Pathways Relating Amnestic MCI to a Mild Traumatic Brain Injury History

Phase 2

Recruiting

• Conditions: Amnestic Mild Cognitive Impairment; Mild Traumatic Brain Injury; Mild Cognitive Impairment; Amnestic Mild Cognitive Disorder; Concussion, Brain
• Interventions: Device: High Definition Transcranial Direct Current Stimulation

• Registration Number: NCT05446584
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

This study will probe if the biological changes in amnestic mild cognitive impairment (aMCI) are related to a history of mild traumatic brain injury (mTBI) using high definition transcranial direct current stimulation (HD-tDCS) and blood-derived biomarker tools. Participants who Do as well as those who Do Not have a history of mTBI will be enrolled in the study.

Detailed Description

Ten study visits will be completed by each participant. The initial visit will include a blood draw and a baseline memory evaluation. Afterwards, participants will be randomized to begin with one of 3 conditions of HD-tDCS. The three conditions are sham-control, active stimulation to frontal region, and active stimulation to left temporal region. All participants will be expected to completed each HD-tDCS condition, which will be counterbalanced and separated by 14 days. Active HD-tDCS will be applied at 2 mA for 30 minutes over 3 consecutive daily sessions while sham stimulation will be applied for the same duration and timespan. All subjects will complete memory assessments again immediately following each HD-tDCS condition for a total of four test sessions.

Study Timeline

• Study First Submitted: 2022-06-28
• Study First Submitted QC: 2022-07-05
• Study First Posted: 2022-07-06
• Study Start: 2023-04-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-01
• Last Update Posted: 2025-05-04
• Primary Completion: 2027-05-01
• Study Completion: 2027-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1. Active diagnosis of amnestic mild cognitive impairment
2. Presence of an mTBI history for the mTBI+ group; absence of an mTBI history for a control sample
3. Female and male subjects
4. All races/ethnicities
5. Age 55 years and older
6. Fluent in English

Exclusion Criteria

1. Mild traumatic brain injury within past year
2. Lifetime history of moderate or severe brain injury
3. Lifetime major neurologic syndromes (e.g., stroke, epilepsy, brain tumor)
4. Lifetime major cardiovascular conditions (e.g., heart attack, heart failure)
5. Current substance use disorder
6. Current major psychiatric disorders (e.g., major depressive disorder, bipolar disorder)
7. Current vision or hearing impairment that interferes with testing
8. Any electronic and or metallic implants in the skull or brain
9. Current medication use known to alter HD-tDCS reactivity

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active left temporal HD-tDCS	High Definition Transcranial Direct Current Stimulation	Electrodes will be placed in a 4x1 ring configuration over the left temporal region in accordance with the International 10-10 EEG system. Stimulation will consist of a ramp up period in which the electrical current is gradually increased, 30 minutes of stimulation at 2 mA, and a ramp down period during which the electrical current is gradually removed. Stimulation will be applied back-to-back over three consecutive days.
Active left frontal HD-tDCS	High Definition Transcranial Direct Current Stimulation	Electrodes will be placed in a 4x1 ring configuration over the frontal region in accordance with the International 10-10 EEG system. Stimulation will consist of a ramp up period in which the electrical current is gradually increased, 30 minutes of stimulation at 2 mA, and a ramp down period during which the electrical current is gradually removed. Stimulation will be applied back-to-back over three consecutive days.
Sham HD=tDCS	High Definition Transcranial Direct Current Stimulation	Electrodes will be placed in the same 4x1 ring configuration over the frontal region as the active left frontal condition to ensure a useful control condition. Stimulation will consist of a 30-second ramp up period until reaching 2 mA, followed immediately by a 30-second ramp down, and off for 29 minutes. The same ramp up and down process will be repeated in the final minute of the session to help preserve masking of conditions. Sham stimulation will be applied back-to-back over three consecutive days.

Primary Outcome Measures

Name	Time	Method
Changes in Rey Auditory Verbal Learning Test Score	Baseline and immediately after completion of each HD-tDCS condition	The RAVLT is a verbal episodic memory test that is sensitive to mesial and lateral verbal episodic memory circuit dysfunction. The primary outcome measure for this task is the total number of items immediately recalled during the learning trials and after the 20 minute delayed recall trial. Changes in scores from baseline to testing immediately following the completion of each condition will be examined.

Secondary Outcome Measures

Name	Time	Method
Changes in Delis Kaplan Executive Function System (DKEFS) Trail Making Test	Baseline and immediately after completion of each HD-tDCS condition	The DKEFS Trail Making Test is a measure of cognitive flexibility and executive functions. The task requires the subject to as quickly as possible complete five conditions, involving number cancellation, number sequencing, letter sequencing, number-letter switching, and line tracing. The outcome measure for this task is the time to complete each of the five conditions. Changes in scores from baseline to testing immediately following the completion of each condition will be examined.
Changes in Delis Kaplan Executive Function System (DKEFS) Color-Word Interference Test	Baseline and immediately after completion of each HD-tDCS condition	The DKEFS Color-Word Interference test is a measure of information processing speed and complex attention. The task requires the subject to as quickly as possible complete four conditions, involving color naming, word reading, response inhibition, and then switching back-and-forth between two response patterns. The outcome measure for this task is the time to complete each of the four conditions. Changes in scores from baseline to testing immediately following the completion of each condition will be examined.

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States