A Study of Exercise and Pharmacologic Intervention on Systemic Inflammation

NCT ID: NCT07058974

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-25
• Study Completion Date: 2026-07-01

Brief Summary

This is a study assessing the feasibility of performing an anti-aging intervention which is a combination of an exercise regimen, spermidine supplementation, and either rapamycin or lamivudine.

Conditions

Smokers; Former Smokers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Exercise and spermidine administered in conjunction with lamivudine (RTi)

Participants will perform an exercise regimen and take spermidine and lamivudine for 180 days.

Group Type: EXPERIMENTAL

lamivudine

Intervention Type: DRUG

Lamivudine (Epivir) is a drug used typically to treat HIV and Hepatitis B Virus (HBV). It has not been studied when given in combination with spermidine.

Exercise Regimen

Intervention Type: BEHAVIORAL

All experimental groups will receive an exercise regimen combining high-intensity interval training (HIIT) (targeting aerobic fitness) and resistance training (targeting strength and skeletal muscle mass preservation). The HIIT exercise component will consist of 2 sessions per week totaling 20 minutes per session. The resistance training component will consist of 3 sessions per week totaling 40 minutes per session.

Spermidine

Intervention Type: DIETARY_SUPPLEMENT

Spermidine is a polyamine that forms naturally in plants, animals, and microorganisms as a byproduct of protein breakdown. Participants will take an oral dosage of 2mg/day for 180 days.

Exercise and spermidine administered in conjunction with rapamycin (mTORi)

Participants will perform an exercise regimen and take spermidine and rapamycin for 180 days.

Group Type: EXPERIMENTAL

rapamycin

Intervention Type: DRUG

Rapamycin (Rapamune, Sirolimus) is an FDA-approved drug and indicated for use as an immune modulator.

Exercise Regimen

Intervention Type: BEHAVIORAL

All experimental groups will receive an exercise regimen combining high-intensity interval training (HIIT) (targeting aerobic fitness) and resistance training (targeting strength and skeletal muscle mass preservation). The HIIT exercise component will consist of 2 sessions per week totaling 20 minutes per session. The resistance training component will consist of 3 sessions per week totaling 40 minutes per session.

Spermidine

Intervention Type: DIETARY_SUPPLEMENT

Spermidine is a polyamine that forms naturally in plants, animals, and microorganisms as a byproduct of protein breakdown. Participants will take an oral dosage of 2mg/day for 180 days.

Interventions

lamivudine

Lamivudine (Epivir) is a drug used typically to treat HIV and Hepatitis B Virus (HBV). It has not been studied when given in combination with spermidine.

Intervention Type: DRUG

rapamycin

Rapamycin (Rapamune, Sirolimus) is an FDA-approved drug and indicated for use as an immune modulator.

Intervention Type: DRUG

Exercise Regimen

All experimental groups will receive an exercise regimen combining high-intensity interval training (HIIT) (targeting aerobic fitness) and resistance training (targeting strength and skeletal muscle mass preservation). The HIIT exercise component will consist of 2 sessions per week totaling 20 minutes per session. The resistance training component will consist of 3 sessions per week totaling 40 minutes per session.

Intervention Type: BEHAVIORAL

Spermidine

Spermidine is a polyamine that forms naturally in plants, animals, and microorganisms as a byproduct of protein breakdown. Participants will take an oral dosage of 2mg/day for 180 days.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Epivir; Rapamune, Sirolimus

Eligibility Criteria

Inclusion Criteria

• Patients 65-80 years old
• Current or former smokers
• BMI 25-32
• No cancer requiring active therapy within the last 2 years
• No autoimmune disease requiring disease modifying agents
• No patients with CKD stage 3/4 or ESRD
• No class 3 or 4 heart failure

Exclusion Criteria

• Patients may not have cancer requiring active therapy within the last 2 years
• Patients may not have autoimmune disease requiring disease modifying agents
• Patients may not be receiving immune modifying biologic therapies
• Patients may not have chronic kidney disease stage 3/4 or end stage renal disease
• Patients may not have a known history of metabolic dysfunction-associated steatohepatitis
• Patients may not have a known chronic viral infection such as HIV or active Hepatitis B or C, or a known history of genital HSV. Patients who have spontaneously or through treatment cleared hepatitis B or C are candidates for the trial. If Hepatitis B core ab is positive must document a negative PCR.
• Patients may not have class 3 or 4 heart failure, or have experienced a myocardial infarction or cerebrovascular event in the past 6 months
• Patients may not have uncontrolled diabetes mellitus
• Patients may not have a history of clinically significant interstitial lung disease (ILD).
• Patients may not have clinically significant active wound healing due to recent injury or surgery
• Patients may not have signs or symptoms of clinically significant acute infectious illness on screening laboratory testing or physical examination.
• Patients may not have evidence of active or latent tuberculosis
• Patients may not have nephrotic range proteinuria on screening labs
• Patients may not have received a live virus within one month of study initiation.
• Patients cannot have uncontrolled hypertension (persistent systolic >160; diastolic >100)
• Patients with an inherited primary immunodeficiency
• Patients may not have a history of, or current evidence of, clinically significant chronic liver disease
• Patients may not be receiving any chronic immunosuppressive therapy.
• Patients may not be receiving medications that could increase rapamycin blood concentrations, such as strong inhibitors and inducers of CYP3A4 and/or P-gp (ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin; rifampin or rifabutin), bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, protease inhibitors, metoclopramide, nicardipine, troleandomycin, verapamil. Furthermore, these medications may not be used during the study if patient is assigned to the rapamycin cohort.
• Patients may not be receiving medications that could decrease rapamycin blood concentrations, such as: carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort. Furthermore, these medications may not be used during the study if patient is assigned to the rapamycin cohort.
• Patients may not be receiving medications known to cause angioedema with concomitant use of rapamycin, such as angiotensin-converting enzyme (ACE) inhibitors. Furthermore, these medications may not be used during the study if patient is assigned to the rapamycin cohort.

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Thomas Marron

Director, Early Phase Trials Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Marron, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai Hospital

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Thomas Marron, MD, PhD

Role: CONTACT

thomas.marron@mssm.edu

(212) 824-9472

Facility Contacts

Thomas Marron, MD, PhD

Role: primary

thomas.marron@mssm.edu

(212) 824-9472

Other Identifiers

STUDY-24-01678

Identifier Type: -

Identifier Source: org_study_id