A Pilot rTMS Trial for Neuropsychiatric Symptoms of Long-COVID

A Pilot Randomized Trial of rTMS for Fatigue and Brain Fog and Neuropsychiatric Symptoms of Long-COVID.

This is a pilot randomized trial of rTMS for symptoms of fatigue and brain fog, and other neuropsychiatric symptoms of Long-COVID (Post-COVID, post-acute sequelae of COVID-19 infection, PASC). Twenty participants diagnosed with Long-COVID and recruited from the UCLA Long-COVID clinic will be randomized to receive active rTMS versus sham stimulation for 15 treatments followed by another 15 open-label rTMS treatments. Investigators will compare the safety and tolerability of rTMS vs Sham and examine within-group changes in symptoms of fatigue, sleep, pain, mood, and subjective and objective cognitive impairment. This project will provide information and pilot data for future larger clinical trials.

Study Overview

• Status: Active, not recruiting
• Conditions: Fatigue; Long Covid-19; Brain Fog; PASC Post Acute Sequelae of COVID 19
• Intervention / Treatment: Device: rTMS

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Semel Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18+ years of age
2. Prior hx of PCR confirmed COVID-19 infection. Determined by the PI or participant's physician.
3. Subsequent development of post-acute neuropsychiatric symptoms with fatigue and brain fog as primary outcomes
4. USE of Psychotropic medications
5. Stable on psychotropic medications for 4+ months
6. Confirmed diagnosis of Long COVID
7. Subjects are willing and able to adhere to the treatment schedule and required study visits

Exclusion Criteria:

