Low Dose Sirolimus in People With Post-Acute Sequelae of COVID-19 (PASC) Long COVID-19

Overview

The study is conducted in New York, New York at The Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai. This is an IND-exempt, off-label, multi-ascending, randomized, placebo-controlled clinical trial of sirolimus (also known as rapamycin) in adults with Long COVID. There are 2 arms: Sirolimus and Placebo. This study aims to evaluate the efficacy of Sirolimus in adults with Long COVID. Efficacy will be evaluated by measuring patient-reported outcomes in response to Sirolimus.

Interventions

• Drug Low-dose sirolimus
  Participants will take sirolimus, at home, for 12 weeks (3 months). * 1 pill once a week for 2 weeks (1mg) * 2 pills once a week for 2 weeks (2mg) * 4 pills once a week for 8 weeks (4mg)
• Drug Placebo
  Participants will take a matching placebo, at home, for 12 weeks (3 months). * 1 pill once a week for 2 weeks (0mg) * 2 pills once a week for 2 weeks (0mg) * 4 pills once a week for 8 weeks (0mg)

Primary outcome measures

• European Quality of Life-Visual Analogue Scale (EQ-VAS) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]

Secondary outcome measures (12)

• The EuroQol Five-Dimensional Health Questionnaire (EQ-5D-5L) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• General Symptom Questionnaire (GSQ-30) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Patient Health Questionnaire (PHQ-9) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Generalized Anxiety Disorder (GAD-7) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Neuro-QoL™ v2.0 Cognitive Function-Short Form [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Single-item Sleep Quality Scale (SQS) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]]
• Fatigue Severity Scale [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Fatigue Visual Analogue Scale [F-VAS]) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• DePaul Post-Exertional Malaise Questionnaire (DSQ) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Composite Autonomic Symptom Score 31(COMPASS-31) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
• Pain (P-VAS) [Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated informed consent form
• Any sex, aged 18+
• Must be able to attend all study visits located at 5 East 98th St, New York, NY
• Diagnosed with:

• Long COVID

• Documented clinical history of confirmed or suspected acute SARS-CoV-2 infection a minimum of 6 months prior to contact with the study team
• Formal diagnosis of Long COVID from a physician
• At least a six-month history of one of the following symptoms following SARSCoV-2 infection:

• headache, memory loss, insomnia, mood disturbance, chest pain, palpitations, shortness of breath, cough, muscle pains, joint pains, or GI upset
• AND at least moderate fatigue (measured by Fatigue Severity Score)
• AND at least moderate post-exertional malaise (PEM) (measured by DePaul PEM screener)
• Participants who are willing and able to comply with all data collection, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Baseline EQ-VAS ≤70; EQ-VAS before the index infection ≥80 (this information is collected before randomization as part of the baseline survey)

Exclusion criteria

• Pre-existing conditions including, but not limited to:

• Autoimmune conditions such as Chronic EBV, Multiple Sclerosis, Hashimoto's Disease, etc. which would impact the immunological profiling analysis.
• A pre-2020 diagnosis of another Post-Acute Infectious Syndrome such as Chronic Lyme disease, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, etc.
• Documented history of vaccine injury
• History of lung or liver transplant
• Known hepatic or renal impairment
• Weighing less than 40 kg
• Or any other chronic condition that has the potential to impact on immunological profiling, at the discretion of the research physician
• Current use of sirolimus
• Taking a medication with known interactions to sirolimus:

• Strong CYP3A4 Inhibitors - clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir, such that dose reduction may be necessary
• Strong CYP3A4 Inducers - carbamazepine, dexamethasone, ethosuximide, glucocorticoids, griseofulvin, phenytoin, primidone, progesterone, rifabutin, rifampin, nafcillin, nelfinavir, nevirapine, oxcarbazepine, phenobarbital, phenylbutazone, rofecoxib (mild), St John's wort, sulfadimidine, sulfinpyrazone, troglitazone, and grapefruit, such that dose increase may be necessary.
• Drugs that may increase concentration when given with sirolimus - Verapamil, such that dose reduction may be necessary
• Other drugs that have the potential to increase sirolimus blood concentrations include (but are not limited to): fluconazole, clotrimazole, troleandomycin, nicardipine, cisapride, and metoclopramide
• Concomitant use of angiotensin-converting enzyme (ACE) inhibitors may increase the risk of developing angioedema.
• Febrile illness within the last 3 months of planned baseline evaluation
• Treatment with another investigational drug or other investigational intervention within 3 months of planned baseline evaluation
• Prophylactic use of aspirin (325 mg daily) for cardiovascular indications will be permitted in participants. All other medications for chronic medical conditions should be initiated at least two months prior to enrollment.
• Uncontrolled diabetes, unstable ischemic heart disease, clinically significant underlying pulmonary disease, history of an immunodeficiency or receiving immunosuppressive therapy; history of coagulopathy or medication condition requiring long-term anticoagulation; history of hepatic impairment; taking angiotensin-converting enzyme (ACE) inhibitors
• Participants who are planning to be or are pregnant
• Participants who are nursing

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Icahn School of Medicine at Mount Sinai — New York

Identifiers

NCT: NCT06960928 · STUDY-24-01366

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