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

• ClinicalTrials.gov Identifier: NCT04558164
• Recruitment Status: Recruiting
• First Posted: September 22, 2020
• Last Update Posted: April 15, 2022
• Sponsor: University of California, Los Angeles
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Nanthia Suthana, University of California, Los Angeles

Study Description

Brief 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 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.

Condition or disease	Intervention/treatment	Phase
Cognitive Dysfunction; Memory Disorders in Old Age	Device: Active Theta Burst Stimulation; Device: Sham Theta Burst Stimulation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Network-targeted Theta-burst Stimulation for Episodic Memory Improvement in Mild Cognitive Impairment
• Actual Study Start Date: January 26, 2021
• Estimated Primary Completion Date: June 30, 2024
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Verbal recall performance change [ Time Frame: Baseline: Day 2; During stimulation: Day 3, Day 7, Day 12, Day 17; Follow-up appointments: Day 18, Day 19, Day 20. ]
   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.
2. Object recognition memory performance change [ Time Frame: Baseline: Day 2; During stimulation: Day 3, Day 7, Day 12, Day 17; Follow-up appointments: Day 18, Day 19, Day 20. ]
   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.
3. Associative memory performance change [ Time Frame: Baseline: Day 2; During stimulation: Day 3, Day 7, Day 12, Day 17; Follow-up appointments: Day 18, Day 19, Day 20. ]
   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.

Secondary Outcome Measures :

1. Resting state fMRI functional connectivity [ Time Frame: Baseline (Day 2) before the first treatment and after the last treatment (Day 17) ]
   Resting state fMRI activity will be measured before the first and after the last TBS treatment
2. EEG activity [ Time Frame: During treatment (Days 3, 7 and 12), and after the last treatment (Day 17) ]
   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

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 55-90 years of age
• Right-handedness
• Willing to provide informed consent and participate in a longitudinal study
• In good general health
• Ability to read, write, and speak English fluently
• Adequate visual and auditory acuity to allow neuropsychological testing
• Screening laboratory/ECG without abnormalities that might interfere with the study
• Diagnosis of mild neurocognitive disorder according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) criteria
• Living independently
• Subjective memory complaints (self-report and positive score on MFQ)
• Katz ADL scale: We will exclude potential volunteers scoring < 6
• Lawton iADL scale: We will exclude potential volunteers scoring < 8 (however, having points off is OK if the volunteer never did a task even prior to memory loss (e.g., more men than women never shopped, did laundry, or cooked due to stereotypical social roles). In such an example, the volunteer could score as low as 5 and still be included (no points off for the three activities never done before memory loss).
• MMSE score > 24
• PHQ score > 7
• Hamilton Depression score < 7
• No change in use of psychotropic medication for treatment of depression, anxiety, ADHD or psychosis 1 month prior and during the study.
• At least 1 Standard Deviation below the mean in 2 out of the 3 following tests: BVMT-R (25-minute delay), CVLT-II (20-minute delay), Rey-Osterrieth Complex Figure Task (30-minute delay).

Exclusion Criteria:

• Diagnosis of dementia
• Unwilling or unable to provide informed consent
• Active major psychiatric or neurologic disorders associated with neurocognitive impairment
• Active or history of alcohol or substance abuse
• Recent (< 6 months) alcohol or substance abuse excluding nicotine or caffeine
• Active or history of stroke, 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)
• Head trauma or systemic diseases affecting brain function
• Sleep deprivation
• Uncontrolled hypertension or cardiovascular disease

• 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.
• Current enrollment in a memory-enhancement study or course
• Contraindication to the MRI including claustrophobia, metal in body, surgery within 60 days, certain implants or previous abnormal MRI results.

Contacts and Locations

Contacts

Contact: Sonja Hiller; 3107947517; suthanalab@mednet.ucla.edu

Locations

United States, California

University of California Los Angeles; Recruiting

Los Angeles, California, United States, 90024

Contact: Sonja Hiller 310-794-7517 shiller@mednet.ucla.edu

Sponsors and Collaborators

University of California, Los Angeles

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Nanthia Suthana; University of California, Los Angeles

More Information

• Responsible Party: Nanthia Suthana, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT04558164
• Other Study ID Numbers: 20-001417; R01AG068317 ( U.S. NIH Grant/Contract )
• First Posted: September 22, 2020
• Last Update Posted: April 15, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The data collected for this research represent a valuable resource to the scientific community, and the PIs will make them accessible to others, while respecting the special needs for confidentiality. All data will be anonymized before being provided to the scientific community. Researchers can also request access to the data under collaborative and co-authorship agreements prior to the end of the funding period or before publication. The results from the proposed project will also be shared at scientific meetings (local, national and international) as well via published manuscripts.
• Time Frame: All data will be provided by the time publication occurs or when the proposed funding period has ended.
• Access Criteria: Researchers can request access to the data under collaborative and co-authorship agreements prior to the end of the funding period or before publication.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Memory Disorders; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases