Long COVID-19 Syndrome, Chronic Fatigue Syndrome
Conditions
Keywords
Long COVID-19 Syndrome, Fluvoxamine, Metformin, Adaptive Trial Design, Randomized Controlled Trial
Brief summary
Date of notification letter to the IRB informing start of recruitment activities: October 21, 2023. Long COVID is a multi-systemic condition comprising often severe and persistent symptoms (longer than 12 weeks) that follow a known episode of COVID-19 and cannot be explained by another medical condition. This condition is observed in up to 15% of all individuals after an acute episode of COVID-19, even in those who had a mild and oligosymptomatic SARS-CoV-2 infection. Around 40% of these patients present symptoms that significantly compromise their daily activities. There is increasing evidence that LONG COVID is accompanied by dysregulated, persistent and uncontrolled inflammation, often accompanied by the development of an autoreactive immune response, including autoantibodies. Symptoms can last months or years, particularly in cases of chronic fatigue syndrome, with significant proportions of individuals having significant chronic impairment, preventing the performance of work and social activities.
Detailed description
There is currently no approved therapies for Long COVID. Several clinical trials have been developed to address this clinical condition, however the results were based on small-scale pilot studies. We developed this adaptive, large-scale, prospective, double-blind clinical trial to evaluate the effect of chronic immune-inflammatory modulation on persistent Long-COVID symptoms.
Interventions
DRUGFluvoxamine Maleate 100 MG
Fluvoxamine Maleate 100 mg each pills
DRUGPlacebo
Placebo talc pills of same shape, color, weight if compared with active comparator
Metformin Extended release oral tablets of 750 mg each pill
Sponsors
Cardresearch
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The production of medication bottles is carried out by a pharmaceutical company, which does not have access to members of the research centers. The pills are similar in shape, color, size and weight and are packaged in identical bottles and coded according to each medication arm, this code being inaccessible to the investigator, the sponsor, the medical care provider and the research participant. The allocation process follows a random sequential distribution into blocks. The posology of the medications is identical for all arms.
Intervention model description
Multicenter, adaptive, randomized, double-blind, placebo-controlled, prospective, pharmacological intervention trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older at the time of screening. 2. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where approved locally and nationally). 3. Previous confirmed case of SARS-CoV-2 infection (e.g., reports having a positive nucleic acid amplification test or a professional-use SARS-CoV-2 rapid antigen diagnostic test or positive self-test). 4. Participants with a clinical picture compatible with LONG COVID according to international definitions: (www.nice.org.uk/guidance/ng188, https://www.who.int/publications/i/item/WHO-2019-nCoV-Post\_COVID -19\_condition-Clinical\_case\_definition-2021.1), and fatigue symptoms with an average score of at least 03 on the Fatigue Analog Scale (FSS) 5. Not currently hospitalized or requiring hospitalization, or having been hospitalized in an intensive care center at the time of the COVID-19 episode. 6. Participants with the following vital data: 1. Heart Rate between 55 and 100 bpm; 2. Temperature below 38o C; 3. Oxygen saturation ≥ 95%. 7. Patients of childbearing potential or with partners of childbearing potential must agree to use adequate contraception during the study and up to 90 days of follow-up. 8. The symptoms of fatigue cannot be attributed to any other cause (in the researcher's opinion). 9. Willingness to follow all study procedures.
Exclusion criteria
1. Known acute SARS-CoV-2 infection; 2. Inability to understand the content of the Informed Consent Form or to follow the study procedures; 3. Known previous diagnosis of malignant encephalomyelitis/chronic fatigue syndrome, unrelated to SARS-CoV-2 infection; 4. Known pre-existing dysautonomia, unrelated to SARS-CoV-2 infection; 5. Diabetes mellitus (
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement on Fatigue Severity Score Scale (FSS) | Day 60 after randomization | Improvement on Fatigue Severity Score Scale (FSS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement on Fatigue Severity Score Scale (FSS) | Day 30 after randomization | Improvement on Fatigue Severity Score Scale (FSS) |
| Reduction on any cause hospitalization | Day 60 after randomization | Reduction on any cause hospitalization |
| Safety of metformin | Since randomization up to Day 60 (last IMP dose) | Safety of metformin (intention to treat analysis) |
| Safety of Fluvoxamine | Since randomization up to Day 60 (last IMP dose) | Safety of Fluvoxamine (intention to treat analysis) |
| Death of any cause | Since randomization up to Day 60 (last IMP dose) | Occurrence of Death of any cause |
Countries
Brazil
Contacts
Primary ContactGilmar Reis, MD, PhD
Backup ContactMaria IC Simplicio, Pharm
Outcome results
None listed