Safety and Efficacy of Transcranial Electromagnetic Treatment Against Alzheimer's Disease
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|ClinicalTrials.gov Identifier: NCT02958930|
Recruitment Status : Enrolling by invitation
First Posted : November 8, 2016
Last Update Posted : March 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease Alzheimer Disease, Late Onset||Device: MemorEM 1000||Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study to Evaluate the Safety and Efficacy of Transcranial Electromagnetic Treatment (TEMT) for the Treatment of Alzheimer's Disease|
|Actual Study Start Date :||October 1, 2017|
|Estimated Primary Completion Date :||August 2018|
|Estimated Study Completion Date :||August 2018|
Experimental: TEMT Treatment
Patients in this arm will receive Transcranial Electromagnetic Treatment (TEMT) twice daily for a two-month treatment period utilizing the MemorEM 1000 head device.
Device: MemorEM 1000
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.
- ADAS-Cog [ Time Frame: Change from baseline ADAS-Cog at 2 months ]ADAS-Cog is the standard/benchmark test of cognitive performance evaluated in Alzheimer's-related clinical trials.
- FDG-PET [ Time Frame: Change from baseline FDG-PET at 2 months ]FDG-PET scanning is used to determine brain energy metabolism/utilization
- Resting state fMRI [ Time Frame: Change from baseline rsfMRI at 2 months ]rsfMRI is an MRI scan used to evaluate brain functional connectivity
- Diffusion Tensor Imaging (DTI) [ Time Frame: Change from baseline DTI at 2 months ]DTI is an MRI scan used to evaluate brain functional connectivity
- Susceptibility-Weighted Imaging (SWI) [ Time Frame: Change from Baseline SWI at 2 months ]SWI is an MRI scan used to determine any brain microhemorrhages or tumors
- Blood and CSF beta-amyloid levels [ Time Frame: Change from Baseline beta-amyloid levels at 2 months ]Blood and CSF will be analyzed for the toxic protein beta-amyloid
- Blood and CSF tau levels [ Time Frame: Change from Baseline tau levels at 2 months ]Blood and CSF will be analyzed for the toxic protein tau
- Blood and CSF markers of immune function [ Time Frame: Change from Baseline pro- and anti-inflammatory cytokine levels at 2 months ]Blood and CSF will be analyzed for pro- and anti-inflammatory cytokines (same measure units)
- Blood and CSF markers of oxidative stress [ Time Frame: Change from Baseline oxidative stress levels at 2 months ]Blood and CSF will be analyzed for oxidative markers (same measure units)
- Adverse Event Assessment [ Time Frame: Change from Baseline Adverse Event Assessment at 2 months ]AEA will be the primary safety outcome measure
- ADCS-ADL score [ Time Frame: Change from Baseline ADCS-ADL score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- MMSE score [ Time Frame: Change from Baseline MMSE score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- Global Deterioration score [ Time Frame: Change from Baseline Global Deterioration score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- Hachinski score [ Time Frame: Change from Baseline Hachinski score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- Rey AVLT score [ Time Frame: Change from Baseline Rey AVLT score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- Trails A & B score [ Time Frame: Change from Baseline Trails A & B scores at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- Digit span score [ Time Frame: Change from Baseline Digit span score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
- Clock draw score [ Time Frame: Change from Baseline Clock draw score at 2 months ]This is a secondary cognitive outcome to assess effects of treatment on cognition.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02958930
|United States, Florida|
|Byrd Alzheimer's Institute, University of South Florida|
|Tampa, Florida, United States, 33613|
|Principal Investigator:||Amanda Smith, MD||Byrd Alzheimer's Institute, University of South Florida|