A Study of Exercise and Pharmacologic Intervention on Systemic Inflammation

NCT07058974 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY-24-01678
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Number and Type of Grade 3/4 Adverse Events per CTCAE Version 5.0

  Number and Type of Grade 3/4 Adverse Events per CTCAE Version 5.0. Toxicity will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. Any patient experiencing a Grade 3 or 4 adverse event must hold drug until toxicity returns to grade 0-1. The treating investigator may hold study drug for any duration if the patient is deemed to be experiencing a Grade 1-2 adverse event related to study drug.

  at 180 days

• Number of participants with ability to complete >80% of specified pharmacological intervention

  Feasibility of the trial is determined by participant documentation of taking at least 80% of the provided study drug on a regular basis, ability to complete \>80% of specified pharmacological intervention.

  at 180 days

Secondary Outcomes (1)

• Neutrophil to lymphocyte ratio (NLR)

  at 180 days

Study Arms (2)

Exercise and spermidine administered in conjunction with lamivudine (RTi)

EXPERIMENTAL

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

Drug: lamivudine; Behavioral: Exercise Regimen; Dietary Supplement: Spermidine

Exercise and spermidine administered in conjunction with rapamycin (mTORi)

EXPERIMENTAL

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

Drug: rapamycin; Behavioral: Exercise Regimen; Dietary Supplement: Spermidine

Interventions

lamivudine 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.

Also known as: Epivir

Exercise and spermidine administered in conjunction with lamivudine (RTi)

rapamycin DRUG

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

Also known as: Rapamune, Sirolimus

Exercise and spermidine administered in conjunction with rapamycin (mTORi)

Exercise Regimen 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.

Exercise and spermidine administered in conjunction with lamivudine (RTi); Exercise and spermidine administered in conjunction with rapamycin (mTORi)

Spermidine 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 lamivudine (RTi); Exercise and spermidine administered in conjunction with rapamycin (mTORi)

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Smoking Cessation

Interventions

Lamivudine; Sirolimus; Spermidine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Macrolides; Lactones; Organic Chemicals; Putrescine; Biogenic Polyamines; Biogenic Amines; Amines; Polyamines

Study Officials

• Thomas Marron, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Marron, MD, PhD

CONTACT

(212) 824-9472; thomas.marron@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Early Phase Trials Unit

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: July 10, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Proposals should be directed to thomas.marron@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be determined).

Locations

US (1)