ADvance II Study Testing Deep Brain Stimulation in Mild Alzheimer’s Started, Enrollment Ongoing

The first patient enrolled in the ADvance II Study has been implanted with a deep brain stimulation (DBS) device to start treatment for mild Alzheimer’s disease.

The study will evaluate the safety and effectiveness of stimulating the fornix (DBS-f) — a major inflow and output pathway in the brain’s memory circuit.

The first participant was recruited by Anna Burke, MD, director of the Alzheimer’s and Memory Disorders Division at Barrow Neurological Institute, and by Francisco Ponce, MD, director of the Barrow Center for Neuromodulation.

The double-blind trial (NCT03622905) is currently recruiting up to 210 participants, ages 65 or older, across 14 sites in the U.S., Canada, and Germany.

Eligible patients should be in good general health and on a stable dose of Aricept (donepezil, by Pfizer and Eisai), Razadyne (galantamine, by Janssen), or Exelon (rivastigmine, by Novartis) for probable Alzheimer’s and mild dementia. Each participant also needs to have a reliable informant — usually a spouse, relative, or caregiver — who should be able to attend all study visits and report on the patient’s daily activities and function.

The study is expected to be completed by October 2024. For more information on participating, and on the study’s steps, visit its webpage here.

The trial was specifically designed to assess the safety and efficacy of DBS on the fornix (DBS-f), a brain area implicated in memory. All participants will have the DBS-f device implanted, but one-third — the “off” group — will only have it turned on after the 12-month visit.

“DBS-f delivers stimulation to a critical location in the brain’s memory circuit that seems to enhance activity in the circuit and drive neuronal activity in other brain regions impacted by Alzheimer’s,” Burke said in a press release.

Preclinical work in sheep and mice has suggested that targeting the fornix can improve memory and increase the activity of the hippocampus, a critical brain region for cognitive function.

The clinical trial, sponsored by Functional Neuromodulation, is using Boston Scientific’s Vercise directional DBS System, which was developed to increase the precision of electrical stimulation to the brain.

This system also is being used in people with Parkinson’s. DBS is a common approach for treating patients no longer responding effectively to medications. Epilepsy and essential tremor are two other neurological disorders also being treated with this technique.

ADvance II is based on findings of the previous ADvance study (NCT01608061), which demonstrated that DBS-f could benefit patients older than 65.

“The ADvance II study will enable us to assess whether stimulating the brain with DBS-f can drive neural activity in a way that might lead to better clinical outcomes,” Burke said.

In the U.S., the study will be conducted in Phoenix; Austin, Texas; Los Angeles; Stanford, Calif.; Baltimore; and Gainesville and Tampa, Fla. Other locations outside the U.S. include Toronto in Canada, and Cologne, Kiel, Würzburg, Magdeburg, Berlin, and Munich, all in Germany. Additional location details and contacts can be found here.

Alzheimer’s is the most common form of dementia, in which current pharmacological therapies show limited efficacy.

“There is an urgent need for new ways to treat Alzheimer’s,” said Todd Langevin, Functional Neuromodulation’s CEO.

“DBS is a promising alternative with a safe and successful track record in other neurological disorders.  Based on encouraging results from the feasibility trial, we have worked closely with a stellar group of scientific, clinical and regulatory experts to design ADvance II.”