1. Mentally or legally incapacitated or unable to give informed consent
2. MOCA < or = 24
3. Infection of poor skin condition over the scalp where the rTMS device will be positioned
4. Pregnancy: Female participants will be tested for pregnancy at baseline and agree to use a medically acceptable form of birth control throughout the study, for women younger than 60.
5. Lifetime history of diagnosed bipolar disorder; psychosis, such as schizophrenia, schizophreniform, or schizoaffective disorder; intellectual disability (intellectual developmental disorder); organic brain damage; or suicide attempts in the past 24 months.
6. Severe MDD with suicidality of Psychosis- excluded
7. As-needed use of benzodiazepines and beta-blockers will be permitted but discouraged during assessment days.
8. Current abuse or dependence on alcohol or any illicit drug of abuse (disorder in last 6 months). Any recent use of cocaine or opiates will also be exclusionary.
9. Participants with asthma or with a history of serious, uncontrolled medical illness or instability (including significant cardio-pulmonary disease, organic brain including significant cardio-pulmonary syndrome, pre-existing dementia, seizure disorder, cerebrovascular disease, and diabetes)
10. Taking medications known to lower seizure thresholds (Clozaril/ Wellbutrin)
11. Neurological conditions that include epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, having a history of repetitive or severe head trauma, or primary or secondary tumors in the central nervous system.
12. Presence of an implanted metallic and magnetic-sensitive medical device present in the body scan, including but not limited to a cochlear implant, infusion pump, implanted cardioverter defibrillator, pacemaker, vagus nerve stimulator, aneurysm clip, metal prosthesis, or metal aneurysm clips or coils, staples, or stents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active rTMS; The rTMS magnet will be set to active stimulation without the knowledge of treating doctors or research team. Only one technician will know the randomization list assignment and will adjust the settings. rTMS treatment will include rTMS to the left dorsolateral prefrontal cortex (DLPFC), followed by rTMS to left primary motor cortex (M1).	Device: rTMS; Participants will be randomized to 15 sessions of double-blind multi-target rTMS treatment (active vs sham) and then will receive only open-label active stimulation for another 15 sessions. Each session will include rTMS to the left dorsolateral prefrontal cortex (DLPFC), followed by rTMS to left primary motor cortex (M1).; Other Names: repetitive transcranial magnetic stimulation
Sham Comparator: Sham rTMS; The rTMS magnet will be set to sham stimulation without the knowledge of the treating doctors or the research team.	Device: rTMS; Participants will be randomized to 15 sessions of double-blind multi-target rTMS treatment (active vs sham) and then will receive only open-label active stimulation for another 15 sessions. Each session will include rTMS to the left dorsolateral prefrontal cortex (DLPFC), followed by rTMS to left primary motor cortex (M1).; Other Names: repetitive transcranial magnetic stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability as measured by Safteesi survey	Safteesi is an instrument that assesses any new symptom(s) that participants developed since starting the clinical study.	Baseline, after every 5th treatment, through study completion, an average of 12 weeks.
Safety profile and adverse events	Study patients will be monitored weekly for the occurrence of adverse events.	Baseline, after every 5th treatment, through study completion, an average of 12 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Cognitive impairment assessed by Multidimensional Inventory of Subjective Cognitive Impairment (MISCI)	MISC is a brief 10-item survey that measures perceived cognitive function. The MISCI is normally distributed and has low rates of ceiling and floor effects, excellent internal consistency, and good construct validity in correlation with other measures.	Baseline, after every 5th treatment, through study completion, an average of 12 weeks.
Fatigue assessed by Fatigue Severity Scale (FSS)	The FSS is a nine-item, self-report instrument designed to assess fatigue as a symptom of different chronic conditions and disorders. The scale addresses fatigue's effect on daily functioning and its relationship to motivation, physical activity, work, family, and social life. Participants will rate the ease with which they are fatigued and the degree to which the symptoms pose a problem. Scoring uses a scale that ranges from 1 (completely disagree) to 7 (completely agree) to indicate agreement with the nine statements about fatigue.	Baseline, after every 5th treatment, through study completion, an average of 12 weeks.
Physical and mental health assessed by PROMIS-29	The PROMIS-29 measures pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) using four items for each domain.	Baseline, through study completion, an average of 12 weeks.
Alzheimer's Disease Assessment Scale (ADAS-Cog)	Cognitive performance will be assessed by ADAS-Cog	Baseline through study completion, an average of 12 weeks.
Fatigue assessed by VAS for Fatigue Questionnaire	VAS is a one-question self-report survey that asks "How much fatigue are you having now?" on a scale of 0 (no fatigue) to 10 (worst possible fatigue).	Baseline, after every 5th treatment, through study completion, an average of 12 weeks.
DKEFS CW	Verbally mediated processing speed and executive functioning will be assessed using the DKEFS Color Word Test.	Baseline through study completion, an average of 12 weeks.
Verbal Fluency test	The Verbal Fluency test will be used to assess global cognitive abilities.	Baseline through study completion, an average of 12 weeks.
DKEFS Trailmaking A,B	Speed for attention, sequencing, mental flexibility, visual search, and motor functioning will be assessed by the DKEFS Trailmaking tests.	Baseline through study completion, an average of 12 weeks.
Test of Premorbid Functioning (TOPF)	TOPF will be used to estimate pre-morbid cognitive and memory functioning.	Baseline
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	RBANS story memory subtest is used to assess immediate memory.	Baseline through study completion, an average of 12 weeks.
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	RBANS story recall subtest will be used to assess delayed memory	Baseline through study completion, an average of 12 weeks.
Repeatable Battery for the Assessment of Neuropsychological (RBANS)	Processing speed, short-term visual memory, psychomotor speed, cognitive flexibility, concentration, and motivation will be assessed by RBANS Coding subtest.	Baseline through study completion, an average of 12 weeks.
DKEFS CWI	Selective attention, cognitive flexibility, and processing speed will be assessed by the DKEFS Color Word Interference test.	Baseline through study completion, an average of 12 weeks.

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Helen Lavretsky, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): June 15, 2026

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: September 3, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Behavioral Symptoms; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Post-Acute COVID-19 Syndrome; Fatigue; Mental Fatigue; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: 24-000555

Drug and device information, study documents

• 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