Diminishing Accelerated Long-term Forgetting in Mild Cognitive Impairment

Summary

This study is designed as a prospective, double-blind, placebo-controlled, randomized parallel-group study that will be completed at the clinical research facility at St. James' Hospital and at Trinity College Dublin, Ireland. A total of 100 amnestic mild cognitive impairment (aMCI) patients will receive a (real or control) non-invasive transcutaneous electrical stimulation procedure. Patients will be assigned to one of four groups. One group will receive active stimulation, while the three groups will be control groups. One groups will be receive sham stimulation (inactive control), while a second group will receive active stimulation and local anesthesia and a third group will stimulate a different nerve (active control; same sensation different nerve). The investigators will include three control groups to verify that the effect is real and location specific and cannot be associated to a sensation effect. The investigators have opted to use a parallel-group design as it is unclear what the carry-over effect and/or wash-out period will be for stimulation. To eliminate subjective bias, all patients and the investigator testing the endpoint measures will be blinded to the type of intervention. The primary outcome, i.e. memory recall, will be determined by a word association task recorded immediately after stimulation, 7 days after stimulation, and 28 days after stimulation. The secondary outcomes is neurophysiological changes determined by resting state EEG, which will be assessed immediately before and after stimulation in the first session.

The investigators will conduct this study as follows:

1. Screening aMCI patients.
2. Randomly assigning aMCI patients to one of the four groups.
3. Administering one session active stimulation (n = 25) or control (n = 25 in each of three control group) stimulation paired with a word-association task; administered by research assistant.
4. Behavioral assessments after each of the three blocks of studying the word associations and neural measures immediately after the last session of Behavioral assessments (T0).
5. Behavioral assessments at seven (T1) and 28 (T2) days after stimulation.

Conditions

• Mild Cognitive Impairment
• Memory Impairment
• Memory Disorders in Old Age

Interventions

DEVICE

NITESGON

NITESGON will be delivered by a specially developed, battery-driven, constant current stimulator via a pair of saline-soaked surface sponges on the scalp. One electrode each will be placed over the left and right C2 dermatomes. NITESGON will first be switched on in a ramp-up fashion over 30 seconds. For active NITESGON, stimulation will occur during the word association task. For sham the current intensity (ramp down) will gradually be reduced (over 5 seconds) as soon as NITESGON reaches a current flow of 1.5 mA. The rationale behind this sham procedure is to mimic the transient skin sensation at the beginning of active NITESGON without producing any conditioning effects on the brain.

DRUG

Lidocaine / Prilocaine Topical Cream

A topical skin anesthetic (lidocaine/prilocaine cream) will be used to reduce any potential contribution from transcutaneous stimulation of peripheral nerves. This lidocaine/prilocaine preparation blocks sodium channels in peripheral nerves in the skin and thereby stabilizes the membrane potential and increases the threshold for firing an action potential.

DEVICE

C5/C6 stimulation

The electrodes will be placed over cervical nerves five and six, to mimic the sensation, but change the location.

DEVICE

Sham NITESGON

Sham NITESGON

Sponsors & Collaborators

• Alzheimer's Association

  collaborator OTHER

• University of Dublin, Trinity College

  lead OTHER

Principal Investigators

• Sven Vanneste, PhD · University of Dublin, Trinity College

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-09-01

Primary Completion

2025-12-31

Completion

2026-01-01

Countries

• Ireland

Study Locations