Sirolimus for Aging

Overseen By Irina Timofte

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Irina Timofte

Disqualifiers: Chronic liver disease, Cardiovascular diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether sirolimus, a drug that affects cell growth and survival, can slow aging processes. The aim is to reduce the risk of developing chronic conditions, such as certain types of skin cancer. Participants will take a small daily dose of sirolimus and undergo regular health marker checks over a year. The trial seeks participants aged 65-80, postmenopausal women, or those who have undergone surgical sterilization, who can provide informed consent. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings on aging and chronic disease prevention.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial coordinators or your doctor.

Is there any evidence suggesting that sirolimus is likely to be safe for humans?

Research has shown that sirolimus, also known as rapamycin, is usually safe for people. Studies have found that low doses of sirolimus did not cause serious side effects in healthy individuals. However, some individuals experienced more infections than usual. This suggests that while the treatment is mostly safe, there might be a higher risk of infections. Monitoring for any changes or side effects during the treatment is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for aging, which usually focus on symptom management through lifestyle changes and supplements, sirolimus offers a novel approach by targeting the biological mechanisms of aging itself. Sirolimus, an mTOR inhibitor, works by modulating a pathway known to influence cell growth and aging, potentially slowing down the aging process at a cellular level. Researchers are excited about sirolimus because it has the potential to not just alleviate age-related symptoms but to fundamentally alter how aging occurs, opening up possibilities for longer, healthier lifespans.

What evidence suggests that sirolimus might be an effective treatment for aging?

Research has shown that sirolimus, also known as rapamycin, might help slow aging. In many animal studies, sirolimus extended lifespan by up to 20%. It blocks a pathway in the body that affects cell growth and survival, potentially reducing inflammation and improving cell health, both crucial in aging and related diseases. While research in humans continues, early animal studies suggest sirolimus could delay aging and prevent chronic diseases. In this trial, participants will receive either sirolimus or standard care, enabling researchers to evaluate its potential benefits in humans. ^{1 2 3 4 6}

Who Is on the Research Team?

Irina Timofte, M.D.

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals who are 55 years or older. It's designed to explore if Sirolimus, a drug that affects cell growth and survival, can slow down the aging process and prevent age-related diseases.

Inclusion Criteria

I am 55 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 0.5 mg sirolimus orally every day, with weekly monitoring in the first month and monthly follow-ups thereafter

12 months

Weekly visits (first month), monthly visits (thereafter), in-person every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 month

1 follow-up phone call

What Are the Treatments Tested in This Trial?

Interventions

• Sirolimus

Trial Overview The study tests whether Sirolimus can delay signs of aging by affecting cellular pathways linked to inflammation and chronic disease development. Participants will be randomly assigned to receive either Sirolimus or no treatment in a controlled environment.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Patients will be randomized using age-based randomization to initial treatment with 0.5 mg sirolimus p.o. (orally) everyday vs standard of care. The medications would be dispensed from UT Southwestern Medical Center. To ensure patent's safety, all patients will be closely monitored. We will start with a 0.5 mg tablet- the smallest sirolimus dose available. Sirolimus level will be checked weekly in the first month to ensure we maintain a low goal (5-7) that will decrease the risk of developing side effects. In order to monitor study drug compliance, we will ask the patient to keep a pill diary. After the first month, the patient will have monthly blood work and monthly phone call to enquire about potential side effects. The patients will be followed in clinic in person every 3 months. Functional assessment will be obtained at baseline, 3 months 6 months 9 months and 1 year follow up. Completion of the 1-year treatment period will be followed by a follow-up phone call 1 month later.

Group II: Control Active Control 1 Intervention

Interventions: standard of care Patients are not going to receive any additional intervention.

Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in European Union as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Canada as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Japan as Rapamune for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Irina Timofte

Lead Sponsor

Trials

1

Recruited

10+

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

In a phase 1 study involving 32 pediatric patients on dialysis, sirolimus was found to be well tolerated with no serious adverse events reported, indicating its safety for use in this population.

