Thymus Regeneration TRIIM-X Trial

Greg Fahy PhD and Robert Brooke in close collaboration with Steve Horvath PhD were the first to demonstrate that it may be possible to reverse biological age in humans. Participants in their original TRIIM trial that began in 2015 reduced their biological age by over two years after one year of treatment. The reduction in biological age was clearly evident in all of Horvath’s epigenetic clocks, including GrimAge, which analyzes DNA methylation alterations and provides the most accurate estimate of biological age in humans.

One of the most interesting longevity clinical trials currently underway is the TRIIM-X trial focused on thymus regeneration. This is an expanded pilot clinical study that will evaluate a personalized combination treatment regimen for thymus regeneration. The study, Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial (TRIIM-X) is sponsored by Intervene Immune and scientists are currently recruiting participants. TRIIM-X is focused on reversing a process called thymic involution in the human body. Thymic involution is a major limiting factor for human longevity and it’s part of the reason that 90% of all flu-related deaths happen in people over the age of 65. Thymus regeneration is considered critical for people who are interested in living significantly longer and healthier lives.

Original TRIIM Trial: 2015-2017

Scientists at Intervene Immune believe that thymic involution is reversible using techniques that are available today. To prove this, they conducted a human clinical trial from 2015-2017 called the TRIIM trial. The objective of the study was to reverse thymic involution in healthy men aged 50-65. On September 8, 2019, they published the results from the TRIIM trial in Aging Cell. They documented a variety of effects that are consistent with reversing thymic involution and they also demonstrated an unprecedented reversal of epigenetic aging. While the tests used are not yet FDA approved and therefore are only used for investigational or research purposes, the results indicate a more than two year increase in predicted human lifespan for the trial volunteers. The results were seen across all established epigenetic clocks as well, including Horvath’s GrimAge clock, which analyzes DNA methylation alterations to provide the most accurate measure of biological age available. The TRIIM trial demonstrated – for the first time – that regression of multiple aspects and biomarkers of aging is possible in humans.

“The fact that our treatment reverses epigenetic aging in people teaches us not only something important about human therapeutics, but also something important about aging itself.”

Greg Fahy, PhD, Co-Founder and Chief Scientific Officer, Intervene Immune

Thymic Involution

The thymus is the master gland of immunity that protects the body from foreign invaders such as bacteria and viruses, and it also attacks tumors. Unlike other organs, the thymus is at its largest in children and produces all of your T cells by the time you reach puberty. Over time the thymus undergoes a programmed process of atrophy called involution. When this process starts during puberty, the thymus begins to shrink and is gradually replaced by fat. This results in a massive collapse of the immune system between the ages of 65 and 75. Impaired immune system competence is strongly associated with a big increase in risk of death in humans, both when it happens at younger ages (as in AIDS patients) and when it happens as a result of aging following thymic involution during puberty.

Intervene’s team believes that immunosenescence is a key driver of human aging. They want to make therapies and diagnostics available to eliminate the collapse of the immune system that occurs with age and is associated with a marked increase in cancer, cardiovascular disease, and overall risk of mortality. Treatments are available combined with diagnostics to carefully monitor treatment and immune system status. Intervene researchers have pioneered approaches to monitor safety as well as efficacy of methods to maintain immune system health and prevent immunosenescence. These methods have also been validated in a clinical trial with collaborators from major research universities including UCLA and Stanford University. Intervene’s program is adaptive, where adjustments are made at frequent intervals based on blood draws, including safety monitoring and also cutting-edge biomarkers of immune status and aging status.

The Current TRIIM-X Trial

The current TRIIM-X trial is an expanded pilot clinical study that will evaluate a personalized combination treatment regimen for thymus regeneration. The study will evaluate biomarkers for epigenetic aging and immunosenescence, as well as evaluate established clinical measures and risk factors for prevention of physical frailty, cancer, cardiovascular disease, diabetes, dementia, and infectious diseases. The objective of the study is to obtain information needed for designing an effective personalized and adaptive treatment regimen for a larger and more diverse study population, and to obtain additional proof of principle for the use of the TRIIM medications and biomarkers for reversing epigenetic aging and immunosenescence as new forms of preventive medicine.

The study uses multiple agents in combination with personalized doses of recombinant human growth hormone (somatropin), metformin, and DHEA, in a similar manner to how the combination treatment was applied in the earlier TRIIM trial at Stanford, which demonstrated strong statistical significance for the primary efficacy endpoints that will be evaluated in TRIIM-X. Somatropin is approved by the FDA for adult growth hormone deficiency and its use in the study is guided by prior safety data established for that use and also based on safety data available on its prior use in the TRIIM trial and in clinical practice in healthy elderly individuals. Control groups to enable testing of biomarker variability and the contributions of individual medications are planned pending additional trial sponsorship.

Primary Outcome Measures

  1. Epigenetic Age (Time Frame: 12 months) DNA methylation based epigenetic age (GrimAge)
  2. Thymus Regeneration (Time Frame: 12 months) Thymic density based on MRI or CT
  3. Safety and Tolerability (Time Frame: 12 months) Incidence of treatment-related adverse effects

Secondary Outcome Measures

  1. Immunosenescence (Time Frame: 12 months) Assessment of naive T cells and immune cell function

    Enrolling in the TRIIM-X Trial

    1. Participants are currently being recruited for TRIIM-X.
    2. You can read about the study Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial (TRIIM-X on
    3. To start you will complete a brief online survey to help determine initial eligibility for treatment. A member of the clinical trial team will then discuss your health status with you and determine your enrollment options. If the team decides that enrollment makes sense, they will discuss the logistics involved and arrange for initial baseline blood draws and assessments.
    4. Men and women age 40-80
    5. The duration of treatment will be 12 months
    6. The cost to participate in the full treatment protocol in the TRIIM-X clinical trial is approximately $18,000. The cost will vary from person to person. The cost to participate as an untreated control volunteer is expected to be less than $1,000 for one year of advanced epigenetic and immunological health monitoring, and may be $0 depending on the level of trial sponsorship obtained.
    7. Intervene Immune is based in the Los Angeles area. Participants who do not live in Los Angeles may participate in the clinical trial remotely using telemedicine
    8. There are logistical challenges with extending TRIIM-X enrollment outside of the US but they are working on this so international access may become available in the future.
    9. For additional details or follow-up information including if you would like to enroll in a clinical trial, receive treatment, or invest in the company, please fill out the form on the company website.
    10. If you have questions please send email to or call (833)3-IMMUNE

This article was written by Margaretta Colangelo

About the author: Author: Margaretta Colangelo

Co-founder and CEO of Jthereum

Margaretta is Co-founder and CEO of Jthereum, an enterprise Blockchain technology company. She has published over 150 articles on DeepTech, AI, Blockchain, and Longevity. In 2020, she summarized over 1,000 research papers on COVID-19. Margaretta serves on the Advisory Boards of the AI Precision Health Institute at the University of Hawai‘i Cancer Center, NaNotics, Robots Go Mental, and on the Board of Directors of the Bring Hope Humanitarian Foundation. She is based in San Francisco.


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