What side effects are associated with this type of intervention?

mTORC1 inhibitors like Everolimus, which are being studied for their potential to improve physiological and molecular hallmarks of aging, can have several side effects. Common adverse effects include hyperglycemia, increased susceptibility to infections, liver enzyme elevation, and gastrointestinal issues. Other treatments for aging, such as rapamycin, have shown beneficial responses but also unexpected effects on reproduction and other areas that require further investigation. It is important to monitor these side effects closely and discuss them with a healthcare provider.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for aging. However, Everolimus, an mTORC1 inhibitor, is being studied for its potential to improve physiological and molecular hallmarks of aging. This class of drugs, including rapamycin, has shown promise in preclinical studies for extending lifespan and improving healthspan by modulating the mTOR pathway, which is involved in cellular growth and metabolism.

What other types of research exist?

Promising alternatives to Everolimus for aging patients include sirolimus, which has shown efficacy in reducing malignancy rates in transplant patients, and metformin, which has demonstrated benefits in improving disease parameters in polycystic kidney disease models. Additionally, rapamycin and its analogs, such as temsirolimus, are potential alternatives due to their mTOR inhibition properties. These alternatives may offer similar or improved outcomes in managing aging-related conditions.

← Back to Search

mTOR inhibitor

Everolimus for Aging (EVERLAST Trial)

Phase 2

Recruiting

Led By Adam Konopka, PhD

Research Sponsored by University of Wisconsin, Madison

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adults aged 55-80 years old

Ability to take oral medication

Must not have

Taking strong CYP3A4 activators

Alzheimer's

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)

Summary

This trial is testing whether the drug everolimus can safely improve health and slow aging in adults aged 55-80 who are insulin resistant or prediabetic. Everolimus works by blocking a protein involved in cell growth and aging. The study aims to see if this can help improve various aspects of health without serious side effects. Everolimus has been studied for various conditions, including cancer and organ transplantation.

Who is the study for?

This trial is for adults aged 55-80 with insulin resistance or prediabetes, who can take oral medication and are willing to use contraception. Excluded are those with chronic diseases like Alzheimer's, heart disease, kidney disease; tobacco users; on certain drugs affecting everolimus; pregnant/breastfeeding women; and those not proficient in English.

What is being tested?

The study tests if Everolimus (0.5 mg daily or 5 mg weekly) can improve aging signs compared to a placebo over 24 weeks. Participants will be randomly assigned to one of the treatments and monitored up to approximately 38 weeks.

What are the potential side effects?

Everolimus may cause mouth sores or ulcers, increase infection risk due to low white blood cell count, bleeding issues especially when combined with certain medications, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am between 55 and 80 years old.

Select...

I can take pills by mouth.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am currently taking medication that strongly activates CYP3A4.

Select...

I have been diagnosed with Alzheimer's disease.

Select...

I have chronic kidney disease.

Select...

I am taking medication to lower my blood sugar.

Select...

I have bleeding issues or take medication that affects my bleeding time.

Select...

I have a long-term lung condition.

Select...

I am currently taking medication that strongly affects my body's drug processing.

Select...

I have had sores or ulcers in my mouth before.

Select...

I have a brain blood vessel condition.

Select...

I agree not to use St. John's Wort during the trial.

Select...

I have diabetes.

Select...

My cancer is active or I've been in remission for less than 5 years.

Select...

I am allergic to lidocaine or everolimus.

Select...

I have a long-term liver condition.

Select...

I have heart disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention)

This trial's timeline: 3 weeks for screening, Varies for treatment, and 0 (pre-intervention), 4, 8, 12, 16, 20, and 24 weeks (post-intervention) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Metabolic Function: Change in peripheral insulin sensitivity

Secondary study objectives

Cardiac Function: Change in fractional shortening velocity

Cognitive Function: Change in cerebral blood flow

Safety: Change in concentration of blood metabolites/enzymes

+6 more

Other study objectives

Change in concentration of lipid species

Change in skeletal muscle protein abundance

Change in skeletal muscle transcriptome

+13 more

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Daily Placebo and Weekly Everolimus (5mg/week)Experimental Treatment2 Interventions

Once daily placebo and once weekly (5 mg) everolimus taken orally for 24 weeks

Group II: Daily Everolimus (0.5 mg/day) and Weekly PlaceboExperimental Treatment2 Interventions

Once daily (0.5 mg) everolimus and once weekly placebo taken orally for 24 weeks

Group III: Young Adult Reference GroupActive Control1 Intervention

Baseline testing only

Group IV: Daily Placebo and Weekly PlaceboPlacebo Group2 Interventions

Once daily placebo and once weekly placebo taken orally for 24 weeks

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

mTORC1 inhibition, as studied with Everolimus, works by targeting the mechanistic target of rapamycin complex 1 (mTORC1), a critical regulator of cell growth, proliferation, and survival. By inhibiting mTORC1, Everolimus can reduce cellular senescence, enhance autophagy, and improve metabolic functions, which are all processes that deteriorate with age. This matters for aging patients because it can potentially delay the onset of age-related diseases, improve overall healthspan, and enhance the quality of life by maintaining cellular and physiological functions.