Back to results

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

Primary Purpose

Alzheimer Disease, Alzheimer Disease, Late Onset

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

MemorEM 1000

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

63 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Byrd Alzheimer's Institute, University of South Florida

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TEMT Treatment

Arm Description

Patients in this arm will receive Transcranial Electromagnetic Treatment (TEMT) twice daily for a two-month treatment period utilizing the MemorEM 1000 head device.

Outcomes

Primary Outcome Measures

ADAS-Cog

ADAS-Cog is the standard/benchmark test of cognitive performance evaluated in Alzheimer's-related clinical trials.

Secondary Outcome Measures

FDG-PET

FDG-PET scanning is used to determine brain energy metabolism/utilization

Resting state fMRI

rsfMRI is an MRI scan used to evaluate brain functional connectivity

Diffusion Tensor Imaging (DTI)

DTI is an MRI scan used to evaluate brain functional connectivity

Susceptibility-Weighted Imaging (SWI)

SWI is an MRI scan used to determine any brain microhemorrhages or tumors

Blood and CSF beta-amyloid levels

Blood and CSF will be analyzed for the toxic protein beta-amyloid

Blood and CSF tau levels

Blood and CSF will be analyzed for the toxic protein tau

Blood and CSF markers of immune function

Blood and CSF will be analyzed for pro- and anti-inflammatory cytokines (same measure units)

Blood and CSF markers of oxidative stress

Blood and CSF will be analyzed for oxidative markers (same measure units)

Adverse Event Assessment

AEA will be the primary safety outcome measure

ADCS-ADL score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

MMSE score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Global Deterioration score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Hachinski score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Rey AVLT score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Trails A & B score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Digit span score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Clock draw score

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Full Information

NCT ID

NCT02958930

First Posted

November 1, 2016

Last Updated

April 22, 2019

Sponsor

NeuroEM Therapeutics, Inc.

Collaborators

Byrd Alzheimer's Institute, University of South Florida, University Diagnostic Institute, Tampa, Invicro, Boston, Left Coast Engineering, Escondido

1. Study Identification

Unique Protocol Identification Number

NCT02958930

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

October 1, 2017 (Actual)

Primary Completion Date

January 4, 2019 (Actual)

Study Completion Date

January 11, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NeuroEM Therapeutics, Inc.

Collaborators

Byrd Alzheimer's Institute, University of South Florida, University Diagnostic Institute, Tampa, Invicro, Boston, Left Coast Engineering, Escondido

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease, Alzheimer Disease, Late Onset

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TEMT Treatment

Arm Type

Experimental

Arm Description

Patients in this arm will receive Transcranial Electromagnetic Treatment (TEMT) twice daily for a two-month treatment period utilizing the MemorEM 1000 head device.

Intervention Type

Device

Intervention Name(s)

MemorEM 1000

Intervention Description

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.

Primary Outcome Measure Information:

Title

ADAS-Cog

Description

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

Secondary Outcome Measure Information:

Title

FDG-PET

Description

FDG-PET scanning is used to determine brain energy metabolism/utilization

Time Frame

Change from baseline FDG-PET at 2 months

Title

Resting state fMRI

Description

rsfMRI is an MRI scan used to evaluate brain functional connectivity

Time Frame

Change from baseline rsfMRI at 2 months

Title

Diffusion Tensor Imaging (DTI)

Description

DTI is an MRI scan used to evaluate brain functional connectivity

Time Frame

Change from baseline DTI at 2 months

Title

Susceptibility-Weighted Imaging (SWI)

Description

SWI is an MRI scan used to determine any brain microhemorrhages or tumors

Time Frame

Change from Baseline SWI at 2 months

Title

Blood and CSF beta-amyloid levels

Description

Blood and CSF will be analyzed for the toxic protein beta-amyloid

Time Frame

Change from Baseline beta-amyloid levels at 2 months

Title

Blood and CSF tau levels

Description

Blood and CSF will be analyzed for the toxic protein tau

Time Frame

Change from Baseline tau levels at 2 months

Title

Blood and CSF markers of immune function

Description

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

Title

Blood and CSF markers of oxidative stress

Description

Blood and CSF will be analyzed for oxidative markers (same measure units)

