While the US has officially said the SARS CoV-2 emergency is over, the country is left
with a residual of patients who continue to experience Post-Acute Sequelae of SARS CoV-2
infection -- PASC. Unfortunately, despite a major effort to understand PASC via the NIH
Researching Covid to Enhance Recovery program, no specific treatment has emerged and only
a limited number of new trials has been initiated. The purpose of this proposal is to
perform a clinical trial of noninvasive, transcutaneous vagus nerve stimulation [tVNS] in
an attempt to find the best tVNS treatment for these patients.
The need for the proposed trial is supported by an earlier open label tVNS trial in 15
PASC patients who also fulfilled the 1994 case criteria for myalgic
encephalomyelitis/chronic fatigue syndrome [ME/CFS but for simplicity CFS]. The research
team chose patients with PASC-CFS for two reasons: first, CFS following Covid infection
is probably the most common subgroup of patients with PASC. In the study, of 41 PASC
patients whose continued symptoms over time lead to their being referred for
cardiopulmonary exercise tests, 47% fulfilled the 1994 case criteria for the diagnosis of
CFS. Second, the research team limited the tVNS pilot to PASC-CFS to reduce the
heterogeneity inherent in the diagnosis of PASC. The research team specifically recruited
non-hospitalized patients with documented Covid who remained ill with fatigue, widespread
pain, cognitive complaints, and post-exertional malaise for at least 6 months after the
acute infection, thus fulfilling the 1994 case criteria for CFS. Importantly, the entire
study was done remotely without requiring participants to come into the medical center or
stop current medical treatments.
The research team proposes to extend this study to inform us which of two possible ways
of stimulating the vagus is the most effective in improving the health of PASC-CFS
patients. The study again will be done remotely with the study team having access to
large databases of non-hospitalized PASC sufferers. After determination that a patient
had Covid, continued ill with PASC and now fulfills criteria for the diagnosis of CFS,
the participant will be asked to respond to questionnaires via RedCap as to magnitude of
fatigue, cognitive dysfunction, widespread pain and/or post-exertional malaise, as well
as their functional status. Each will then be randomized into Treatment A or B and sent
the device for these two treatment limbs with instructions to use the device for 35 min a
day in the morning over a 6-week period.
During the fifth week of study participation, participants will receive a stick-on device
[as well as instructions via zoom] to allow them to use the device to provide data on
heart rate variability - an objective measure of treatment success. Participants will do
this for a 6-minute period in the afternoon and then return the device to the study team.
Participants will complete questionnaires on RedCap at the end of the first 6-week phase
and return the device to the study team to determine usage. Participants will be told
they must use their device for at least 30 of the 42 days in order to get access to the
device that gave the best clinical outcome for an additional 6-weeks. At the end of this
second 6-week period, participants will again complete questionnaires and return their
device to the study team.