Table 2.

Ongoing trials on interventions for neurological symptoms of long COVID.

		Population Characteristics
Trial Registration Number/Country	Study Design	Recruitment Target (n), Age Range (Years)	Definition of Long COVID	Method of Acute COVID-19 Diagnosis	Comorbidities	Intervention	Comparator	Neurological Outcomes
NCT0557666 United States	Randomized double blind	200, >18	Post-COVID-19 symptoms persisting greater than three months with at least two post-COVID symptoms of moderate or severe intensity	Self-reported history of confirmed COVID-19 infection preceding post-COVID symptoms	Excluded individuals with severe liver disease, HIV infection, suspected or confirmed pregnancy or breastfeeding, or other medical conditions that would compromise patient’s safety or compliance	Nirmatrelvir with Ritonavir (Paxlovid)	Placebo with Ritonavir	Severity of brain fog, PROMIS cognitive function abilities score
NCT05430152 Canada	Randomized double blind	160, 19–69	Symptoms lasting three to six months post-acute infection	Positive test result or clinical confirmation by a physician	Excluded participants with any use of opioid medications	Low dose naltrexone	Placebo	Changes in fatigue intensity score, pain severity score, and symptom severity score
NCT05597722 United States	Randomized open label	120, 21–65	COVID-symptoms that persist three months or longer and a moderate cognitive impairment (MOCA) score ≤18 for at least three months	Positive PCR or home antigen test	Excluded individuals with pre-existing cardiac or kidney condition, severe hypertension, glaucoma, hyperthyroidism, and advanced arteriosclerosis	Dextroamphetamine-Amphetamine	Stimulant medication	Changes in cognitive impairment
NCT0494412 United States	Randomized quadruple blind	70, 18–75	Confirmed SARS-CoV-2 infection by PCR at least 24 weeks prior to baseline with a raw score of at least a score of 21 on PROMIS Fatigue SF 7a at screening	Laboratory-confirmed SARS-CoV-2 PCR test	Excluded individuals with orthostatic hypertension, tachycardia, use of sedating medications, lab abnormalities that may cause fatigue, history of anaphylaxis, previous chronic fatigue syndrome, previous fibromyalgia, previous lupus, previous Sjogren’s syndrome, or diagnosis of sleep apnea	RSLV-132	Placebo	PROMIS fatigue 7a T-score, FACIT fatigue questionnaire, severity of brain fog, performance on concentration task
NCT05350774 United States	Randomized double blind	60, >18	Persistent neurological symptoms exceeding 12 weeks from acute infection	Patient reported positive antigen test for SARS-CoV-2 followed by confirmatory nucleocapsid antibody testing or a positive SARS-CoV-2 PCR test result	Excluded individuals with ventricular arrhythmias, coronary artery disease, or a condition prior to COVID-19 infection that would confound interpretation	IV immunoglobulin, IV methylprednisone	Placebo	Proportion of participants with clinically meaningful improvement in the Health Utilities Index Mark 3 (HUI3) four weeks after start of study
NCT0561858 United States	Randomized quadruple blind	50, 18–80	Reported fatigue and/or brain fog for less than four weeks prior to enrollment on questionnaire after SARS-CoV-2 infection	Documented or self-reported positive test for COVID-19 less than four weeks prior to enrollment	Excluded individuals with current alcohol abuse, history of fibromyalgia, chronic fatigue syndrome, or progressive cognitive disorder, any active medical, psychiatric, or social problems that would interfere with study procedure, or use of any tobacco, marijuana, or illicit drug products	Lithium	Placebo	Severity of brain fog, frequency of anxiety, frequency of headaches, severity of insomnia, change in sense of smell and taste, and performance on cognitive tests
NCT05104424 Saudi Arabia	Randomized open label	44, >18	Unclear	Unclear	Excluded patients with any nasal deviation, congenital anomalies, or allergic sinusitis	Intranasal insulin, zinc, gabapentin, ice cube stimulation	Zinc only	Improvements in hyposmia (Sniffin Sticks test), dysgeusia, and self-assessment of hyposmia (Dynachron-olfaction questionnaire)
NCT04997395 United Kingdom	Open Label	12, ≥18	Confirmed by GP triage clinic and assessment by a long COVID clinic. Participant undertook the clinical assessment and investigations as recommended by the NICE guidance on long COVID	Unclear	Excluded individuals with ongoing mental and/or psychiatric illnesses/disorders that require active treatment during the trial period, use of anti-coagulant drugs, use of cannabinoids or cannabinoid-based medicine within three months prior to study, known dependence on cannabis, alcohol, or any other drug, history of chronic liver failure, history of allergy to tree nuts	MediCabilis Cannabis sativa 50	Discontinuing cannabidiol for three-weeks following 21 week period of taking cannabidiol	Changes in cognition, fatigue, self-reported quality of life, pain score, and anxiety/depression