Fornix and NbM as Targets of Stimulation In Alzheimer's Disease (FANTASIA)

A Randomized Controlled Study of 12 Months to Evaluate the Safety and Efficacy of Deep Brain Stimulation(DBS) to the Fornix & Meynert Nucleus(NbM) in Patients With Mild to Moderate Alzheimer's Disease(AD)

The primary goal of this study is to evaluate the efficacy and safety of the DBS to the fornix/NbM among patients who are diagnosed as AD according to a series of evaluations including cerebrospinal fluid (CSF) biomarkers and molecular imaging examinations; The secondary goal is to compare the efficacy among the two treatment groups of different targets.

Study Overview

• Status: Unknown
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: DBS of the fornix, power on; Device: DBS of the NbM, power on; Device: DBS of the fornix, power off; Device: DBS of the NbM, power off

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guo-Guang Zhao, M.D.; Phone Number: +86-010-63037023; Email: ggzhao@vip.sina.com

Study Locations

• China
  • Beijing, China, 100053
    • Recruiting
    • Xuanwu Hospital, Capital Medical University.
    • Contact: Peng-Hu Wei, M.D.; Phone Number: +86-18601986863

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with informed consent;
2. 45-75 years of age;
3. At least 6 years of education;
4. AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) guidelines (McKhann et al., 2011);
5. Clinical Dementia Rating Scale (CDR): 1.0-2.0;
6. Positive findings with amyloid PET imaging;
7. Stable prescription of donepezil (5mg, qd) for at least 3 months, and without any intentions to modify the dosage during the observation period.

Exclusion Criteria:

1. Fazekas scale>2;
2. Neuropsychiatric inventory (NPI) total score ≥10, or any subdomain≥4；
3. Modified Hachinski ischemic score>4；
4. Young Mania Rating Scale>11(Young, Biggs, Ziegler, & Meyer, 1978);
5. Any suicidal tendencies in recent 2 years;
6. Cornell Scale for Depression and Dementia>10;
7. Familial AD;
8. Abnormal brain structural magnetic resonance imaging (MRI) scan, including hydrocephalus, stroke, structural lesions, etc. that would potentially confound the outcome;
9. Surgical history of the central nervous system;
10. Severe cardiovascular/pulmonary disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DBS of the fornix, power on	Device: DBS of the fornix, power on; DBS of bilateral columns of the fornix is performed, with the power of the device on since the 1st month after the implantation. Observations will start at the time when the device is turning on . DBS system includes: Pins G102 Implantable Neurostimulator; Pins L301 DBS Electrode； Pins E202 DBS extension lead
Experimental: DBS of the NbM, power on	Device: DBS of the NbM, power on; DBS of bilateral NbMs is performed, with the power of the device on since the 1st month after the implantation. Observations will start at the time when the device is turning on . DBS system includes: Pins G102 Implantable Neurostimulator; Pins L301 DBS Electrode； Pins E202 DBS extension lead
Sham Comparator: DBS of the fornix, power off	Device: DBS of the fornix, power off; DBS of bilateral columns of the fornix is performed, the power of the device is going to keep off during the first 7 months after the implantation. Observations will start after 1 month of the implantation. DBS system includes: Pins G102 Implantable Neurostimulator; Pins L301 DBS Electrode； Pins E202 DBS extension lead
Sham Comparator: DBS of the NbM, power off	Device: DBS of the NbM, power off; DBS of bilateral NbMs is performed, the power of the device is going to keep off during the first 7 months after the implantation. Observations will start after 1 month of the implantation. DBS system includes: Pins G102 Implantable Neurostimulator; Pins L301 DBS Electrode； Pins E202 DBS extension lead
No Intervention: Control group; The patients are going to prescribe stable dosage of donepezil during observation period without surgical interference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive outcome	Cognitive function measured by Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog, 13-items version). ADAS-cog 13 scale range: 0-80; (Higher value represents a worse outcome)	12 months (from 1 month to 13 month after implantation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroplasticity outcome	Protection of hippocampal volume revealed by magnetic resonance imaging (MRI).	12 months (from 1 month to 13 month after implantation)
Neuroplasticity outcome	Improved cerebral metabolic level revealed by FDG positron emission tomography(PET) imaging.	12 months (from 1 month to 13 month after implantation)
Cognitive outcome	Improvement of cognitive function evaluated by Clinical Dementia Rating Scale sum of the boxes (CDR-SB). CDR-SB scale range: 0-18; ("0" represents normal cognition, the higher the score, the worse the cognitive function).	12 months (from 1 month to 13 month after implantation)
Functional outcome	Improvement of life quality according to Activities of Daily Living (ADL) scale. ADL scale range: 20-80 ("20" represents normal life ability, the higher the score, the worse the life ability).	12 months (from 1 month to 13 month after implantation)
Safety outcome	Device/therapy related side effects or complications such as mortality an morbidity.	12 months (from 1 month to 13 month after implantation)

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Beijing Pins Medical Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: November 16, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Actual): January 11, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: XuanwuH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No