Rapamycin for Aging

(mTOR Trial)

Recruiting at 1 trial location

Overseen By Dean Kellogg, Jr., MD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Cytochrome P450 drugs, Immunosuppressants

Disqualifiers: Diabetes, Liver disease, Smoking, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether rapamycin, a drug already used to prevent organ transplant rejection, can improve heart and brain function in older adults. Researchers hope it might boost the immune system and overall health in people aged 70 to 95. Individuals who are generally healthy and have stable chronic conditions, such as high blood pressure, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain drugs that affect rapamycin metabolism or have been on long-term immunosuppressants recently.

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

Research has shown that rapamycin hasn't been linked to any serious side effects in healthy individuals. However, some studies found that those taking the drug may face a higher risk of infections. The FDA has approved rapamycin to prevent organ transplant rejection, indicating its safety for that use. Its full safety profile is still under investigation when used for other purposes, such as slowing aging. Generally, researchers are examining low doses of rapamycin for potential benefits in healthy aging. While its effects on aging are still being studied, current data suggest it is usually well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aging?

Unlike the standard treatments for aging, which often focus on cosmetic improvements or general health maintenance, Rapamycin targets the cellular mechanisms that contribute to aging. Most treatments aim to address the symptoms of aging, but Rapamycin works at the biological level by inhibiting the mTOR pathway, which is involved in cell growth and aging. Researchers are excited about Rapamycin because it has the potential to slow down the aging process itself, rather than just treating its visible effects. This unique mechanism of action opens the door to not just extending lifespan, but also improving overall health during aging.

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

Research has shown that rapamycin, an FDA-approved drug, may aid in aging. Animal studies found that rapamycin can extend lifespan and enhance health by boosting immune function and improving cancer survival rates. In humans, low doses of rapamycin have been suggested to support healthy aging. Evidence indicates that rapamycin and similar drugs might strengthen the immune and heart systems, which often weaken with age. For this reason, researchers are studying rapamycin in this trial for its potential to help older adults maintain better health. ^{1 2 3 5 6}

Who Is on the Research Team?

Dean Kellogg, Jr., MD

Principal Investigator

The University of Texas Health Science Center at San Antonio

Are You a Good Fit for This Trial?

This trial is for healthy elderly individuals aged 70-95 with stable chronic conditions. They must pass an MRI safety screening and have no history of skin ulcers, liver disease, poorly controlled diabetes, or recent use of certain medications like systemic immunosuppressants or drugs affecting cytochrome P450 3A. Smokers and females are excluded to avoid sex-based response differences.

Inclusion Criteria

You need to be in good overall health, which means you should feel physically and mentally well, and have a good social life.

My chronic conditions, like high blood pressure or heart disease, are under control.

For cardiac and brain imaging by MRI, a pre-MRI screening questionnaire will be used to assess MRI safety and neurological health

Exclusion Criteria

I am a female interested in participating in a clinical trial.

I have been on long-term immunosuppressants like prednisone in the past year.

Exclusion criteria for MRI scan: known claustrophobia, metal implants in soft tissue of the body including pacemakers, aneurysm clips, ferrous metal fragments not anchored to bone (bullets, BBs, shrapnel, metal shavings), implanted medication pumps, and oral-facial metal appliances that are permanently secured but may result in low image quality. Participants may also be excluded for history of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rapamycin 1mg for 8 weeks to evaluate cardiac function using cMRI

8 weeks

2 visits (in-person) for MRI assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rapamycin

Trial Overview The study tests if rapamycin can improve life functions in the elderly by focusing on cardiac function. Participants will receive rapamycin treatment as part of Substudy E to see if it benefits heart health similar to effects seen in animal studies.

How Is the Trial Designed?

