Low Dose Rapamycin in ME/CFS, Long-COVID, and Other Infection Associated Chronic Conditions (ME/CFS)

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 Overview

• Status: Enrolling by invitation
• Conditions: Myalgic Encephalomyelitis; Long-COVID
• Intervention / Treatment: Drug: Rapamycin

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94040
      • Center For Complex Diseases
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • The Mayo Clinic
  • Nevada
    • Incline Village, Nevada, United States, 89451
      • Sierra Internal Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Bateman Horne Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Center For Complex Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients are recruited by study clinicians who are Principal Investigators in this trial.

Description

Inclusion Criteria:

• Diagnosis of ME/CFS that meets the Institute of Medicine (IOM) criteria
• Diagnosis of Long-COVID (PASC clinical criteria)

Exclusion Criteria:

• No diagnosis of ME/CFS or Long-COVID

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Drug: Rapamycin; Once weekly oral rapamycin; Other Names: Sirolimus; Rapamune
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.	Drug: Rapamycin; Once weekly oral rapamycin; Other Names: Sirolimus; Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mTOR activation panel and blood markers involved in autophagy function.	Change in concentrations of phosphorylated autophagy-related gene proteins in blood	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.	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.	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.	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.	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.	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.	1 year

Collaborators and Investigators

• Sponsor: Simmaron Research Inc.
• Collaborators: Mayo Clinic; 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
• Investigators: Principal Investigator: Gunnar Gottschalk, PhD, Simmaron Research Inc.

Publications and helpful links

General 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.
• Gottschalk 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.
• Ruan 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.

Helpful Links

• Simmaron Website

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Actual): February 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Long-COVID; ME/CFS; Infection Associated Chronic Conditions
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Post-Infectious Disorders; COVID-19; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Pathologic Processes; Encephalomyelitis; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic; Organic Chemicals; Macrolides; Lactones; Sirolimus
• Other Study ID Numbers: SRI-RP-2023-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be available to share with non-profit and academic institutions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No