Table 3.

Clinical trials of drugs or dietary supplements on Long COVID completed by 24 November, 2022 (ClinicalTrials.gov database)*

	NCT number	Title	Aim	Interventions	Study design	Population	Results
1	NCT04871815	Effects of Sodium Pyruvate Nasal Spray in COVID-19 Long Haulers	To examine the effects of N115 (Sodium pyruvate nasal spray) treatment on the symptoms associated with COVID-19 Long Haulers	Drug: sodium pyruvate nasal spray	Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment	Enrollment: 22 Age: 18 Years to 40 Years (Adult) Sex: All	Primary outcome data are available
2	NCT04795557	Efficacy of Adaptogens in Patients With Long COVID-19	To demonstrate possible efficacy of adjuvant treatment with ADAPT-232 in decreasing the duration of the convalescence, alleviation of fatigue, headache, attention deficit, difficult and rapid respiration, depression, anxiety and other symptoms of Long COVID-19 during rehabilitation period	Dietary Supplement: ADAPT-232 oral solution Other: Placebo oral solution	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment	Enrollment: 100 Age: 18 Years and older (Adult, Older Adult Sex: All	No results
3	NCT04880161	A Study to Evaluate Ampion in Patients With Prolonged Respiratory Symptoms Due to COVID-19 (Long COVID)	To evaluate the safety of Ampion (low molecular weight filtrate of human serum albumin with the in vitro ability to modulate inflammatory cytokine levels) and the clinical outcomes in patients with Long COVID	Biological: Inhaled Ampion Other: Inhaled Placebo	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment	Enrollment: 32 Age: 18 Years and older (Adult, Older Adult) Sex: All	Results Submitted, but is not yet publicly available
4	NCT05311852	Effects of PEA-LUT on Frontal Lobe Functions and GABAergic Transmission in Long-Covid Patients	To test the possible therapeutic effects of an 8-week therapy with PEA-LUT on GABAB-ergic neurotransmission, LTP-like synaptic plasticity, indexed with transient potentiation of motor evoked potentials (MEP) amplitude after repetitive TMS given as intermittent theta burst stimulation (iTBS) in Long COVID patients with cognitive complaints and fatigue	Dietary Supplement: palmitoylethanolami co-ultramicronized with antioxidant flavonoid luteolin (PEA-LUT) Dietary Supplement: Placebo	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment	Enrollment: 34 Age: 18 Years and older (Adult, Older Adult) Sex: All	No results
5	NCT04828668	Study to Evaluate Benefits and Safety of Endourage Formula C™ Oral Drops in People With Post-Acute COVID-19 Syndrome	To evaluate the clinical benefits of Formula C on symptoms in adults who have documented PACS or persistence of effects consistent with COVID-19 and to assess the impact of Formula C on quality-of-life (QOL) in persons with PACS. The secondary objective was to assess the safety of Formula C in persons with PACS	Dietary Supplement: Targeted Wellness Formula C™ Sublingual Drops- 1200 mg–30 mL (Formula C) Dietary Supplement: Placebo	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Single (Participant) Primary Purpose: Other	Enrollment: 32 Age: 18 Years to 75 Years (Adult, Older Adult) Sex: All	Given that both groups demonstrated improvement, both formulations may be contributing to these findings. Limitations include the small number of participants, the lack of a true placebo, and limited time on study products (Young et al. 2022)
6	NCT05152849	Efficacy, Safety, Tolerability of AXA1125 in Fatigue After COVID-19 Infection	To compare the effects of AXA1125, an orally active mixture of amino acids, compared to placebo, on improving muscle function (metabolism) following moderate exercise in subjects with fatigue-Predominant Post-Acute Sequelae of SARS-CoV-2 as well as the safety and tolerability of AXA1125. Subjects will take one dose of AXA1125 or a placebo twice daily for 28 days	Drug: AXA1125 Drug: Placebo	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment	Enrollment: 41 Age: 18 Years to 64 Years (Adult) Sex: All	No results
7	NCT04652518	LYT-100 in Post-acute COVID-19 Respiratory Disease	To evaluate the Safety and Efficacy of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease	Drug: LYT-100 Other: Placebo	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Investigator, Outcomes Assessor) Primary Purpose: Treatment	Enrollment: 185 Age: 18 Years to 80 Years (Adult, Older Adult) Sex: All	No results
8	NCT04960215	Coenzyme Q10 as Treatment for Long Term COVID-19	To investigate the effect of high-dose Coenzyme Q10 on number and severity of self-reported symptoms in patients with Long Term COVID-19	Drug: Coenzyme Q10 Drug: Placebo	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment	Enrollment: 121 Age: 18 Years and older (Adult, Older Adult) Sex: All	No results
9	NCT04699097	The Effect of Azithromycin Use on Conduction System of Heart in COVID-19 Positive Children	To evaluate the effect of Azithromycin on ventricular repolarization in COVID-19 positive pediatric patients	Drug: Azithromycin	Observational Model: Case-Only Time Perspective: Prospective	Enrollment: 105 Age: 1 Year to 18 Years (Child, Adult) Sex: All	No results
10	NCT04814914	An observational clinical study to evaluate COVID-19 symptoms in “Long Hauler” patients who participated in K031-120 or K032-120	To evaluate the presence of symptoms of COVID-19 infection in patients who participated in K031-120 or K032-120 (“long hauler”)	Other: KB109 is a novel glycan + Self Supportive Care Other: Self Supportive Care (SSC) Alone	Observational Model: Cohort Time Perspective: Prospective	Enrollment: 333 Age: 18 Years and older (Adult, Older Adult) Sex: All	No results
11	NCT04382755	Zilucoplan® in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure	The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post-COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury	Drug: Zilucoplan® Drug: Placebo	Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment	Enrollment: 81 Age: 18 Years and older (Adult, Older Adult) Sex: All	Complement C5 inhibition with zilucoplan led to numerically relevant respiratory and clinical improvements in hypoxemic COVID-19 patients with systemic inflammation, Zilucoplan lowered serum C5b-9 (p < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified (De Leeuw et al. 2022)
12	NCT04678830	COVID-19 Long-Haulers Study	To assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injections in subjects experiencing prolonged symptoms (> 12 weeks) of COVID-19	Drug: Placebos Drug: Leronlimab (700 mg)	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment	Enrollment: 56 Age: 18 Years and older (Adult, Older Adult) Sex: All	The mean symptom score changes from baseline to the latest available time point from day 30–56 for leronlimab vs placebo were –16.0 and –12.0, respectively; adjusting for prespecified covariates, the adjusted mean difference was –1.0 (not statistically significant). For several symptoms, there was a numerically higher percentage of participants with reduced raw symptom scores for leronlimab compared with placebo treatment reaching borderline statistical significance without correction for multiple comparisons due to the exploratory nature of this pilot study (Gaylis et al. 2022)

*In the ClinicalTrials.gov database, 326 results were found for the keywords Long COVID, of which 58 trials studies were completed on 24.11.2022. Out of the completed trials, 15 involved the use of a drug or dietary supplements. 3 studies related to acute therapy, these were not relevant from the point of view of Long COVID