Group I: Rapamycin Experimental Treatment 1 Intervention

Rapamycin 1mg for 8 weeks

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

Approved in European Union as Rapamune for:

• Prevention of organ transplant rejection
• Lymphangioleiomyomatosis
• Perivascular epithelioid cell tumors

Approved in United States as Rapamune for:

• Prevention of organ transplant rejection
• Lymphangioleiomyomatosis
• Perivascular epithelioid cell tumors

Approved in Canada as Rapamune for:

• Prevention of organ transplant rejection
• Lymphangioleiomyomatosis

Approved in Japan as Rapamune for:

• Prevention of organ transplant rejection

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

The Claude D. Pepper Older Americans Independence Centers

Collaborator

Trials

11

Recruited

350+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Rapamycin, an FDA-approved drug, inhibits the mTOR protein kinase, which is crucial for nutrient signaling, and has shown potential to promote longevity in various organisms, including mice.

The article discusses both the anti-aging effects of rapamycin and strategies to safely inhibit mTOR signaling to minimize side effects, highlighting its promise as an anti-aging compound.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of the Mechanistic Target of Rapamycin (mTOR)-Rapamycin and Beyond. Lamming, DW.[2021]

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]

Rapamycin, an mTORC1 inhibitor, has shown promise in extending lifespan and delaying age-related diseases, but concerns about serious side effects like immunosuppression have limited its use in humans.

Research suggests that the negative side effects of rapamycin may be linked to its inhibition of mTORC2, and ongoing clinical trials are exploring dosing strategies that could selectively target mTORC1 to enhance safety and efficacy in treating age-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blazing a trail for the clinical use of rapamycin as a geroprotecTOR. Konopka, AR., Lamming, DW.[2023]

Rapamycin, an inhibitor of the TOR pathway, is a promising non-toxic drug that may help increase lifespan and combat age-related diseases, making it suitable for daily use.

In addition to its potential anti-aging effects, rapamycin has shown benefits such as anti-tumor properties and bone preservation, suggesting it could have multiple health advantages beyond longevity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-aging drug today: from senescence-promoting genes to anti-aging pill. Blagosklonny, MV.[2018]

Research suggests that aging may be driven by a quasi-program influenced by the TOR pathway rather than by molecular damage, supporting the idea that targeting this pathway could be key to anti-aging therapies.

Sirolimus (rapamycin) has shown promising results in extending lifespan and improving health in various animal models, indicating its potential as a significant anti-aging treatment for humans in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapamycin and quasi-programmed aging: four years later. Blagosklonny, MV.[2020]

Pan-mTOR inhibitors, such as Torin1 and PP242, have been shown to effectively suppress cellular aging processes, outperforming rapamycin in reducing senescence-associated changes and preserving the ability of cells to re-proliferate.

These inhibitors work by targeting both mTORC1 and mTORC2 pathways, leading to significant reductions in cellular hypertrophy and promoting a longer 'chronological life span' at concentrations that are lower than those typically used for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gerosuppression by pan-mTOR inhibitors. Leontieva, OV., Blagosklonny, MV.[2021]

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]

Citations

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

Rapamycin for longevity: the pros, the cons, and future ... Across diverse preclinical systems, rapamycin and its analogs have some promise of delaying aging and preventing age-related diseases. While ...

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

What is the clinical evidence to support off-label rapamycin ... Low dose rapamycin therapy has been proposed as a longevity candidate in healthy aging adults. We present a review of the evidence for low dose ...

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

Targeting ageing with rapamycin and its derivatives in ... Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04488601

Participatory Evaluation (of) Aging (With) Rapamycin (for) ... The researchers aim to establish a long-term safety profile, determine the long-term efficacy of Rapamycin in reducing clinical aging measures, and biochemical ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4401992/

Rapamycin and aging: When, for how long, and how much? The drug rapamycin is the only pharmacological agent thus far shown to reproducibly extend lifespan and delay a subset of age-associated pathologies.

6. aging-us.com aging-us.com/news-room/rapamycin-shows-limited-evidence-for-longevity-benefits-in-healthy-adults

Rapamycin Shows Limited Evidence for Longevity Benefits ... The researchers emphasize that rapamycin's role in human aging is still uncertain. Off-label use is growing among longevity clinics and ...