The research objective is to assess the safety and potential efficacy of spleenultrasound stimulation as an intervention for Long COVID in a pilot study.Specific Aims include: - Measure Long COVID disease activity before, during and after an 8-week course of spleen-directed daily ultrasound stimulation. - Measure molecular correlates of Long COVID disease activity before, during and after an 8-week course of spleen-directed daily ultrasound stimulation. - Track adverse events throughout the study to assess safety of the ultrasound intervention.
Ultrasound is widely used in human medicine because it is safe, non-invasive, and
painless. The same kind of ultrasound that is used for imaging (for example, to visualize
babies in utero) may be able to treat inflammatory diseases including Long COVID.
In Long COVID, there can be a state of hyperinflammation that persists in those with
symptoms months to years after infection. This hyperinflammatory state includes elevated
proinflammatory cytokines such as interferon β (IFN-β), IFN-λ1, IFN-γ, CXCL9, CXCL10,
interleukin-6 (IL-6), IL-8, IL-1β , and Tumor Necrosis Factor (TNF-α) in those with Long
COVID. Prolonged inflammation in those with Long COVID plays a key role in its
pathogenesis and in driving the persistent symptoms.
This study will employ investigational ultrasound devices produced by SecondWave Systems
called the MINI ultrasound system.
This is a pilot single-arm intervention study in which up to 15 study participants will
receive noninvasive splenic ultrasound therapy over eight weeks (five daily stimulation
sessions per week). Participants will be enrolled in the study for a total of 12 weeks
starting at Week 0. They will undergo a 4-week Baseline Period during which no
intervention is delivered to determine how study outcomes may change over time. Then,
after baseline outcomes are measured at Week 4, the investigational ultrasound
interventional period will begin. Outcomes will be compared from baseline at Week 4
through the end of the 8-week intervention period at Week 12. Investigational
splenic-ultrasound therapy will be delivered with the SecondWave MINI ultrasound system.
The objective of the study is to assess the safety and potential efficacy of spleen
ultrasound stimulation as an intervention for Long COVID in a pilot study.
For ultrasound stimulation, a small wearable ultrasound device is positioned on the upper
left abdomen area over the ribs. Study personnel will use an ultrasound imaging device to
locate the spleen and to position the wearable MINI device in a proper location around
the ribs area. Daily stimulation consists of an approximately 18-minute period for
application of ultrasound to the spleen. Collection of long-COVID outcome data,
patient-reported assessments, and blood draws collected at the 6 study visits to assess
biomarkers of inflammation will be performed in each participant throughout the study.
Stool samples will be collected at 4 timepoints to assess changes in microbiome and
metabolomics over the study period. Movement activity and sleep monitoring will be
collected throughout the day and correlated with other study outcomes.
The study's primary outcome measure is the endurance shuttle walk test (ESWT) and the
secondary outcome measure is the Chalder fatigue scale (CFQ-11). We will also investigate
exploratory outcomes that will include other activity outcomes (e.g., total movement per
day, sleep patterns), vital signs (e.g. heart rate and blood pressure), biomarker
assessments (e.g., CRP, ESR, cortisol), cytokine assessments, microbiome and metabolomic
related assessments, and device usability and experience assessments.
Device: Splenic Ultrasound
Daily ultrasound application to the spleen of approximately 18 minutes per day, 5 days
per week for up to 8 weeks, in addition to standard clinical care.
Other Name: SecondWave Systems investigational MINI device
Inclusion Criteria:
1. Age 18-65 years at the time of enrollment
2. Prior diagnosis of COVID-19 by report, PCR, or home kit
3. Symptoms present for 12 or more weeks that are independent prior to SARS-CoV-2
infection including fatigue and one or more of:
1. Myalgia or general aches/pains
2. Joint pain
3. Dizziness/lightheadedness
4. Cognitive dysfunction (brain fog)
Exclusion Criteria:
1. Candidate who is unable or unwilling to postpone taking new medications used for
treating Long COVID during the study period
2. Candidate that is currently taking immune modifying medications and unable to
maintain stable levels of their immune medication regimen throughout the study
period
3. History of intubation secondary to COVID-19
4. ICU admission for COVID-19
5. Pre-existing Lung conditions such as chronic obstructive pulmonary disease (COPD),
interstitial lung disease (ILD), or severe asthma
6. Pregnant
7. History of coronary artery disease (CAD)
8. History of stroke
9. History of severe anemia of hemoglobin less than 8 g/dl
10. Prior history of Lyme disease
11. Prior history cognitive impairment
12. Any non-marijuana drug abuse history within 30 days
13. Current use of an investigational drug
14. History of prior myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS)
15. History of alcohol abuse: greater than 2 drinks a day for men and 1 drink for
females
16. Prior history of postural orthostatic tachycardia syndrome (POTS)
17. Chronic fatigue secondary to any condition other than COVID-19.
18. Fibromyalgia
19. History of prior chronic pain
20. History of chronic liver disease such as cirrhosis
21. History of splenic pathology such as spleen infarct/splenomegaly
22. History of splenectomy
23. History of Sickle disease with splenic pathology
24. Taking non-approved treatments for Long COVID
25. Participant does not speak English
26. Participant is an active member of the military (service member) or DoD personnel
(including civilian employees)
27. Any other clinical reasons deemed by the investigators of the study in which the
patient would not be an appropriate candidate for the study
University of Minnesota - Phillips-Wangensteen Building
Minneapolis, Minnesota, United States
Farha Ikramuddin, M.D., Principal Investigator
University of Minnesota Medical School, Department of Rehabilitation Medicine