Long COVID-19Phase 3NCT06960928
Low Dose Sirolimus in People With Post-Acute Sequelae of COVID-19 (PASC) Long COVID-19
A Phase 3 study testing Low-dose sirolimus in people with Long COVID-19, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Long COVID-19
- What is being tested?
- Low-dose sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Apr 2025to 31 May 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Mackenzie Doerstling, MPH, CoreResearch@mountsinai.com
David Putrino, PT, PhD
About this study
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
- Being tested
- Low-dose sirolimus, Placebo
- Keywords
- Long COVID-19, Post-Acute Sequelae of COVID-19 (PASC), Sirolimus, Rapamycin
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose sirolimusDrug
Also called rapamycin
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)
PlaceboDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Low-dose sirolimus | Experimental | Participants will follow the escalation scheme and receive sirolimus for up to 12 weeks. Receives: Drug: Low-dose sirolimus |
| Placebo | Placebo comparator | Participants will follow the escalation scheme and receive the placebo for up to 12 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Secondary outcomes (14)
The EuroQol Five-Dimensional Health Questionnaire (EQ-5D-5L)
The EQ-5D-5L is a validated, standardized, generic instrument that is a preference-based health- related quality of life questionnaire. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. Full scale from 5 to 25, with higher score indicating poorer health outcomes.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29)
The PROMIS-29 v2.0 profile assesses pain intensity using a single 0-10 numeric rating item and seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) using four items per domain. The values of all item responses are averaged to generate subscores for each dimension. From these subscores, a global physical health score and a global mental health score are generated. The scores are translated into T-scores according to a reference population with a mean of 50 and a standard deviation of 10.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
General Symptom Questionnaire (GSQ-30)
The General Symptom Questionnaire-30 (GSQ-30) is a valid and reliable instrument to assess symptom burden among patients with acute and post-treatment. The GSQ-30 total score ranges from 0 to 120, with higher scores indicating a greater symptom burden.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Patient Health Questionnaire (PHQ-9)
The PHQ-9 is a series of questions assessing presence and severity of depression symptoms. It evaluates each of the DSM-IV depression criteria and scores the responses from 0 ("Not at all") to 3 ("Nearly every day"). PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Full scale from 0-27, with higher score indicating more severe symptoms.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Generalized Anxiety Disorder (GAD-7)
The GAD-7 is a 7-item scale developed and validated to identify generalized anxiety disorder and its severity. It assesses the frequency of 7 anxiety symptoms and scores the responses from 0 ("Not at all") to 3 ("Nearly every day"). Total scores of 5, 10, and 15 correspond to mild, moderate, and severe generalized anxiety disorder, respectively. Full scale from 0-21, with higher score indicating more symptoms.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Neuro-QoL™ v2.0 Cognitive Function-Short Form
The Neuro-QoL Cognitive Function v2.0 short form assesses perceived difficulties in cognitive abilities, including memory, attention, decision making, planning, organizing, calculating, remembering, and learning. The short form consists of 8 questions assessed on a 5-point Likert scale, resulting in a raw score range of 8 to 40. A raw score is then converted to a T-score using conversion tables. Scores 0.5 - 1.0 SD worse than the mean (T-score 40-45) = mild symptoms/impairment. Scores 1.0 - 2.0 SD worse than the mean (T-score 30-40) = moderate symptoms/impairment. Scores 2.0 SD or more worse than the mean (T-score below 30) = severe symptoms/impairment.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Single-item Sleep Quality Scale (SQS)
The SQS is a visual analog scale that instructs respondents to rate their overall quality of sleep over a 7-day recall period from 0 to 10. Scores of 0, 1, 4, 7, and 10 correspond to terrible, poor, fair, good, and excellent, respectively. Higher scores indicate better sleep quality.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
Fatigue Severity Scale
The Fatigue Severity Scale (FSS) uses a 7-point scale (1-7) to assess fatigue, with higher scores indicating greater severity, and a total score ranging from 9 to 63. Higher scores indicate more severe fatigue.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Fatigue Visual Analogue Scale [F-VAS])
The F-VAS consists of 18 items related to fatigue and energy in a visual analogue scale from 0 to 100. A higher score indicates more fatigue.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
