Low-dose sirolimus for adults with Long COVID (PASC)

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

This trial will test whether low-dose sirolimus can reduce symptoms in adults who have had Long COVID for at least six months.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (Academic / other)
• Locations: 1 site (New York, New York)
• Trial ID: NCT06960928 on ClinicalTrials.gov

What this trial studies

This is a phase 3, randomized, placebo-controlled, multi-ascending trial conducted at the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York. Adults with physician-diagnosed Long COVID of at least six months duration who meet symptom thresholds for fatigue and post-exertional malaise are randomized to low-dose sirolimus or placebo. The study uses patient-reported outcome measures to determine symptomatic benefit over the treatment period and includes scheduled clinic visits and laboratory monitoring. The intervention is given off-label under an IND-exempt protocol with safety and efficacy comparisons between the two arms.

Who should consider this trial

Good fit: Adults aged 18 or older with a physician diagnosis of Long COVID, at least six months of qualifying symptoms including moderate fatigue and post-exertional malaise, and who can attend all Mount Sinai study visits are ideal candidates.

Not a fit: People with less than six months since acute infection, without moderate fatigue or PEM, or with contraindications to sirolimus are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, low-dose sirolimus could lessen fatigue and other persistent Long COVID symptoms and improve daily functioning.

How similar studies have performed: Use of mTOR inhibitors like sirolimus for Long COVID is largely novel with limited prior clinical data, though there is some mechanistic rationale from other conditions.

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

Where this trial is running

New York, New York

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: David Putrino, PT, PhD — Icahn School of Medicine at Mount Sinai
• Study coordinator: David Putrino, PT, PhD

Conditions Long COVID-19; Post-Acute Sequelae of COVID-19; Sirolimus; Rapamycin