Younger patients (ages 5-11) showed significantly higher clearance rates of sirolimus compared to older patients (ages 12-18), suggesting they may need higher maintenance doses to achieve similar drug levels as healthy adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of ascending single doses of sirolimus (Rapamune, rapamycin) in pediatric patients with stable chronic renal failure undergoing dialysis. Tejani, A., Alexander, S., Ettenger, R., et al.[2022]

Sirolimus (rapamycin) is an effective immunosuppressant approved for preventing graft rejection in kidney transplants, with a lower risk of complications compared to other immunosuppressants.

Recent findings suggest that sirolimus may also have potential in treating skin disorders and extending lifespan, making it a promising candidate for addressing age-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. Peters, T., Traboulsi, D., Tibbles, LA., et al.[2014]

In a study involving 209 kidney transplant recipients in Korea, Rapamune (Sirolimus) demonstrated an acceptable safety profile, with 54.07% of subjects reporting adverse events, most of which were mild and resolved by the end of the study.

The efficacy of Rapamune was notable, with a low incidence of biopsy-proven acute rejection at 2.87% and a high graft survival rate of 99.51%, indicating its effectiveness in preventing kidney allograft rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Rapamune® (Sirolimus) in kidney transplant recipients: results of a prospective post-marketing surveillance study in Korea. Jeon, HJ., Lee, HE., Yang, J.[2019]

Inhibitors of mTOR, like rapamycin and Everolimus, are effective in suppressing cellular aging and can extend lifespan across various species, while also preventing age-related diseases such as cancer and neurodegeneration.

Combining rapamycin with other medications like metformin and statins, along with lifestyle changes such as exercise and a healthy diet, can enhance its anti-aging effects and reduce potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From rapalogs to anti-aging formula. Blagosklonny, MV.[2021]

A survey of 333 adults using rapamycin off-label for healthspan maintenance suggests that the drug can be used safely in individuals with normal health status.

This study provides initial evidence regarding the characteristics of those using rapamycin, addressing the limited data on its side effects and efficacy in a preventative context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of off-label rapamycin use to promote healthspan in 333 adults. Kaeberlein, TL., Green, AS., Haddad, G., et al.[2023]

Sirolimus is a powerful immunosuppressant used in kidney transplantation that works by inhibiting the mTOR pathway, which is crucial for cell growth and proliferation, leading to reduced rates of acute rejection episodes to less than 10% when combined with cyclosporin A (CsA).

In clinical trials, using sirolimus at doses of 2 or 5 mg/day alongside CsA and steroids resulted in acute rejection rates of only 19% and 14% within 12 months, while also potentially reducing the need for nephrotoxic calcineurin inhibitors, although it may cause side effects like myelosuppression and increased lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a comprehensive review. Kahan, BD.[2019]

Rapamycin can effectively extend the lifespan of bone marrow mesenchymal stromal cells (BM-MSCs) derived from healthy donors, although the degree of effectiveness varies among different samples.

The mechanism behind rapamycin's ability to delay senescence is linked to the repression of the p16INK4A protein, rather than changes in other senescence or pluripotency markers like IL6 and NANOG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individual response to mTOR inhibition in delaying replicative senescence of mesenchymal stromal cells. Antonioli, E., Torres, N., Ferretti, M., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226543/

Rapamycin for longevity: the pros, the cons, and future ... Transient, short-term rapamycin treatment in early adulthood improved late-life health outcomes in mice, extending lifespan in both sexes at ...

2. thelancet.com thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext

Targeting ageing with rapamycin and its derivatives in ... Sirolimus drug summary​​ Animal studies have shown that decreased mTOR signalling extends lifespan by up to 20% in yeast, 18.

3. aging-us.com aging-us.com/article/206300/text

What is the clinical evidence to support off-label rapamycin ... Despite the preclinical evidence supporting the use of sirolimus to enhance mean and maximal lifespan, the data in humans have yet to establish ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10415559/

Towards disease-oriented dosing of rapamycin for longevity Rapamycin (Sirolimus) is the only one drug that consistently extends life span in countless animal studies in all species tested [1–19] and see ...

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05237687

Study Details | NCT05237687 | The Role of Sirolimus in ... Our overarching hypothesis is that sirolimus is one of the first pharmacological agents that will impact the aging process and chronic disease development.

6. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/jcph.70112

Risks and Benefits for Sirolimus in Aging Prevention - S. Similarly, many other vivo studies have demonstrated that sirolimus can alleviate age-related dysfunctions, delay tumor onset, decrease the rate ...