people have these brain changes but no overt symptoms—will be effective. The A4 Trial is an attempt to find a long-sought disease-modifying treatment in people at this early stage.
“Testing an intervention presymptomatically, as early as possible in the development of Alzheimer’s, may be the best hope for keeping the disease at bay,” said NIA Director Dr. Richard J. Hodes.
The A4 Trial will test the drug solanezumab in 1,000 cognitively normal volunteers, age 65 to 85, who have enough of the amyloid protein in the brain to put them at risk for developing Alzheimer’s. The presence of plaques made of amyloid fragments in the brain is a key feature of Alzheimer’s disease. However, not all people with amyloid in the brain progress to dementia.
Dr. Reisa Sperling
Phase III clinical trials sponsored by Eli Lilly and Co. have shown that solanezumab helped clear amyloid from the human brain. In addition, it slowed cognitive decline in people with mild Alzheimer’s, but it did it not help those at a more advanced stage.
To qualify for the upcoming A4 Trial, volunteers will undergo a positron emission tomography (PET) brain scan to see if they have abnormal levels of amyloid. A group of 500 volunteers without Alzheimer’s-related brain changes will also be part of the study. Participants at about 60 study sites across the United States will be randomly assigned to take either solanezumab or a placebo (inactive drug) for 3 years. Solanezumab is a monoclonal antibody given by intravenous infusion.
Researchers led by Principal Investigator Dr. Reisa Sperling, of Harvard Medical School, Boston, will determine if and how the drug affects A4 participants’ pace of cognitive decline by conducting tests of memory and other thinking abilities. They will also use imaging tests to track changes in brain structure and function.
People interested in participating in the A4 Trial can e-mail A4firstname.lastname@example.org  to be notified when the trial opens for enrollment.
Another ADCS study, Study of Nasal Insulin to Fight Forgetfulness  (SNIFF), will test an insulin nasal spray to see if it improves or preserves memory in adults with memory-related mild cognitive impairment or mild Alzheimer’s disease. A total of 240 adults, age 55 to 85, will participate in the trial at 29 research clinics nationwide. Participants must not have diabetes or be taking diabetes drugs.
“Results of previous smaller trials suggest that intranasal insulin delays memory loss and preserves functional ability in adults in the early stages of Alzheimer’s dementia,” said Dr. Laurie Ryan, chief of the Dementias of Aging branch of NIA’s Division of Neuroscience. “The SNIFF trial will advance that research by testing the therapy in a larger group of volunteers treated for a longer period of time.”
Insulin, a hormone often used to treat diabetes, is thought to carry out multiple functions in the brain, and poor insulin regulation may contribute to the development of Alzheimer’s. Insulin resistance, reduced insulin levels in cerebrospinal fluid, and lower insulin brain signals in people with Alzheimer’s suggest that a therapy aimed at these problems may help.
Dr. Suzanne Craft
SNIFF participants will be randomly assigned to take insulin or a placebo twice a day for 1 year, using a device that delivers insulin directly from the nose to the brain. They will also undergo magnetic resonance imaging (MRI) brain scans and lumbar punctures (to gather cerebrospinal fluid samples) to help researchers learn more about how insulin works in the brain and affects brain structure and function. Participants will take memory and other tests to see if their cognition and daily functioning improve after treatment. After 1 year, all participants will receive insulin therapy for 6 months to help investigators obtain more safety data.
Researchers led by Principal Investigator Dr. Suzanne Craft, of the Wake Forest School of Medicine, Winston-Salem, NC, will also assess whether gender, genetic status, and biomarker measures can predict how participants respond to insulin treatment.
For detailed eligibility criteria and other information about SNIFF, visit the ADCS website .