Time Frame

Change from Baseline oxidative stress levels at 2 months

Title

Adverse Event Assessment

Description

AEA will be the primary safety outcome measure

Time Frame

Change from Baseline Adverse Event Assessment at 2 months

Title

ADCS-ADL score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline ADCS-ADL score at 2 months

Title

MMSE score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline MMSE score at 2 months

Title

Global Deterioration score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline Global Deterioration score at 2 months

Title

Hachinski score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline Hachinski score at 2 months

Title

Rey AVLT score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline Rey AVLT score at 2 months

Title

Trails A & B score

Description

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

Title

Digit span score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline Digit span score at 2 months

Title

Clock draw score

Description

This is a secondary cognitive outcome to assess effects of treatment on cognition.

Time Frame

Change from Baseline Clock draw score at 2 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

63 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amanda Smith, MD

Organizational Affiliation

Byrd Alzheimer's Institute, University of South Florida

Official's Role

Principal Investigator

Facility Information:

Facility Name

Byrd Alzheimer's Institute, University of South Florida

City

Tampa

State/Province

Florida

ZIP/Postal Code

33613

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

It is not anticipated that IPD will be shared with other researchers

Citations:

PubMed Identifier

27258417

Citation

Arendash GW. Review of the Evidence that Transcranial Electromagnetic Treatment will be a Safe and Effective Therapeutic Against Alzheimer's Disease. J Alzheimers Dis. 2016 May 30;53(3):753-71. doi: 10.3233/JAD-160165.

Results Reference

background

PubMed Identifier

22810103

Citation

Arendash GW. Transcranial electromagnetic treatment against Alzheimer's disease: why it has the potential to trump Alzheimer's disease drug development. J Alzheimers Dis. 2012;32(2):243-66. doi: 10.3233/JAD-2012-120943.

Results Reference

background

PubMed Identifier

22558216

Citation

Arendash GW, Mori T, Dorsey M, Gonzalez R, Tajiri N, Borlongan C. Electromagnetic treatment to old Alzheimer's mice reverses beta-amyloid deposition, modifies cerebral blood flow, and provides selected cognitive benefit. PLoS One. 2012;7(4):e35751. doi: 10.1371/journal.pone.0035751. Epub 2012 Apr 25.

Results Reference

background

PubMed Identifier

21514369

Citation

Dragicevic N, Bradshaw PC, Mamcarz M, Lin X, Wang L, Cao C, Arendash GW. Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer's transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit? Neuroscience. 2011 Jun 30;185:135-49. doi: 10.1016/j.neuroscience.2011.04.012. Epub 2011 Apr 13.

Results Reference

background

PubMed Identifier

20061638

Citation

Arendash GW, Sanchez-Ramos J, Mori T, Mamcarz M, Lin X, Runfeldt M, Wang L, Zhang G, Sava V, Tan J, Cao C. Electromagnetic field treatment protects against and reverses cognitive impairment in Alzheimer's disease mice. J Alzheimers Dis. 2010;19(1):191-210. doi: 10.3233/JAD-2010-1228.

Results Reference

background

Citation

Mori T, Arendash GW. Electromagnetic field treatment enhances neuronal activity: Linkage to cognitive benefit and therapeutic implications for Alzheimer's Disease. J Alzheimer's Dis and Parkinsonism 2011: Vol. 1:102, http://dx.doi.org/10.4172/2161-0460.1000102.

Results Reference

background

PubMed Identifier

35585867

Citation

Cao C, Abulaban H, Baranowski R, Wang Y, Bai Y, Lin X, Shen N, Zhang X, Arendash GW. Transcranial Electromagnetic Treatment "Rebalances" Blood and Brain Cytokine Levels in Alzheimer's Patients: A New Mechanism for Reversal of Their Cognitive Impairment. Front Aging Neurosci. 2022 May 2;14:829049. doi: 10.3389/fnagi.2022.829049. eCollection 2022.

Results Reference

derived

Links:

URL

http://www.neuroem.com

Description

Website provides additional information regarding this technology

Learn more about this trial

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

We'll reach out to this number within 24 hrs