Safety and Efficacy of Transcranial Electromagnetic Treatment Against Alzheimer's Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open-Label Study to Evaluate the Safety and Efficacy of Transcranial Electromagnetic Treatment (TEMT) for the Treatment of Alzheimer's Disease

Conditions
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Alzheimer Disease, Alzheimer Disease, Late Onset

Intervention / Treatment
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* Device: MemorEM 1000


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with mild or moderate stage of Alzheimer's Disease, according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. MMSE score 16 to 26 Physical clearance for study participation as evaluated by the clinician. Caregiver (spouse, family member, etc.) who agrees to and is capable of taking care and being responsible for the participation of the patient in the study (keeping a diary of health measures they collect on the patient at home, logging the patient's condition daily, and assuming responsibility for administering daily in-home treatment). Caregiver to have non-impaired mental abilities and normal motor skills, as determined by the investigators at screening. The definition of caregivers for this study is adults providing unpaid care to relatives or friends to help them take care of themselves in such activities as managing finances, shopping, preparing meals, and going to doctor appointments. Agreement to participate in approximately 10 weeks during the study. Normal to near-normal vision and hearing with correction as needed (e.g. corrective lenses, hearing aid). Fluent in English Minimum of 8th grade education Head circumference between 53 - 58 cm (to minimize variability in head antenna locations) If medicated for AD, then use of cholinesterase inhibitors and/or memantine for at least 3 months, on stable dose for at least 60 days prior to screening, and maintenance on that dose for the period of this study. All other non-AD medications must be stable for a period of 4 weeks prior to screening Exclusion Criteria: CDR Global Score of 0, 0.5 or 3 Severe agitation Mental retardation Unstable medical condition Use of benzodiazepines or barbiturates 2 weeks prior to screening Participation in a clinical trial with any investigational agent within 6 months prior to study enrollment and no history of immunotherapy research participation History of Epileptic Seizures or Epilepsy Patients with major depression (not controlled with medication), bipolar disorder or psychotic disorders or any other neurological or psychiatric condition (whether now or in the past). The investigator will obtain this information from available patient medical records, history provided by the patient and caregiver, interview, and neurological exam. Alcoholism or drug addiction as defined by DSM-IV within last 5 years (addicted more than one year and or in remission less than 3 years) or severe sleep deprivation Patients with metal implants in the head, (i.e. cochlear implants, implanted brain stimulators, aneurysm clips) with the exception of metal implants in mouth Patients with vitamin B12 deficiency, abnormal thyroid function, or personal history of either any clinically defined medical disorder or any clinically defined neurological/psychiatric disorder (other than AD), including (but not limited to):, stroke, brain lesions, , cerebrovascular condition, other neurodegenerative disease, significant head trauma (loss of consciousness greater than half an hour, or related anterograde amnesia), multiple sclerosis; or personal history of previous neurosurgery or brain radiation Patients with any signs or symptoms of increased intracranial pressure, as determined in a neurological exam. Patients with demonstrated brain micro-hemorrhages at screening Patients with a score of 4 or higher on the Hachinski Test Patients with a score of 2 or less on the Global Deterioration Scale Patients with hypertension that is unresponsive to anti-hypertensive medications Patients with a history of migraine headaches occurring more than once a month Patients with a history of cancer within the last 3 years Patients chronically taking anticoagulants or anti-platelets (at discretion of Principal Investigator) Pregnant women and women who have the ability to become pregnant Patients with compressed hair thickness of more than 5mm (which could increase distance between head antennas and the scalp). Cardiac pacemakers Implanted medication pumps Intracardiac lines Significant heart disease

Ages Eligible for Study
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Minimum Age: 63 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEMT Treatment<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-Cog | ADAS-Cog is the standard/benchmark test of cognitive performance evaluated in Alzheimer's-related clinical trials. | Change from baseline ADAS-Cog at 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FDG-PET | FDG-PET scanning is used to determine brain energy metabolism/utilization | Change from baseline FDG-PET at 2 months | 
| Resting state fMRI | rsfMRI is an MRI scan used to evaluate brain functional connectivity | Change from baseline rsfMRI at 2 months | 
| Diffusion Tensor Imaging (DTI) | DTI is an MRI scan used to evaluate brain functional connectivity | Change from baseline DTI at 2 months | 
| Susceptibility-Weighted Imaging (SWI) | SWI is an MRI scan used to determine any brain microhemorrhages or tumors | 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 | 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 | 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) | 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) | Change from Baseline oxidative stress levels at 2 months | 
| Adverse Event Assessment | AEA will be the primary safety outcome measure | 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. | Change from Baseline ADCS-ADL score at 2 months | 
| MMSE score | This is a secondary cognitive outcome to assess effects of treatment on cognition. | Change from Baseline MMSE score at 2 months | 
| Global Deterioration score | This is a secondary cognitive outcome to assess effects of treatment on cognition. | Change from Baseline Global Deterioration score at 2 months | 
| Hachinski score | This is a secondary cognitive outcome to assess effects of treatment on cognition. | Change from Baseline Hachinski score at 2 months | 
| Rey AVLT score | This is a secondary cognitive outcome to assess effects of treatment on cognition. | 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. | 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. | 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. | Change from Baseline Clock draw score at 2 months |