Exercise plus spermidine with either rapamycin or lamivudine to lower systemic inflammation in older smokers
A Phase 1b, Multi-cohort Clinical Trial Assessing Safety and Feasibility of Exercise and Spermidine Administered in Conjunction With Lamivudine (RTi) or Rapamycin (mTORi) to Assess Impact on Dynamic Changes of Inflammation and Aging
This Phase 1 study will test whether an exercise program combined with spermidine and either rapamycin or lamivudine can reduce systemic inflammation in current and former smokers aged 65–80.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 22 (estimated) |
| Ages | 65 Years to 80 Years |
| Sex | All |
| Sponsor | Icahn School of Medicine at Mount Sinai Academic / other |
| Locations | 1 site (New York, New York) |
| Trial ID | NCT07058974 on ClinicalTrials.gov |
What this trial studies
This single-center Phase 1 interventional trial at Mount Sinai combines a structured exercise regimen with daily spermidine supplementation and assignment to either rapamycin or lamivudine to test feasibility, safety, and effects on systemic inflammation in older smokers. Enrollment targets current or former smokers aged 65–80 with BMI 25–32 who do not have active cancer, significant kidney disease, severe heart failure, autoimmune disease requiring disease-modifying agents, or chronic active viral infections. The study will monitor adherence, tolerability, adverse events, and changes in inflammatory and aging-related biomarkers over the intervention period. The primary focus is on safety and feasibility rather than definitive clinical efficacy.
Who should consider this trial
Good fit: Ideal candidates are current or former smokers aged 65–80 with BMI 25–32 who have no active cancer treatment, no CKD stage 3/4 or ESRD, no class 3/4 heart failure, no autoimmune disease requiring disease-modifying agents, and no chronic active viral infections.
Not a fit: Patients with recent or active cancer treatment, advanced kidney or heart failure, autoimmune conditions on immunomodulatory biologics, chronic active viral infections, or other exclusionary comorbidities would not be eligible and are unlikely to benefit from this Phase 1 protocol.
Why it matters
Potential benefit: If successful, the combined intervention could lower chronic inflammation and potentially slow age-related decline in lung and systemic health among older smokers.
How similar studies have performed: Preclinical work and small human studies suggest mTOR inhibitors and spermidine can modulate aging biomarkers, but combining these agents with lamivudine and structured exercise in older smokers is novel and has limited prior clinical data.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
New York, New York
- Mount Sinai Hospital — New York, New York, United States (Recruiting)
Study contacts
- Principal investigator: Thomas Marron, MD, PhD — Icahn School of Medicine at Mount Sinai
- Study coordinator: Thomas Marron, MD, PhD
- Email: thomas.marron@mssm.edu
- Phone: (212) 824-9472
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.