Low-Dose Sirolimus for Long COVID Syndrome

Overseen By Mackenzie Doerstling, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, ACE inhibitors, others

Disqualifiers: Autoimmune conditions, Chronic Lyme, Hepatic impairment, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Sirolimus to determine its effectiveness for individuals with Long COVID. Long COVID is a condition where symptoms such as fatigue, memory loss, or shortness of breath persist for months after a COVID-19 infection. The trial compares Sirolimus to a placebo (a pill with no active drug) to assess symptom improvement. Individuals officially diagnosed with Long COVID who experience moderate fatigue and post-exertional malaise may be suitable for this study. Participants must attend appointments in New York City. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interact with sirolimus, such as some antibiotics, antifungals, and other drugs that affect sirolimus levels. If you're on any of these, you might need to adjust your dose or stop them. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sirolimus, the treatment under study for Long COVID, has promising safety results from earlier studies. For example, in studies with hospitalized COVID-19 patients, sirolimus was generally well tolerated. Patients taking sirolimus had a lower risk of blood clots compared to those who took a placebo.

These findings suggest that sirolimus may be safe for people. However, larger studies are needed to confirm these results. Sirolimus is also already approved by the FDA for other uses, which provides some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Long COVID?

Unlike the standard of care for Long COVID, which often involves symptom management with medications like antihistamines and anti-inflammatories, sirolimus offers a novel approach. Sirolimus is an immunosuppressant that works by targeting and modulating the immune system, which may help address the underlying immune-related issues in Long COVID. Researchers are excited about sirolimus because its unique mechanism of action could potentially provide more effective relief by addressing the root causes of Long COVID symptoms rather than just alleviating them temporarily.

What evidence suggests that this trial's treatments could be effective for Long COVID?

Research has shown that sirolimus, also known as rapamycin, might improve symptoms in people with Long COVID. In this trial, participants will receive either low-dose sirolimus or a placebo. Sirolimus is believed to work by addressing mitochondrial dysfunction, as mitochondria are the parts of cells that produce energy. When mitochondria function poorly, it can cause fatigue, cognitive difficulties, and exercise intolerance—common issues in Long COVID. Early findings suggest that sirolimus might help by enhancing cellular energy production. While more research is needed, initial results are promising for sirolimus in easing Long COVID symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

David Putrino, PT, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with Long COVID, also known as Post-Acute Sequelae of COVID-19 (PASC), who are seeking treatment. Specific eligibility criteria details were not provided, so interested individuals should contact the study organizers for more information.

Inclusion Criteria

Provision of signed and dated informed consent form

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 specific symptoms following SARSCoV-2 infection, Participants who are willing and able to comply with all study procedures, Baseline EQ-VAS ≤70; EQ-VAS before the index infection ≥80

Exclusion Criteria

Pre-existing conditions impacting immunological profiling analysis, Pre-2020 diagnosis of another Post-Acute Infectious Syndrome, Documented history of vaccine injury, History of lung or liver transplant, Known hepatic or renal impairment, Weighing less than 40 kg, Current use of sirolimus, Taking medications with known interactions to sirolimus, Febrile illness within the last 3 months of planned baseline evaluation, Treatment with another investigational drug within 3 months of planned baseline evaluation, Uncontrolled diabetes, unstable ischemic heart disease, clinically significant underlying pulmonary disease, history of 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, Planning to be or are pregnant, Nursing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose sirolimus or placebo for up to 12 weeks

12 weeks

Regular visits for monitoring and dose escalation

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Post-treatment assessments at Week 12 and Week 24

What Are the Treatments Tested in This Trial?

Interventions

• Sirolimus

Trial Overview The trial is testing low-dose sirolimus against a placebo to see if it can help with Long COVID symptoms. It's a randomized and controlled study at Mount Sinai in New York, aiming to measure improvements based on patient-reported outcomes.

How Is the Trial Designed?

Group I: Low-dose sirolimus Experimental Treatment 1 Intervention

Participants will follow the escalation scheme and receive sirolimus for up to 12 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants will follow the escalation scheme and receive the placebo for up to 12 weeks.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

The Anlyan Center

Collaborator

PolyBio Research Foundation

Collaborator

Trials

3

Recruited

250+

PolyBio Research Foundation

Collaborator

Published Research Related to This Trial

A 14-day study of sirolimus in renal transplant patients showed that it can be safely combined with cyclosporine and corticosteroids, as it did not significantly affect kidney function or blood pressure.

While sirolimus caused a reversible decrease in platelet and white blood cell counts and increased cholesterol levels, these side effects were manageable and distinct from the nephrotoxic effects of cyclosporine, suggesting a potential for effective immunosuppression without added toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The side effect profile of sirolimus: a phase I study in quiescent cyclosporine-prednisone-treated renal transplant patients. Murgia, MG., Jordan, S., Kahan, BD.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06960928

Low Dose Sirolimus in People With Post-Acute Sequelae ... 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 ...

2. trialstoday.org trialstoday.org/trial/NCT06960928

Low Dose Sirolimus in People With Post-Acute Sequelae ... This study aims to evaluate the efficacy of Sirolimus in adults with Long COVID. Efficacy will be evaluated by measuring patient-reported ...

3. gethealthspan.com gethealthspan.com/research/article/rapamycin-treatment-for-long-covid?srsltid=AfmBOoqLqJzpmJjpNfpWWwnte1pRozIX4GcuYwbVeRm_bobKb9AL37sY

The Surprising Role of Rapamycin in Treating Long COVID ... Rapamycin and Mitochondrial Health: Mitochondrial dysfunction, a driver of fatigue, brain fog, and exercise intolerance in long COVID, stems ...

4. withpower.com withpower.com/trial/phase-3-covid-19-4-2025-c042e

Low-Dose Sirolimus for Long COVID Syndrome The trial is testing low-dose sirolimus against a placebo to see if it can help with Long COVID symptoms. It's a randomized and controlled study at Mount Sinai ...

5. polybio.org polybio.org/projects/long-covid-low-dose-rapamycin-clinical-trial/

Long COVID low-dose rapamycin clinical trial A double blinded randomized controlled pilot clinical trial to determine if low-dose rapamycin can improve symptoms in patients with long COVID.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12449737/

Safety and efficacy of sirolimus in hospitalised patients with ... There was a decreased risk of thromboembolic complications in patients on sirolimus compared with placebo. Conclusions: Larger studies are warranted to evaluate ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2212534524000029

Safety and efficacy of sirolimus in hospitalised patients with ... Our hypothesis was that treatment with sirolimus will be well tolerated and lead to improved clinical outcomes in hospitalised patients with COVID-19.

8. gethealthspan.com gethealthspan.com/research/article/rapamycin-treatment-for-long-covid?srsltid=AfmBOopiMPVy-T14dXYV8jt5pRDWS5gxRfdW2igkMO4ENgkMVys-6SRm

The Surprising Role of Rapamycin in Treating Long COVID ... Rapamycin and Mitochondrial Health: Mitochondrial dysfunction, a driver of fatigue, brain fog, and exercise intolerance in long COVID, stems ...

9. cell.com cell.com/cell/fulltext/S0092-8674(24)00886-9

Mechanisms of long COVID and the path toward therapeutics We review the current state of knowledge regarding the biology and pathophysiology of long COVID, focusing on how the proposed mechanisms explain the ...