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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune responsiveness, cancer survival, and cognition in laboratory animals. Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95). Substudy E will evaluate the Rapamycin and Cardiac Function.

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.

What evidence supports the effectiveness of the drug rapamycin for aging?

Research shows that rapamycin, a drug that inhibits a protein called mTOR, has been effective in extending lifespan and delaying age-related diseases in animals. It is considered a promising anti-aging drug because it can improve immunity and stem cell function, and it has been shown to prolong life in mice and flies. ^{1 2 3 4 5}

Is Rapamycin safe for human use?

Rapamycin, also known as Sirolimus, is generally considered safe for human use, especially as an immunosuppressant in kidney transplant patients. It has a lower risk of causing kidney, nerve, and certain blood-related complications compared to other similar drugs. However, like any medication, it can have side effects, and its safety profile may vary depending on the specific condition being treated. ^{1 2 5 6 7}

How is the drug Rapamycin unique for aging?

Rapamycin is unique for aging because it inhibits the mTOR protein kinase, which is a key regulator of cell growth and metabolism, and has been shown to extend lifespan in various species. Unlike other treatments, it acts as an anti-aging compound by mimicking calorie restriction and has potential anti-tumor and bone-sparing effects. ^{1 2 5 6 8}

Research Team

Dean Kellogg, Jr., MD

Principal Investigator

The University of Texas Health Science Center at San Antonio

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. [2014]

2. Denmark 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Blazing a trail for the clinical use of rapamycin as a geroprotecTOR. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

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

7. England 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Gerosuppression by pan-mTOR inhibitors. [2021]