Deep brain stimulation for treatment of severe Alzheimer's disease: Study protocol for a prospective, self-controlled, phase I trial (case observation)

Background: With the aging of the global population, an increasing number of people are at risk of developing Alzheimer's disease. There is currently no effective treatment to hinder or postpone the progression of Alzheimer's disease. Cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist Memantine are the commonly prescribed drugs for this disease, but their therapeutic effects are still unsatisfactory. Therefore, there is an urgent need to investigate novel treatment methods. Many animal experiments have suggested that deep brain stimulation benefits Alzheimer's disease, but clinical trials investigating this are still in their infancy. This study aims to investigate the safety and effectiveness of deep brain stimulation in the treatment of severe Alzheimer's disease. Methods/Design: This study is a prospective, self-controlled, phase I trial (case observation), which will be performed in the Department of Neurosurgery, Chinese PLA General Hospital (Beijing, China). Six patients with severe Alzheimer's disease will be enrolled to receive continuous bilateral deep brain stimulation of the fornix. Evaluations will be performed at baseline (prior to surgery) and at 1, 6, and 12 months after surgery. The primary outcome measures are disability and mortality rates during the 12-month deep brain stimulation trial period. Secondary outcome measures include the incidence of complications and Clinical Dementia Rating scale, Zarit Caregiver Burden Interview, Mini-Mental State Examination, and Barthel Index of Activities of Daily Living Scale scores. Patient recruitment will begin in August 2017, the analysis of primary outcome measures will be completed in October 2018, and the study will finish in June 2019. Discussion: The results of this study will help to determine the safety of deep brain stimulation for the treatment of severe Alzheimer's disease. We will also assess whether deep brain stimulation can improve the cognition, symptoms, and activities of daily living of patients with Alzheimer's disease. If the study succeeds, a novel option for patients with Alzheimer's disease who respond poorly to current treatments may be provided. Trial registration: The study protocol is registered with ClinicalTrials.gov (identifier: NCT03115814). Ethics: The study protocol was approved by the Ethics Committee of Chinese PLA General Hospital (approval No. S2015-013-02) and will be performed in accordance with the Declaration of Helsinki formulated by the World Medical Association in 2013. Informed consent: Written informed consent will be obtained from each patient's legal representative.