Long COVID
Conditions
Keywords
lithium, long COVID
Brief summary
This study will assess low-dose lithium's effects on several different symptoms experienced by long COVID patients.
Detailed description
In this double-blind, placebo-controlled study, 50 patients with long COVID will be randomly assigned to either low-dose oral lithium or placebo therapy for three weeks. After the double-blind study phase, all patients will be provided with lithium therapy for two additional weeks. Study visits will occur at baseline and after the three-week double-blind study phase.
Interventions
DRUGLithium
Lithium has multiple mechanisms of action including anti-inflammatory actions, which may be relevant for treating long COVID.
DRUGPlacebo
Inactive pill
Sponsors
National Center for Advancing Translational Sciences (NCATS)
State University of New York at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Documented or self-reported positive test for COVID-19 ≥4 weeks prior to enrollment. 2. No fever for ≥4 weeks prior to enrollment. 3. Reports fatigue and/or brain fog (i.e. concentration or memory impairment) for ≥4 weeks prior to enrollment on the PASC-Specific Symptom questionnaire beginning after infection with COVID-19. 4. Fatigue Severity Scale (FSS) score ≥28 or Brain Fog Severity Scale (BFSS) score ≥28 at baseline. 5. Beck Depression Inventory II score \<24. 6. No change in any psychoactive or steroid medications for ≥30 days. 7. No plan to change any psychoactive, steroid or diuretic medication for ≥5 weeks and not planning on obtaining a COVID vaccine within the next 5 weeks. 8. Not using any long COVID therapies felt to be worsening the patient's symptoms or starting a long COVID therapy within the next 5 weeks. 9. No history of fibromyalgia, chronic fatigue syndrome or progressive cognitive disorder prior to COVID-19 infection. 10. No active medical, psychiatric or social problems that would interfere with completing the study procedures in the opinion of the investigator. 11. No use of tobacco or marijuana products for \>6 months and no current alcohol abuse (≥4 drinks/day) or illicit drug use. 12. Not receiving or applying for disability payments or workman's compensation for long COVID. 13. Not pregnant or nursing or planning to get pregnant over the next two months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue Severity Scale | Change from baseline to day 21 | 7-item questionnaire assessing fatigue severity. Score range 1-49 with higher values signifying worse outcome |
| Brain Fog Severity Scale | Change from baseline to day 21 | 7-item questionnaire assessing brain fog severity. Score range 1-49 with higher values signifying worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Short Form-12 Health Survey (1-week Modification) | Change from baseline to day 21 | Quality of life assessment over past week, PCS-subscale. 12-item quality of life scale. Score range 0-100 for both the Physical Component Score and the Mental Component Score with higher values signifying better outcomes. |
| Desire to Continue Therapy | Day 21 | Single Yes/No question. Single-item scale. Score range 1-2 with higher value signifying better outcome. Reported as % of respondents recording yes. |
| Generalized Anxiety Disorder-2 Scale | Change from baseline to day 21 | 2-item questionnaire assessing anxiety frequency over the past week. 2-item scale. Score range 0-6 with higher values signifying worse outcome |
| Headache and Body Pain Bother Scale | Change from baseline to day 21 | 2-item questionnaire assessing frequency of headaches and body pain over the past week, Headache score. 2-item scale. Score range 2-10 with higher values signifying worse outcome |
| Patient Global Impression of Change (PGIC) | Day 21 | Change in symptoms on 7-point scale. Single-item scale. Score range 1-7 with higher values signifying better outcome |
| Sense of Smell and Taste Change Scale | Day 21 | Subjective change from baseline on a 7-point scale (score range: 1-7) with higher scores indicating better outcomes. Scores of 1 and 7 indicate sense of smell and taste were very much worse or very much improved, respectively, since the start of study treatment. |
| Digit Symbol Substitution Test | Change from baseline to day 21 | Validated cognitive test. Score range 0-100 with higher scores indicating a better outcome. |
| Delayed Recall Test | Change from baseline to day 21 | Validated cognitive test. Score range 0-5 with higher scores indicating better outcomes. |
| Insomnia Severity Index | Change from baseline to day 21 | 7-item questionnaire assessing insomnia severity over the past week. 7-item scale. Score range 0-28 with higher values signifying worse outcome. |
| Well-Being Scale | Change from baseline to day 21 | Sense of well-being over past week on 10-point scale. Score range 0-10 with higher values signifying better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lithium Lithium 10mg po qd
Lithium: Lithium has multiple mechanisms of action including anti-inflammatory actions, which may be relevant for treating long COVID. | 24 |
| Placebo Placebo identically matching the lithium pills
Placebo: Inactive pill | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Lithium | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 6 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 20 Participants | 33 Participants |
| Age, Continuous | 62.3 years STANDARD_DEVIATION 14.3 | 55.0 years STANDARD_DEVIATION 13.7 | 58.5 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 26 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 26 Participants | 50 Participants |
| Region of Enrollment United States | 24 Participants | 26 Participants | 50 Participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 26 |
| other Total, other adverse events | 0 / 24 | 0 / 26 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 |
Outcome results
Primary
Brain Fog Severity Scale
7-item questionnaire assessing brain fog severity. Score range 1-49 with higher values signifying worse outcome
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Brain Fog Severity Scale | -9.0 score on a scale | Standard Deviation 13.8 |
| Placebo | Brain Fog Severity Scale | -8.1 score on a scale | Standard Deviation 10.6 |
p-value: 0.79t-test, 2 sided
Primary
Fatigue Severity Scale
7-item questionnaire assessing fatigue severity. Score range 1-49 with higher values signifying worse outcome
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Fatigue Severity Scale | -11.3 score on a scale | Standard Deviation 12.6 |
| Placebo | Fatigue Severity Scale | -8.6 score on a scale | Standard Deviation 12.3 |
p-value: 0.46t-test, 2 sided
Secondary
Delayed Recall Test
Validated cognitive test. Score range 0-5 with higher scores indicating better outcomes.
