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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| active rTMS | Active Comparator | 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). |
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| Sham rTMS | Sham Comparator | The rTMS magnet will be set to sham stimulation without the knowledge of the treating doctors or the research team. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rTMS | Device | 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). |
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Helen Lavretsky, MD | University of California, Los Angeles | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Semel Institute | Los Angeles | California | 90095 | United States |
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| ID | Term |
|---|---|
| D000094024 | Post-Acute COVID-19 Syndrome |
| D005222 | Mental Fatigue |
| D005221 | Fatigue |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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All participants and investigators and outcomes assessors will be blind to the assignment to active or sham rTMS
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| 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. |
| D007239 |
| Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000094025 | Post-Infectious Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |