A Study of Exercise and Pharmacologic Intervention on Systemic Inflammation

Mount Sinai Health System

Status and phase: Enrolling; Phase 1

Conditions: Smokers; Former Smokers

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07058974

STUDY-24-01678

Details and patient eligibility

About

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.

Enrollment: 22 estimated patients

Sex: All

Ages: 65 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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22 participants in 2 patient groups

Exercise and spermidine administered in conjunction with lamivudine (RTi)

Experimental group

Description:

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

Treatment:

Dietary Supplement: Spermidine

Drug: lamivudine

Behavioral: Exercise Regimen

Exercise and spermidine administered in conjunction with rapamycin (mTORi)

Experimental group

Description:

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

Treatment:

Dietary Supplement: Spermidine

Drug: rapamycin

Behavioral: Exercise Regimen