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Delayed Recall Test | 0.46 score on a scale | Standard Deviation 1.02 |
| Placebo | Delayed Recall Test | 0.35 score on a scale | Standard Deviation 0.8 |
p-value: 0.35t-test, 2 sided
Secondary
Desire to Continue Therapy
Single Yes/No question. Single-item scale. Score range 1-2 with higher value signifying better outcome. Reported as % of respondents recording yes.
Time frame: Day 21
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lithium | Desire to Continue Therapy | 12 Participants |
| Placebo | Desire to Continue Therapy | 13 Participants |
p-value: 1Barnard unconditional exact test
Secondary
Digit Symbol Substitution Test
Validated cognitive test. Score range 0-100 with higher scores indicating a better outcome.
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Digit Symbol Substitution Test | 4.3 score on a scale | Standard Deviation 5.9 |
| Placebo | Digit Symbol Substitution Test | 6.6 score on a scale | Standard Deviation 9 |
p-value: 0.29t-test, 2 sided
Secondary
Generalized Anxiety Disorder-2 Scale
2-item questionnaire assessing anxiety frequency over the past week. 2-item scale. Score range 0-6 with higher values signifying worse outcome
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Generalized Anxiety Disorder-2 Scale | -0.8 score on a scale | Standard Deviation 1.7 |
| Placebo | Generalized Anxiety Disorder-2 Scale | -1.4 score on a scale | Standard Deviation 1.7 |
p-value: 0.28t-test, 2 sided
Secondary
Headache and Body Pain Bother Scale
2-item questionnaire assessing frequency of headaches and body pain over the past week, Headache score. 2-item scale. Score range 2-10 with higher values signifying worse outcome
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Headache and Body Pain Bother Scale | -0.6 score on a scale | Standard Deviation 0.7 |
| Placebo | Headache and Body Pain Bother Scale | -0.7 score on a scale | Standard Deviation 1.2 |
p-value: 0.58t-test, 2 sided
Secondary
Insomnia Severity Index
7-item questionnaire assessing insomnia severity over the past week. 7-item scale. Score range 0-28 with higher values signifying worse outcome.
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Insomnia Severity Index | -6.0 score on a scale | Standard Deviation 6.7 |
| Placebo | Insomnia Severity Index | -4.4 score on a scale | Standard Deviation 4.8 |
p-value: 0.41t-test, 2 sided
Secondary
Patient Global Impression of Change (PGIC)
Change in symptoms on 7-point scale. Single-item scale. Score range 1-7 with higher values signifying better outcome
Time frame: Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Patient Global Impression of Change (PGIC) | 4.7 score on a scale | Standard Deviation 1.1 |
| Placebo | Patient Global Impression of Change (PGIC) | 4.6 score on a scale | Standard Deviation 1.2 |
p-value: 0.68t-test, 2 sided
Secondary
Sense of Smell and Taste Change Scale
Subjective change from baseline on a 7-point scale (score range: 1-7) with higher scores indicating better outcomes. Scores of 1 and 7 indicate sense of smell and taste were very much worse or very much improved, respectively, since the start of study treatment.
Time frame: Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Sense of Smell and Taste Change Scale | 4.1 score on a scale | Standard Deviation 0.3 |
| Placebo | Sense of Smell and Taste Change Scale | 4.2 score on a scale | Standard Deviation 0.4 |
p-value: 0.5t-test, 2 sided
Secondary
Short Form-12 Health Survey (1-week Modification)
Quality of life assessment over past week, PCS-subscale. 12-item quality of life scale. Score range 0-100 for both the Physical Component Score and the Mental Component Score with higher values signifying better outcomes.
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Short Form-12 Health Survey (1-week Modification) | 5.1 score on a scale | Standard Deviation 8.5 |
| Placebo | Short Form-12 Health Survey (1-week Modification) | 4.2 score on a scale | Standard Deviation 11.1 |
p-value: 0.75t-test, 2 sided
Secondary
Well-Being Scale
Sense of well-being over past week on 10-point scale. Score range 0-10 with higher values signifying better outcome.
Time frame: Change from baseline to day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lithium | Well-Being Scale | 1.0 score on a scale | Standard Deviation 2 |
| Placebo | Well-Being Scale | 0.9 score on a scale | Standard Deviation 2.1 |
p-value: 0.89t-test, 2 sided