Network-targeted Theta-burst Stimulation for Episodic Memory Improvement in Mild Cognitive Impairment

Cognitive Dysfunction Clinical Trial

Official title:

Network-targeted Theta-burst Stimulation for Episodic Memory Improvement in Mild Cognitive Impairment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04558164
• Other study ID #: 20-001417
• Secondary ID: R01AG068317
• Status: Recruiting
• Phase: N/A
• Start date: January 26, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: University of California, Los Angeles
• Contact: Sonja Hiller
• Phone: 310-210-6978
• Email: suthanalab[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see if stimulation of the brain can improve memory. The investigators will use a device called transcranial magnetic stimulation that can stimulate and activate a specific part of the brain that is important for memory. The study will enroll MCI subjects and subjects with subjective memory complaints who will be randomly assigned to receive active or sham brain stimulation. 'Blinded' or 'sham-controlled' means that the subject will not know whether the treatment they receive is the active treatment or the non-active stimulation. In the 'sham' condition, the stimulator will turn on but will not actually be stimulating the target brain region.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: June 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 100 Years

Eligibility

Inclusion Criteria:

• Agreement to participate in the study
• 55-100 years of age
• Right-handedness
• In good general health
• Living independently
• Subjective memory complaints (self-report and positive score on MFQ)
• Katz ADL scale and Lawton iADL scale: We will review scores on a case-by-case basis if they did not score 100%. We will exclude if the scores show impairment in ADLs that suggests problems with independent functioning due to cognitive impairment.
• MMSE score > 24
• PHQ Depression score =< 7
• Ability to read, write, and speak English fluently
• Diagnosis of mild neurocognitive disorder according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) criteria. Participants with subjective memory complaints without an aMCI diagnosis will be reviewed on a case-by-case basis based on neuropsychological scores. Participants scoring a raw score of 0 or 3 standard deviations below normative expectations on the long delay recall in two or more of the three tasks (BVMT-R, RCFT, and CVLT-III) will be excluded.
• No change in use of psychotropic medication for treatment of depression, anxiety, ADHS or psychosis 1 month prior and during the study. Screening diagnostic criteria for aMCI will be subjective memory complaints, intact instrumental and basic activities of daily living (Smith et al., 1996), PHQ, MMSE, BVMT-R (25-minute delay), CVLT-II (20-minute delay), Rey-Osterrieth Complex Figure Task (30-minute delay). Baseline assessments will include neuropsychological testing of all study subjects.

Exclusion Criteria:

• Unwilling or unable to provide informed consent
• Diagnosis of dementia
• Active major medical, psychiatric, or neurologic disorder associated with neurocognitive impairment
• History of alcohol or substance abuse
• Recent (< 6 months) alcohol or substance abuse (excluding nicotine or caffeine)
• History of stroke (if the stroke in our judgment is related to the memory problem), traumatic brain injury with loss of consciousness, or other neurologic disorder (e.g., epilepsy, Huntington's disease, Parkinson's disease)
• Non-English speaking participants
• Not right handed based on self-report or evaluation based on a standard report
• Has received TMS before (not TMS naïve)
• Poorly controlled hypertension or cardiovascular disease
• Current enrollment in a memory-enhancement study or course
• Contraindication to TMS or MRI including claustrophobia, metal in body, surgery within 60 days, certain implants, or previous abnormal MRI results.
• scanning facial tattoos is okay if safe with MRI
• is taking:
• anticholinergic medication (e.g., Detrol, Cogentin);
• sedating antihistamine (e.g., Benadryl);
• any drug that has significant anticholinergic or antihistaminic side effects (e.g., tricyclic antidepressant medications, Remeron).
• benzodiazepines. While not a strict rule out, this will be decided on a case-by-case basis depending on the dose.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Memory Disorders
• Memory Disorders in Old Age

Intervention

Device:
• Active Theta Burst Stimulation
Theta burst transcranial magnetic stimulation (TBS) will be delivered at 80-100% of motor threshold (MT).
• Sham Theta Burst Stimulation
Sham stimulation will be delivered at 0-10% of motor threshold (MT), with all other parameters matching the active TBS condition.

Locations

Country	Name	City	State
United States	University of California Los Angeles	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Verbal recall performance change	Verbal memory will be measured using a free recall task where participants learn a list of everyday words and are asked to recall as many words as they can remember after a period of distraction. Proportion of recollected words will be used to quantify memory performance changes.	Baseline: Day 2; During stimulation: Day 3, Day 7, Day 12, Day 17; Follow-up appointments: Day 18, Day 19, Day 20.
Primary	Object recognition memory performance change	Object memory will be measured using an recognition task where participants view photos of everyday objects and are asked to identify them as OLD or NEW during a memory test wherein unseen novel objects and very similar but new photos of identical objects are shown. Recollection and discrimination index will be used to quantify memory performance changes.	Baseline: Day 2; During stimulation: Day 3, Day 7, Day 12, Day 17; Follow-up appointments: Day 18, Day 19, Day 20.
Primary	Associative memory performance change	Associative memory will be tested using the Face Name Memory Test wherein participants are shown faces and associated names. Participants are then shown faces only and asked to recall the associated name.	Baseline: Day 2; During stimulation: Day 3, Day 7, Day 12, Day 17; Follow-up appointments: Day 18, Day 19, Day 20.
Secondary	Resting state fMRI functional connectivity	Resting state fMRI activity will be measured before the first and after the last TBS treatment	Baseline (Day 2) before the first treatment and after the last treatment (Day 17)
Secondary	EEG activity	EEG functional connectivity with stimulated region and medial temporal source localized power in the theta band will be recorded during a resting period as well as during the treatment itself both before and after treatments	During treatment (Days 3, 7 and 12), after the last treatment (Day 17), and 2 month follow-up session (Day 20)