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

NCT06960928 | Recruiting Phase 3 FDA Drug

• 1 other identifier: STUDY-24-01366
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Long COVID-19

Keywords

Long COVID-19; Post-Acute Sequelae of COVID-19 (PASC); Sirolimus; Rapamycin

Outcome Measures

Primary Outcomes (1)

• European Quality of Life-Visual Analogue Scale (EQ-VAS)

  The EQ VAS records the patient's self-rated health on a visual analogue scale where the endpoints are labelled 'The best health you can imagine' (100) and 'The worst health you can imagine' (0), with higher scores indicating better health state. The VAS can be used as a quantitative measure of health outcome that reflects the patient's own judgement.

  Baseline (Week 0) and Post-treatment (Week 12 and Week 24)

Secondary Outcomes (14)

• The EuroQol Five-Dimensional Health Questionnaire (EQ-5D-5L)

  Baseline (Week 0) and Post-treatment (Week 12 and Week 24)

• Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29)

  Baseline (Week 0) and Post-treatment (Week 12 and Week 24)

• General Symptom Questionnaire (GSQ-30)

  Baseline (Week 0) and Post-treatment (Week 12 and Week 24)

• Patient Health Questionnaire (PHQ-9)

  Baseline (Week 0) and Post-treatment (Week 12 and Week 24)

• Generalized Anxiety Disorder (GAD-7)

  Baseline (Week 0) and Post-treatment (Week 12 and Week 24)

Study Arms (2)

Low-dose sirolimus

EXPERIMENTAL

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

Drug: Low-dose sirolimus

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Low-dose sirolimus DRUG

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)

Also known as: rapamycin

Low-dose sirolimus

Placebo DRUG

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)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• PolyBio Research Foundation: collaborator
• The Anlyan Center: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• David Putrino, PT, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Putrino, PT, PhD

CONTACT

212-241-7658; coreresearch@mountsinai.org

Mackenzie Doerstling, MPH

CONTACT

212-241-7658; coreresearch@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: May 7, 2025
• Study Start: April 18, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: July 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)