Treatment of Mild Cognitive Impairment With Transcutaneous Vagal Nerve Stimulation (TVNS MCI)

Patients with amnestic mild cognitive impairment (MCI) often have compromised quality of life (QOL). Cognitive impairment is a major contributor to decrements in QOL and progression of MCI often leads to loss of independence and withdrawal from social participation. MCI, in many patients, is an early expression of neurodegenerative disease. Patients with MCI frequently convert to Alzheimer's disease (AD) (12-16 percent by some estimates per year). Treatments for MCI are of limited scope and availability and of limited effectiveness. Thus, there is great need for treatments that can improve cognition and extend QOL in patients with MCI. The investigators propose to investigate the effect of a non-invasive and safe intervention that should have direct influence on brain systems underlying AD, transcutaneous vagal nerve stimulation (tVNS).

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Device: Transcutaneous vagal nerve stimulation; Device: Sham stimulation

Detailed Description

Patients with amnestic mild cognitive impairment (MCI) often have compromised quality of life (QOL). Cognitive impairment is a major contributor to decrements in QOL and progression of MCI often leads to loss of independence and withdrawal from social participation. MCI, in many patients, is an early expression of neurodegenerative disease. Patients with MCI frequently convert to Alzheimer's disease (AD) (12-16 percent by some estimates per year). Treatments for MCI are of limited scope and availability and of limited effectiveness. Thus, there is great need for treatments that can improve cognition and extend QOL in patients with MCI. The investigators propose to investigate the effect of a non-invasive and safe intervention that should have direct influence on brain systems underlying AD, transcutaneous vagal nerve stimulation (tVNS). Transcutaneous vagal nerve stimulation (tVNS) may ameliorate symptoms of MCI. The investigators have demonstrated, in patients with epilepsy, that VNS improves memory; however, tVNS has not been used to treat patients with MCI. tVNS can now be performed without surgery by transcutaneous stimulation of the auricular branch with electrodes on the external ear. tVNS has the potential to improve cognition and may even alter the course of decline in patients with MCI. The investigators will employ a multimodal MRI-based neuroimaging approach combined with comprehensive and targeted cognitive testing to assess changes with tVNS in cognition in patients with MCI.

The investigators will evaluate the effects of tVNS on patients who have been diagnosed with MCI as well as healthy older controls. Very little in the way of mechanistic data or understanding of individual differences in response to tVNS in MCI/AD has been published. Thus, this is a necessary study to evaluate the potential utility of tVNS to enhance cognitive performance in patients with MCI. These data may serve as a platform for supporting the development of a clinical treatment trial with this technology.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Gainesville, Florida, United States, 32608
      • Malcom Randall VA Medical Center
    • Gainesville, Florida, United States, 32608
      • McKnight Brain Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosed with amnestic mild cognitive impairment/mild Alzheimer's disease
• Preservation of independence in functional abilities
• Healthy aged adults without MCI to serve as control group

Exclusion Criteria:

• Other medical or neurological conditions that may be associated with significant impaired cognition (e..g, moderate to severe traumatic brain injury, epilepsy, etc...)
• Vascular dementia or other non-AD spectrum diagnosed neurodegenerative disorders
• Significant current depression
• Uncorrected vision/hearing loss
• Unable to undergo MRI exam

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Initial tVNS; This group will receive transcutaneous vagal nerve stimulation, initially. Participants will be randomized between the two arms of the crossover sessions (initial tVNS vs. initial Sham). Behavioral portions of the testing will then be carried out twice, with at least 72 hours between sessions (to avoid carryover effects).	Device: Transcutaneous vagal nerve stimulation; Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 20Hz, 100 μs pulse width; Device: Sham stimulation; Sham stimulation will be performed using electrodes placed on earlobe
Experimental: Initial Sham; This group will receive sham stimulation, initially. Participants will be randomized between the two arms of the crossover sessions (initial tVNS vs. initial Sham). Behavioral portions of the testing will then be carried out twice, with at least 72 hours between sessions (to avoid carryover effects).	Device: Transcutaneous vagal nerve stimulation; Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device at 20Hz, 100 μs pulse width; Device: Sham stimulation; Sham stimulation will be performed using electrodes placed on earlobe

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rey Auditory Verbal Learning Test (Total Delayed Recall)	The Rey Auditory Verbal Learning Test (RAVLT) is a verbal learning and memory task with a 15-item word list learned over 5 trials. The total delayed recall score is the number of total correct words recalled (ranging from 0 to 15) after a 30 minute delay.	30 minutes after administration of 5 list learning trials; 2 minutes to complete delayed recall of word-list

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute on Aging (NIA); Department of Health and Human Services
• Investigators: Principal Investigator: John B Williamson, Ph.D, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): May 31, 2022
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: November 27, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Mild Cognitive Impairment; Vagal Nerve Stimulation; tVNS
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: IRB201600730 -N-A; R21AG054876 (U.S. NIH Grant/Contract); PRO00011145 (Other Identifier: UFIRST)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes