Myalgic EncephalomyelitisNCT06257420
Low Dose Rapamycin in ME/CFS, Long-COVID, and Other Infection Associated Chronic Conditions
An observational study of Myalgic Encephalomyelitis and Long-COVID, run by Simmaron Research Inc. at 5 sites in United States.
Trial summary
The goal of this observational study is to assess the clinical response and the effect of autophagy function in patients before, during and throughout oral low dose sirolimus (rapamycin) therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Myalgic Encephalomyelitis, Long-COVID
- What is being tested?
- Rapamycin
- Type of treatment
- Pill or oral medicine
- How many people
- 150 participants
- Where
- 5 sitesUnited States
- Study dates
- 11 Dec 2023to 1 Jul 2027
- Phase
- Observational
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients are recruited by study clinicians who are Principal Investigators in this trial.
Who may be able to join
- Diagnosis of ME/CFS that meets the Institute of Medicine (IOM) criteria
- Diagnosis of Long-COVID (PASC clinical criteria)
Who cannot join
- No diagnosis of ME/CFS or Long-COVID
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites
Sierra Internal Medicine
Incline Village, Nevada, 89451
Center For Complex Diseases
Palo Alto, California, 94040
The Mayo Clinic
Rochester, Minnesota, 55905
Bateman Horne Center
Salt Lake City, Utah, 84102
Center For Complex Diseases
Seattle, Washington, 98109
About this study
The goal of this observational study is to assess the clinical response and the effect of autophagy function in patients before, during and throughout oral low dose sirolimus (rapamycin) therapy. The main questions this study aims to answer are:
- Does rapamycin reduce the overall symptom burden in this patient population and does it improve the quality of life?
- Does rapamycin change mTOR driven autophagy deficits observed in a subset of patients?
Participants will be asked to complete a series of questionnaires and quality of life instruments before starting rapamycin therapy prescribed by their physician and throughout their course of treatment. Study blood samples will be collected before starting therapy and throughout the course of treatment to assess serological markers of autophagy function.
- Conditions
- Myalgic Encephalomyelitis, Long-COVID
- Being tested
- Rapamycin
- Keywords
- ME/CFS, Long-COVID, Infection Associated Chronic Conditions
- Medical subject headings
- Fatigue Syndrome, Chronic, Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Sirolimus, Rapamune
Once weekly oral rapamycin
| Study group | Role | What they receive |
|---|---|---|
| ME/CFS and Long-COVID patients with serological evidence of autophagy disruption | ME/CFS and Long-COVID patients with serological evidence of autophagy disruption at baseline will be prescribed once weekly rapamycin at a max dose of 6mg per week. Receives: Drug: Rapamycin | |
| ME/CFS and Long-COVID patients without serological evidence of autophagy disruption | ME/CFS and Long-COVID patients without serological evidence of autophagy disruption at baseline will be prescribed once weekly rapamycin at a max dose of 6mg per week. Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Short Form (36) Health Survey
The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Measured: 1 year
Multidemensional Fatigue Inventory (MFI)
The MFI is a 20-item scale designed to evaluate five dimensions of fatigue: general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue.
Measured: 1 year
The Bell Activity Scale
The Bell CFIDS Disability Scale is described in the book, The Doctor's Guide to Chronic Fatigue Syndrome: Understanding, Treating and Living with CFIDS (Bell 1995). This scale assesses functional ability in adult ME/CFS patients. Eleven statements describe patient status such as level of symptoms at rest, level of symptoms with exercise, activity level, and ability to perform work, travel and self care.
Measured: 1 year
Secondary outcomes (7)
Change in mTOR activation panel and blood markers involved in autophagy function.
Change in concentrations of phosphorylated autophagy-related gene proteins in blood
Measured: 1.5 year
DePaul Symptom Questionnaire Short Form- PEM
The DePaul Symptom Questionnaire (DSQ) Post-Exertional Malaise (PEM) items are scored based on both frequency and severity ratings for each symptom Frequency is rated on a 5-point scale from 0 (none of the time) to 4 (all of the time), and severity is rated on a 5-point scale from 0 (symptom not present) to 4 (very severe). These ratings are combined to produce composite scores for each symptom or across items. Higher scores indicate greater symptom burden.
Measured: 1 year
DePaul Symptom Questionnaire- COVID
The DePaul Symptom Questionnaire- COVID (DSQ-COVID) assesses symptoms using frequency and severity ratings for each item. Frequency is scored on a 5-point scale from 0 (none of the time) to 4 (all of the time, and severity is scored on a 5-point scale from 0 (symptom not present) to 4 (very severe). Higher scores indicate greater symptom burden.
Measured: 1 year
FACIT-F (Functional Assessment of Chronic Illness Treatment- Fatigue; Version 4)
The FACIT-F is a self-reported measure of fatigue and its impact on daily activities and functioning. It consists of 13 items, each scored on a 5-point scale from 0 (not at all) to 4 (very much). Item scores are summed to produce a total score ranging from 0 to 52. Higher scores indicate less fatigue and higher quality of life.
Measured: 1 year
Specific Symptom Severity V2.2
The Specific Symptom Severity questionnaire assesses the severity of individual symptoms using a number rating scale. Each symptom is scored from 0 (none) to 10 (very severe). Scores can be reported for individual symptoms or combined across items to produce a total score. Higher scores indicate greater symptom severity.
Measured: 1 year
FUNCAP55 (Functional Capacity) Questionnaire
The FUNCAP-55 is a self-reported measure of functional ability across a range of daily activities. It consists of 55 items. each rated on a scale reflecting the level of difficulty and limitation experienced. Item scores are summed to produce a total score, with higher scores indicating less functional impairment.
Measured: 1 year
Sleep Questionnaire
The Sleep Questionnaire assesses sleep patterns and disturbances using a combination of categorical and numerical responses. Several items are rated on a 5-point frequency scale from 0 (never) to 4 (always, 15-30 times a month), while other items require participants to report specific times or durations (e.g., hours of sleep, time to bed). Higher scores on frequency-based items indicate greater sleep difficulty.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2024
- Study start11 Dec 2023
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Myalgic EncephalomyelitisStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Simmaron Research Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Center For Complex Diseases-Seattle, WA, Sierra Internal Medicine, Incline Village, NV, Center for Complex Diseases- Palo Alto, CA, Simmaron Research Inc. R&D Lab, University of Wisconsin, Milwaukee (UWM), Bateman Horne Center, Salt Lake City, UT, Mayo Clinic
- Responsible party
- Sponsor
- Investigators
- Gunnar Gottschalk, PhD, Principal investigator, Simmaron Research Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06257420
- Sponsor's protocol ID
- SRI-RP-2023-1
- Status last verified
- Apr 2026
- First submitted
- 17 Jan 2024
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will be available to share with non-profit and academic institutions.
Publications
Gottschalk G, Peterson D, Knox K, Maynard M, Whelan RJ, Roy A. Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE). Mol Cell Neurosci. 2022 May;120:103731. doi: 10.1016/j.mcn.2022.103731. Epub 2022 Apr 26.
PubMed 35487443Gottschalk CG, Whelan R, Peterson D, Roy A. Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study. Int J Mol Sci. 2023 May 13;24(10):8713. doi: 10.3390/ijms24108713.
PubMed 37240059Ruan BT, Bulbule S, Gile B, Reyes A, Chheda B, Bateman L, Bell J, Yellman B, Grach SL, Berner J, Peterson DL, Kaufman D, Roy A, Gottschalk CG. Low-dose rapamycin alleviates clinical symptoms of fatigue and PEM in ME/CFS patients via improvement of autophagy: a pilot study. J Transl Med. 2025 Oct 21;23(1):1148. doi: 10.1186/s12967-025-07213-8.
PubMed 41121328Gile B, Bulbule S, Toriola MA, Ruan BT, Marium S, Benko A, Grach S, Mueller M, Bateman L, Bell J, Yellman B, Berner J, Chheda B, Kaufman D, Gottschalk G, Roy A. Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study. J Transl Med. 2026 Jul 10;24(1):921. doi: 10.1186/s12967-026-08575-3.
PubMed 42432754
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 Rapamycin in ME/CFS, Long-COVID, and Other Infection Associated Chronic Conditions
- ClinicalTrials.gov ID
- NCT06257420
- Acronym / sponsor ID
- SRI-RP-2023-1
- Conditions
- Myalgic Encephalomyelitis, Long-COVID
- Keywords
- ME/CFS, Long-COVID, Infection Associated Chronic Conditions
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Simmaron Research Inc.University, hospital or other
- Collaborators
- Center For Complex Diseases-Seattle, WA, Sierra Internal Medicine, Incline Village, NV, Center for Complex Diseases- Palo Alto, CA, Simmaron Research Inc. R&D Lab, University of Wisconsin, Milwaukee (UWM), Bateman Horne Center, Salt Lake City, UT, Mayo Clinic
- Study start
- 11 Dec 2023 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 14 Feb 2024 (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 goal of this observational study is to assess the clinical response and the effect of autophagy function in patients before, during and throughout oral low dose sirolimus (rapamycin) therapy. The main questions this study aims to answer are:
- Does rapamycin reduce the overall symptom burden in this patient population and does it improve the quality of life?
- Does rapamycin change mTOR driven autophagy deficits observed in a subset of patients?
