Post Covid-19 Patients
Conditions
Keywords
Covid-19, Fatigue
Brief summary
The objective of this study is to investigate the short- and long-term effects of multiple sessions of 4 mA M1 tDCS on fatigue and brain activity in recovered COVID-19 patients using established measures of perception of fatigue, performance fatigability, and cerebral glucose uptake. Our central hypothesis is that tDCS will improve fatigue short- and long-term, and thus will improve quality of life (QOL) in recovered COVID-19 patients and that these changes will be associated with alterations in brain activity.
Detailed description
For survivors of severe COVID-19, overcoming the virus is just the beginning of an uncharted recovery path. As the number of confirmed COVID-19 cases exceeds 27 million globally and 6 million in the US, the number of patients who experience persistent symptoms during recovery is rapidly growing. In COVID-19 patients, common acute symptoms include cough, fever, dyspnea, musculoskeletal symptoms (myalgia, joint pain, fatigue), gastrointestinal symptoms, and anosmia/dysgeusia . Clinicians and researchers have focused on the acute phase of COVID-19, but continued monitoring and treating of persistent symptoms is urgently needed. Recent studies assessed persistent symptoms in patients who were discharged from the hospital after recovering from COVID-19. None of the patients had a fever or any of the other signs or symptoms associated with acute illness. Nevertheless, decreased quality of life was observed in 44.1% and fatigue was reported by 53.1% and 71% of patients. Furthermore, persistent fatigue following COVID-19 infection is common and independent of severity of initial infection (hospitalized and non-hospitalized patients). In addition to the characteristic laboratory findings and lung computed tomography (CT) abnormalities, it has been recently reported that patients with COVID-19 also have neurological manifestations. Wu et al. \[2020\] found that viral infections have detrimental impacts on neurological functions and can even cause severe neurological damage. Their study showed that coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibited neurotropic properties and may cause neurological diseases with severe fatigue symptoms. Another recent case report has also indicated reduced glucose uptake (\[18F\]flurodeoxyglucose (FDG); measured with positron emission tomography (PET)) in diverse brain areas \[9\], which may contribute to these neurological manifestations. Therefore, there is a critical need to develop inexpensive, effective, and rapid treatments for the persistent fatigue experienced by recovered COVID-19 patients. Without such treatments, these patients will continue to experience fatiguing symptoms that significantly reduce their quality of life. One possible treatment modality is transcranial direct current stimulation (tDCS) \[10\]. tDCS uses weak currents applied to the scalp to alter the excitability of cortical neurons by changing their spontaneous firing rate. It also has a favorable safety profile and only transient adverse side effects. Studies in patients with neurological disorders have shown that tDCS over the primary motor and/or sensory cortex (M1/S1) consistently and significantly improves fatigue. M1 tDCS represents an easy, cost-effective candidate for treating persistent fatigue in recovered COVID-19 patients.
Interventions
Transcranial Direct Current Stimulation is a form of non-invasive brain stimulation. It uses small electrodes to deliver small amounts of current to specific areas of the brain to either increase or decrease excitability.
Transcranial Direct Current Stimulation is a form of non-invasive brain stimulation. It uses small electrodes to deliver small amounts of current to specific areas of the brain to either increase or decrease excitability.
Sponsors
Study design
Eligibility
Inclusion criteria
Only those that are discharged from the UIHC COVID-19 inpatient clinic and/or that meet the CDC guidelines for discontinuing home isolation (i.e., fever free for at least 24 hours, all symptoms improved after 10 days) will initially be considered as long as they meet the rest of the following criteria: Inclusion criteria 1. 18-80 yrs. 2. Meet CDC guidelines (https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html) for discontinuation of home isolation 3. Meet the criteria for fatigue, based on the Chalder Fatigue Scale CFQ-11 case definition of fatigue 4. Healthy enough to complete the protocol based, on information obtained from a clinical exam and past medical history, such as cardiovascular disease. 5. Comprehension of the protocol, as indicated by an ability to respond to questions about the study after reading the consent form. 6. Able to use and be contacted by telephone 7. Able to speak, read, and understand English, and complete questionnaires in English
Exclusion criteria
1. Medical diagnosis or condition that is considered to be an absolute or relative contraindication to participating in exercise training, such as major renal, pulmonary, hepatic, cardiac, gastrointestinal, HIV, cancer (other than treated basal cell cancer), or neurological disorders 2. History/presence of secondary conditions such as seizure disorders (or on medications known to lower seizure threshold), hydrocephalus, diabetes mellitus, or claustrophobia 3. Alcohol dependence or abuse (\>2 drinks/day), or present history of drug abuse (last six months) 4. History of significant traumatic brain injury or hydrocephalus 5. Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-minute Walk Test | through study completion, an average of 8 weeks | Distance in meters will be measured in six minutes |
| Fatigue Assessment Scale (FAS) | through study completion, an average of 8 weeks | Fatigue Questionnaire (1 to 5-point scale x 10 questions for a total score range of 0 to 50) where a low value indicates less fatigued (better outcome) and a high value indicates more fatigued (worse outcome) |
| Fatigue Severity Scale (FSS) | through study completion, an average of 8 weeks | Fatigue Questionnaire (1 to 7 point scale x 9 questions for a total score range of 0 to 63) with a low value indicating less severe fatigue (better outcome) and a high value indicating more severe fatigue (worse outcome) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| tDCS and Fatigue This group will receive the active form of tDCS.
