Clinical trial NCT01608061: ADvance DBS-f in Patients With Mild Probable Alzheimer's Disease
Official title: A Twelve Month Double-blind Randomized Controlled Feasibility Study to Evaluate the Safety, Efficacy and Tolerability of Deep Brain Stimulation of the Fornix (DBS-f) in Patients With Mild Probable Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease
Keywords: Mild probable Alzheimer's Disease
Lead sponsor: Functional Neuromodulation Ltd
Sponsor class: INDUSTRY
First posted: 2012-05-30
Enrollment: 42
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this feasibility study is to evaluate the safety of DBS-f in patients with mild Alzheimer's disease by assessing all device and/or therapy related adverse events. The secondary objective is to preliminarily estimate the treatment effect size on the outcomes of interest at 12 months post-randomization. The objectives do not involve formal tests of hypotheses.


Eligibility criteria: Inclusion Criteria:

1. 45-85 years of age (inclusive)
2. Probable Alzheimer's disease according to the National Institute of Aging Alzheimer's disease Association criteria.
3. Must meet certain criteria on cognitive and behavioral rating scales
4. If female, subjects who are post-menopausal or surgically sterile or willing to use birth control methods for the duration of the study.
5. An available caregiver willing to participate.
6. Subject is living at home and likely to remain at home for the study duration.
7. The subject is currently taking a stable dose of cholinesterase inhibitor (AChEI) medication for at least 60 days

Exclusion Criteria:

1. Must meet certain criteria on cognitive and behavioral rating scales
2. Current major psychiatric disorder such as schizophrenia, bipolar disorder or major depressive disorder based on psychiatric consult at screening visit
3. History of head trauma in the 2 years prior to signing the consent to participate in the study
4. History of brain tumor, subdural hematoma, or other clinically significant (in the judgment of the investigator) space-occupying lesion on CT or MRI
5. Active psychiatric disorder
6. Mental retardation
7. Current alcohol or substance abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)
8. Contraindications for PET scanning (e.g., insulin dependent diabetes)
9. Contraindications for MRI scanning, including implanted metallic devices (e.g. non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
10. Abnormal lab results that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
11. Abnormal cardiovascular or neurovascular disorder that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
12. Unstable doses of any medication prescribed for the treatment of memory loss or Alzheimer's disease.
13. Currently prescribed any non-AD medications that, in the opinion of the investigator and/or enrollment review committee, would preclude participation in the study.
14. Is unable or unwilling to comply with protocol follow-up requirements.
15. Has a life expectancy of \< 1 year.
16. Is actively enrolled in another concurrent clinical trial.

Primary outcomes:
measure: Acute Safety
timeFrame: 30 days post implant
measure: Long Term Safety. Not Based on Formal Hypotheses.
timeFrame: 12 month
Secondary outcomes:
measure: ADAS-Cog 13
timeFrame: Baseline and 12 months
measure: CDR-SB
timeFrame: Baseline and 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Research Institute at Sun City
state: Arizona
city: Gainesville
country: United States
facility: University of Florida at Gainesville
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Bayview
state: Maryland
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania: Penn Memory Clinic
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Andres Lozano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Constantine G Lyketsos, MD, MHS, DFAPA, FAPM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lozano AM, Fosdick L, Chakravarty MM, Leoutsakos JM, Munro C, Oh E, Drake KE, Lyman CH, Rosenberg PB, Anderson WS, Tang-Wai DF, Pendergrass JC, Salloway S, Asaad WF, Ponce FA, Burke A, Sabbagh M, Wolk DA, Baltuch G, Okun MS, Foote KD, McAndrews MP, Giacobbe P, Targum SD, Lyketsos CG, Smith GS. A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease. J Alzheimers Dis. 2016 Sep 6;54(2):777-87. doi: 10.3233/JAD-160017.
citation: Ponce FA, Asaad WF, Foote KD, Anderson WS, Rees Cosgrove G, Baltuch GH, Beasley K, Reymers DE, Oh ES, Targum SD, Smith GS, Lyketsos CG, Lozano AM; ADvance Research Group. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial. J Neurosurg. 2016 Jul;125(1):75-84. doi: 10.3171/2015.6.JNS15716. Epub 2015 Dec 18.