Participants will be asked to complete a series of questionnaires and quality of life instruments before starting rapamycin therapy prescribed by their physician and throughout their course of treatment. Study blood samples will be collected before starting therapy and throughout the course of treatment to assess serological markers of autophagy function.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ME/CFS and Long-COVID patients with serological evidence of autophagy disruption | – | Drug: RapamycinME/CFS and Long-COVID patients with serological evidence of autophagy disruption at baseline will be prescribed once weekly rapamycin at a max dose of 6mg per week. |
| ME/CFS and Long-COVID patients without serological evidence of autophagy disruption | – | Drug: RapamycinME/CFS and Long-COVID patients without serological evidence of autophagy disruption at baseline will be prescribed once weekly rapamycin at a max dose of 6mg per week. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients are recruited by study clinicians who are Principal Investigators in this trial.
Key inclusion criteria (2 listed)
- Diagnosis of ME/CFS that meets the Institute of Medicine (IOM) criteria
- Diagnosis of Long-COVID (PASC clinical criteria)
Key exclusion criteria (1 listed)
- No diagnosis of ME/CFS or Long-COVID
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 |
|---|---|---|
| RapamycinAlso: Sirolimus, RapamuneOnce weekly oral rapamycin | Drug | ME/CFS and Long-COVID patients with serological evidence of autophagy disruption, ME/CFS and Long-COVID patients without serological evidence of autophagy disruption |
Primary outcome
The Short Form (36) Health Survey
Time frame: 1 year
The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.
Multidemensional Fatigue Inventory (MFI)
Time frame: 1 year
The MFI is a 20-item scale designed to evaluate five dimensions of fatigue: general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue.
The Bell Activity Scale
Time frame: 1 year
The Bell CFIDS Disability Scale is described in the book, The Doctor's Guide to Chronic Fatigue Syndrome: Understanding, Treating and Living with CFIDS (Bell 1995). This scale assesses functional ability in adult ME/CFS patients. Eleven statements describe patient status such as level of symptoms at rest, level of symptoms with exercise, activity level, and ability to perform work, travel and self care.
7 secondary outcomes
Change in mTOR activation panel and blood markers involved in autophagy function.
Time frame: 1.5 year
DePaul Symptom Questionnaire Short Form- PEM
Time frame: 1 year
DePaul Symptom Questionnaire- COVID
Time frame: 1 year
FACIT-F (Functional Assessment of Chronic Illness Treatment- Fatigue; Version 4)
Time frame: 1 year
Specific Symptom Severity V2.2
Time frame: 1 year
FUNCAP55 (Functional Capacity) Questionnaire
Time frame: 1 year
Sleep Questionnaire
Time frame: 1 year
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.
- Background: PubMed 35487443Gottschalk G, Peterson D, Knox K, Maynard M, Whelan RJ, Roy A. Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE). Mol Cell Neurosci. 2022 May;120:103731. doi: 10.1016/j.mcn.2022.103731. Epub 2022 Apr 26.
- Background: PubMed 37240059Gottschalk CG, Whelan R, Peterson D, Roy A. Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study. Int J Mol Sci. 2023 May 13;24(10):8713. doi: 10.3390/ijms24108713.
- Results publication: PubMed 41121328Ruan BT, Bulbule S, Gile B, Reyes A, Chheda B, Bateman L, Bell J, Yellman B, Grach SL, Berner J, Peterson DL, Kaufman D, Roy A, Gottschalk CG. Low-dose rapamycin alleviates clinical symptoms of fatigue and PEM in ME/CFS patients via improvement of autophagy: a pilot study. J Transl Med. 2025 Oct 21;23(1):1148. doi: 10.1186/s12967-025-07213-8.
- Derived from this study: PubMed 42432754Gile B, Bulbule S, Toriola MA, Ruan BT, Marium S, Benko A, Grach S, Mueller M, Bateman L, Bell J, Yellman B, Berner J, Chheda B, Kaufman D, Gottschalk G, Roy A. Association of rapamycin treatment with the modulation of purine metabolism, reduced microglial inflammatory responses, improved mitochondrial energy metabolism, and alleviation of fatigue symptoms in ME/CFS subjects: pilot findings from phase-II observational study. J Transl Med. 2026 Jul 10;24(1):921. doi: 10.1186/s12967-026-08575-3.
- Simmaron WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No. IPD will be available to share with non-profit and academic institutions.
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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.
Gunnar Gottschalk, PhD principal investigator
Simmaron Research Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myalgic Encephalomyelitis and Long-COVID, run by Simmaron Research Inc. at 5 sites 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 2 inclusion and 1 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: enrolling by invitation, 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 5 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Short Form (36) Health Survey (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06257420, which also lists 4 linked publications.
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.