Transcranial Direct Current Stimulation: Transcranial Direct Current Stimulation is a form of non-invasive brain stimulation. It uses small electrodes to deliver small amounts of current to specific areas of the brain to either increase or decrease excitability. | 22 |
| Sham and Fatigue This group will receive the sham form of tDCS.
Sham Transcranial Direct Current Stimulation | 19 |
| tDCS and Non-fatigue This group will receive the active form of tDCS.
Transcranial Direct Current Stimulation: Transcranial Direct Current Stimulation is a form of non-invasive brain stimulation. It uses small electrodes to deliver small amounts of current to specific areas of the brain to either increase or decrease excitability. | 10 |
| Sham and Non-fatigue This group will receive the sham form of tDCS.
Sham Transcranial Direct Current Stimulation | 10 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 8 | 0 | 0 |
Baseline characteristics
| Characteristic | tDCS and Fatigue | Sham and Fatigue | tDCS and Non-fatigue | Sham and Non-fatigue | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 19 Participants | 10 Participants | 10 Participants | 61 Participants |
| Age, Continuous | 37.23 Years STANDARD_DEVIATION 11.71 | 36.74 Years STANDARD_DEVIATION 14.37 | 30.13 Years STANDARD_DEVIATION 10.02 | 30.13 Years STANDARD_DEVIATION 10.02 | 34.30 Years STANDARD_DEVIATION 14.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 17 Participants | 10 Participants | 8 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 17 Participants | 17 Participants | 9 Participants | 6 Participants | 49 Participants |
| Region of Enrollment United States | 22 Participants | 19 Participants | 10 Participants | 10 Participants | 61 Participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 6 Participants | 7 Participants | 43 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 4 Participants | 3 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 27 | 0 / 27 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 10 | 0 / 10 |
Outcome results
6-minute Walk Test
Distance in meters will be measured in six minutes
Time frame: through study completion, an average of 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tDCS and Fatigue | 6-minute Walk Test | 435.4 meters | Standard Deviation 70.47 |
| Sham and Fatigue | 6-minute Walk Test | 460.69 meters | Standard Deviation 58.67 |
| tDCS and Non-fatigue | 6-minute Walk Test | 489.01 meters | Standard Deviation 68.11 |
| Sham and Non-fatigue | 6-minute Walk Test | 451.38 meters | Standard Deviation 65.86 |
Fatigue Assessment Scale (FAS)
Fatigue Questionnaire (1 to 5-point scale x 10 questions for a total score range of 0 to 50) where a low value indicates less fatigued (better outcome) and a high value indicates more fatigued (worse outcome)
Time frame: through study completion, an average of 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tDCS and Fatigue | Fatigue Assessment Scale (FAS) | 31.32 Total score (1 to 5 point scale) | Standard Deviation 8.41 |
| Sham and Fatigue | Fatigue Assessment Scale (FAS) | 28.42 Total score (1 to 5 point scale) | Standard Deviation 6.41 |
| tDCS and Non-fatigue | Fatigue Assessment Scale (FAS) | 14.90 Total score (1 to 5 point scale) | Standard Deviation 3.63 |
| Sham and Non-fatigue | Fatigue Assessment Scale (FAS) | 15.3 Total score (1 to 5 point scale) | Standard Deviation 4.57 |
Fatigue Severity Scale (FSS)
Fatigue Questionnaire (1 to 7 point scale x 9 questions for a total score range of 0 to 63) with a low value indicating less severe fatigue (better outcome) and a high value indicating more severe fatigue (worse outcome)
Time frame: through study completion, an average of 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| tDCS and Fatigue | Fatigue Severity Scale (FSS) | 5.08 Total score (1-7 point scale) | Standard Deviation 1.6 |
| Sham and Fatigue | Fatigue Severity Scale (FSS) | 4.73 Total score (1-7 point scale) | Standard Deviation 1.14 |
| tDCS and Non-fatigue | Fatigue Severity Scale (FSS) | 2.13 Total score (1-7 point scale) | Standard Deviation 0.61 |
| Sham and Non-fatigue | Fatigue Severity Scale (FSS) | 1.98 Total score (1-7 point scale) | Standard Deviation 0.55 |