The purpose of this study is to determine the safety and initial efficacy of Transcranial Electromagnetic Treatment (TEMT) in patients with mild/moderate Alzheimer's Disease. Throughout a 2-month treatment period, patients will be evaluated for cognitive performance, brain energy utilization, functional brain imaging, and blood/cerebrospinal fluid (CSF) markers for Alzheimer's Disease. Since all patients will receive TEMT, each patient's baseline measurements will serve as their own control for any treatment effects.
There is currently no effective therapeutic to stabilize or reverse the cognitive impairment of Alzheimer's Disease (AD) and related dementias. Clinical trials with drugs have been unsuccessful because the wrong therapeutic target/species were selected, because drugs have great difficulty traversing the blood-brain barrier and getting into neurons, and/or because drugs largely have only a single mechanism of action. Since ever-increasing experimental evidence indicates that the toxic forms of both beta-amyloid and tau are the soluble "oligomeric" species of these two proteins, therapeutics to disaggregate these oligomers within neurons represent perhaps the best chance for attaining cognitive benefit in AD patients. Pre-clinical studies performed by the Sponsor and his collaborators have demonstrated that AD transgenic mice treated daily with electromagnetic waves in the radiofrequency (RF) range are protected from cognitive impairment or show a reversal of pre-existing cognitive impairment. These cognitive benefits appear to be due primarily to two complimentary mechanisms: 1) disaggregation of toxic protein oligomers within neurons, and 2) mitochondrial enhancement to increase energy metabolism. Moreover, no deleterious effects of treatment over many months have been observed in these pre-clinical studies. In order to provide similar treatment to mild/moderate Alzheimer's patients clinically, NeuroEM Therapeutics has developed a unique head device that provides electromagnetic (RF) treatment to the entire human forebrain at levels similar to those that provided cognitive benefits in pre-clinical studies. Using the MemorEM 1000 head device in the present Phase I trial, AD patients receive twice daily 1-hour treatments in-home, as administered by their caregiver. The device allows for the patient to have complete mobility for moving throughout their home. A comprehensive array of markers will be analyzed both during and following the 2-month treatment period, with baseline (pre-treatment) values serving as controls. Cognitive safety and efficacy will be evaluated using a variety of cognitive assessments including ADAS-cog (Primary), and secondary cognitive measures including ADCS-ADL, Rey AVLT, Trails A \& B, Digit span, and clock draw tasks. Treatment effects on brain energy metabolism will be determine by FDG-PET scans, while treatment effects on brain functional connectivity will be determined through both resting state MRI and Diffusion Tensor Imaging. Also being assessed are the effects of treatment on various beta-amyloid and tau protein species (e.g., monomers, oligomers) in both blood and CSF. Safety of the treatment will be monitored by regular Adverse Events Assessment, physiologic monitoring, and patient daily diaries maintained by the caregiver. Expected Results: The investigators expect that 2-months of daily electromagnetic (RF) treatment will not present any significant side effects or safety issues. The investigators further expect that cognitive measures will be stable and/or improve by the end of treatment. In addition, the investigators anticipate that brain functional connectivity may be improved and that enhanced brain metabolism (FDG-PET) will occur. Changes in blood/CSF levels of various beta-amyloid and tau species are also anticipated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
The MemorEM 1000 device is self-contained and has been designed for in-home daily electromagnetic treatment in the radiofrequency range, allowing for complete mobility and comfort in performing daily activities during treatment. The device has a custom control panel that is powered by a rechargeable battery. This control panel/battery box is worn on the upper arm and wired to specialized antennas in the head cap worn by the subject. The device provides global RF treatment to the entire forebrain, including deep brain areas. For each of the 60 days of in-home treatment, two one-hour treatment will be given (early morning and late afternoon). Each treatment will be administered by the patient's caregiver, who will position the device on the patient's head and monitor treatment.
Byrd Alzheimer's Institute, University of South Florida
Tampa, Florida, United States
ADAS-Cog
ADAS-Cog is the standard/benchmark test of cognitive performance evaluated in Alzheimer's-related clinical trials.
Time frame: Change from baseline ADAS-Cog at 2 months
FDG-PET
FDG-PET scanning is used to determine brain energy metabolism/utilization
Time frame: Change from baseline FDG-PET at 2 months
Resting state fMRI
rsfMRI is an MRI scan used to evaluate brain functional connectivity
Time frame: Change from baseline rsfMRI at 2 months
Diffusion Tensor Imaging (DTI)
DTI is an MRI scan used to evaluate brain functional connectivity
Time frame: Change from baseline DTI at 2 months
Susceptibility-Weighted Imaging (SWI)
SWI is an MRI scan used to determine any brain microhemorrhages or tumors
Time frame: Change from Baseline SWI at 2 months
Blood and CSF beta-amyloid levels
Blood and CSF will be analyzed for the toxic protein beta-amyloid
Time frame: Change from Baseline beta-amyloid levels at 2 months
Blood and CSF tau levels
Blood and CSF will be analyzed for the toxic protein tau
Time frame: Change from Baseline tau levels at 2 months
Blood and CSF markers of immune function
Blood and CSF will be analyzed for pro- and anti-inflammatory cytokines (same measure units)
Time frame: Change from Baseline pro- and anti-inflammatory cytokine levels at 2 months
Blood and CSF markers of oxidative stress
Blood and CSF will be analyzed for oxidative markers (same measure units)
Time frame: Change from Baseline oxidative stress levels at 2 months
Adverse Event Assessment
AEA will be the primary safety outcome measure
Time frame: Change from Baseline Adverse Event Assessment at 2 months
ADCS-ADL score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline ADCS-ADL score at 2 months
MMSE score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline MMSE score at 2 months
Global Deterioration score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline Global Deterioration score at 2 months
Hachinski score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline Hachinski score at 2 months
Rey AVLT score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline Rey AVLT score at 2 months
Trails A & B score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline Trails A & B scores at 2 months
Digit span score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline Digit span score at 2 months
Clock draw score
This is a secondary cognitive outcome to assess effects of treatment on cognition.
Time frame: Change from Baseline Clock draw score at 2 months
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