Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)

University of New Mexico (UNM)

Status and phase: Enrolling; Phase 2

Conditions: PASC; Long COVID Syndrome; Long COVID; Long COVID-19 Syndrome; PASC Post Acute Sequelae of COVID 19

Treatments: Device: accelerated intermittent theta burst stimulation

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06940609

HT9425-24-1-0742 (Other Grant/Funding Number)

24-470

Details and patient eligibility

About

The goal of this clinical trial is to test whether a type of rapid outpatient brain stimulation that uses magnetic fields, called accelerated intermittent theta burst stimulation (iTBS), can treat symptoms such as brain fog, depression, and anxiety in patients with Long COVID. The main questions it aims to answer are:

• Is iTBS effective and feasible for reducing Long COVID symptoms? We will measure these symptoms using the Symptom Burden Questionnaire.
• Are there changes in inflammatory brain chemicals associated with treatment with iTBS? We will be looking at levels of choline in the brain, which is thought to be related to inflammation.

Researchers will compare sham versus active forms of iTBS to see if the active group has greater improvement in symptoms.

Participants will complete symptom surveys, cognitive tests, and magnetic resonance imaging scans at the beginning, middle, and end of treatment.

Full description

Chronic neuropsychiatric symptoms of post-acute sequelae of COVID-19 (neuro-PASC) can lead to disability, loss of function, and reduced quality of life, but there are currently no validated effective treatments. We propose a randomized sham-controlled trial of "Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)." We will deliver active or sham accelerated iTBS (5x/day, 10 days, 25 blinded sessions followed by 25 open-label sessions) to each participant's brain target. We will assess neuro-PASC symptoms, mood, anxiety, cognition, and quality of life from baseline to end-of-treatment. We will correlate symptom improvement with clinical and imaging variables.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. aged 18-80
2. a documented diagnosis of PASC with evidence of ongoing symptoms as demonstrated by score of 12 on the NIH RECOVER Symptom List
3. have "brain fog" or cognitive difficulties as one of the ongoing symptoms
4. are fluent in English
5. if taking psychotropic medications, have been on stable doses for the past month.

Exclusion criteria

1. a prior history of other neurological disease, or any history of seizures, so as to reduce risk of exacerbation of epilepsy or other neurological symptoms;
2. history of a psychotic disorder, such as schizophrenia or bipolar disorder, so as to reduce risk of psychiatric decompensation
3. history of ongoing substance/alcohol dependence, to reduce confounding effects on diagnosis and brain imaging
4. presence of any implanted electrical device (e.g., pacemaker), to reduce risk of device malfunction from rTMS
5. recent medical hospitalization (within four weeks), to reduce risk of medical decompensation during the study
6. any condition that would prevent the subject from completing the protocol
7. appointment of a legal representative, to avoid coercion of a vulnerable population
8. any ongoing litigation related to medical diagnosis, or disability, to prevent interference with legal proceedings
9. any contraindication to MRI
10. membership in an identified vulnerable population, including minors, pregnant women, and prisoners, so as to prevent coercion.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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60 participants in 2 patient groups

Sham accelerated iTBS

Sham Comparator group

Description:

Sham stimulation is delivered using the same coil as active stimulation, producing an equivalent sound, however it is shielded so that no effective magnetic field reaches the participant's brain. To blind participants to active versus sham condition, a mild electrical skin stimulation that has no brain effects is delivered simultaneously with iTBS at the scalp to both active and sham groups, creating the same sense of skin sensation in both groups.

Treatment:

Device: accelerated intermittent theta burst stimulation

Active accelerated iTBS

Experimental group

Description:

Participants will be assigned to receive fMRI-guided iTBS (5 days, 5 sessions/day) to the left dorsolateral prefrontal cortex (dlPFC) during the sham-controlled phase. Each participant is invited to undergo 25 more sessions (5 more days) of open label, unblinded active accelerated fMRI-guided iTBS to the left dlPFC.

Treatment:

Device: accelerated intermittent theta burst stimulation