DePaul Post-Exertional Malaise Questionnaire (DSQ)
The DSQ is designed to evaluate 54 classic ME/CFS symptoms, including fatigue, post-exertional malaise, sleep, pain, neurological/cognitive impairments, and autonomic, neuroendocrine, and immune symptoms. Each symptom's frequency and intensity are rated on a 5-point scale (0-4). Frequency and severity scores are multiplied by 25, added together, and then divided by 2 to create a composite frequency/severity score for each symptom. These scores range from 0 to 100, with higher scores indicating a greater symptom burden.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Composite Autonomic Symptom Score 31(COMPASS-31)
The COMPASS-31 is a 31-question self-assessment instrument of autonomic symptoms and function that is up-to-date, broadly applicable, easy to administer in a short amount of time, and based on a scientific approach. The total score ranges from 0 to 100, with higher scores indicating greater autonomic dysfunction.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Pain (P-VAS)
Using a visual analogue scale, patients mark a point on a line representing a continuum from "no pain" to "worst pain," with scores ranging from 0 to 100, where higher scores indicate greater pain.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)]
University of California-Los Angeles (UCLA) Loneliness Scale (3-item)
The UCLA Loneliness (3-item) Scale scores range from 3 to 9, with higher scores indicating greater perceived loneliness.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Adapted Berkman-Syme Social Network/Connection Index
This is a self-report questionnaire used to assess social integration and isolation, focusing on marital status, frequency of contact, and participation in social activities, particularly relevant for older adults. Each item is scored on a scale from 1-4 where higher values reflect greater frequency (e.g., 4 = "5 or more times a week"). For each respondent, a sum score is calculated by adding the scores of all five items, yielding a possible score range of 5-25. Higher sum scores reflect higher levels of social connection and lower social isolation.
Measured: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start18 Apr 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long COVID-19Studies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- PolyBio Research Foundation, The Anlyan Center
- Responsible party
- Principal investigator, David Putrino, Icahn School of Medicine at Mount Sinai
- Investigators
- David Putrino, PT, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06960928
- Sponsor's protocol ID
- STUDY-24-01366
- Status last verified
- Mar 2026
- First submitted
- 29 Apr 2025
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose Sirolimus in People With Post-Acute Sequelae of COVID-19 (PASC) Long COVID-19
- ClinicalTrials.gov ID
- NCT06960928
- Acronym / sponsor ID
- STUDY-24-01366
- Conditions
- Long COVID-19
- Keywords
- Long COVID-19, Post-Acute Sequelae of COVID-19 (PASC), Sirolimus, Rapamycin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- PolyBio Research Foundation, The Anlyan Center
- Study start
- 18 Apr 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 7 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low-dose sirolimus | Experimental | Drug: Low-dose sirolimusParticipants will follow the escalation scheme and receive sirolimus for up to 12 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will follow the escalation scheme and receive the placebo for up to 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
Key exclusion criteria (21 listed)
- Pre-existing conditions including, but not limited to:
- Current use of sirolimus
- Taking a medication with known interactions to sirolimus:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-dose sirolimusAlso: rapamycinParticipants 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 | Low-dose sirolimus |
| PlaceboParticipants 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) | Drug | Placebo |
Primary outcome
European Quality of Life-Visual Analogue Scale (EQ-VAS)
Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
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.
14 secondary outcomes
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)]
University of California-Los Angeles (UCLA) Loneliness Scale (3-item)
Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Adapted Berkman-Syme Social Network/Connection Index
Time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Putrino, PT, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Low-dose sirolimus in people with Long COVID-19, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Putrino, PT, PhD (212-241-7658, coreresearch@mountsinai.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
European Quality of Life-Visual Analogue Scale (EQ-VAS) (time frame: Baseline (Week 0) and Post-treatment (Week 12 and Week 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2026.