Effect of Lithium Therapy on Long COVID Symptoms

Effect of Low-dose Lithium Therapy on Long COVID Symptoms: a Randomized Controlled Trial.

This study will assess low-dose lithium's effects on several different symptoms experienced by long COVID patients.

Study Overview

• Status: Completed
• Conditions: Long COVID
• Intervention / Treatment: Drug: Lithium; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Williamsville, New York, United States, 14221
      • University at Buffalo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lithium; Lithium 10mg po qd	Drug: Lithium; Lithium has multiple mechanisms of action including anti-inflammatory actions, which may be relevant for treating long COVID.
Placebo Comparator: Placebo; Placebo identically matching the lithium pills	Drug: Placebo; Inactive pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Severity Scale	7-item questionnaire assessing fatigue severity. Score range 1-49 with higher values signifying worse outcome	Change from baseline to day 21
Brain Fog Severity Scale	7-item questionnaire assessing brain fog severity. Score range 1-49 with higher values signifying worse outcome	Change from baseline to day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 21
Well-Being Scale	Sense of well-being over past week on 10-point scale. Score range 0-10 with higher values signifying better outcome.	Change from baseline to day 21
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.	Change from baseline to day 21
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".	Day 21
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	Change from baseline to day 21
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	Change from baseline to day 21
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.	Change from baseline to day 21
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.	Day 21
Digit Symbol Substitution Test	Validated cognitive test. Score range 0-100 with higher scores indicating a better outcome.	Change from baseline to day 21
Delayed Recall Test	Validated cognitive test. Score range 0-5 with higher scores indicating better outcomes.	Change from baseline to day 21

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Thomas Guttuso, Jr., MD, University at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Actual): July 21, 2023
• Study Completion (Actual): July 21, 2023

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: lithium, long COVID
• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Post-Acute COVID-19 Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antimanic Agents; Lithium Carbonate
• Other Study ID Numbers: STUDY00006678; UL1TR001412 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No