Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL)

Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL): A Prospective, Double-Blind, Placebo-Controlled Trial for Rapamycin in Healthy Individuals Assessing Safety and Efficacy in Reducing Aging Effects

This is a randomized, placebo-controlled trial into the safety and efficacy in reducing clinical measures of aging in an older adult population.

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Drug: Placebo; Drug: Rapamycin

Detailed Description

A randomized, double-blind, placebo-controlled trial assessing the effects of low and high doses of intermittent Rapamycin on a weekly schedule. The researchers aim to establish a long-term safety profile, determine the long-term efficacy of Rapamycin in reducing clinical aging measures, and biochemical and physiological endpoints associated with declining health and aging in healthy older adults.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60605
      • AgelessRx

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 50-85
• Any sex
• Any ethnicity
• Interest in taking Rapamycin off-label
• Willing to undergo tests
• Relatively good health with only well-managed chronic diseases (hypertension, coronary artery disease, type II diabetes, etc.) clinically stable
• Adequate cognitive function to be able to give informed consent
• Technologically competent to complete web forms and perform video calls with the PI

Exclusion Criteria:

• Anemia - Hg < 9.0 g/dl, Leukopenia - white blood cells (WBC) < 3,500/mm3 , Neutropenia - absolute neutrophil count < 2,000/mm3 , or Platelet count - platelet count < 125,000/mm3
• Premenopausal females (due to menstruation-induced anemia, etc.)
• Patients scheduled to undergo major surgery in the next 12 months
• Patients undergoing or scheduled to undergo chemotherapy or any other treatment for malignancy
• Patients scheduled for immunosuppressant therapy for transplant
• Patients with impaired wound healing or history of a chronic open wound
• Untreated dyslipidemia with LDL-c > 190 and family history of dyslipidemia, Total cholesterol > 350 mg/dl, or triglycerides > 880 mg/dl.
• Impaired hepatic function, including elevated alkaline Phosphatase levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Albumin, or T. Bili.
• HIV/AIDS, chronic Lyme, Babesia, Ehrlichiosis, Anaplasmosis, or other chronic infections that require ongoing treatment or monitoring
• Allergy to Rapamycin
• Any form of clinically relevant primary or secondary immune dysfunction or deficiency (e.g. X-linked agammaglobulinemia (XLA), common variable immunodeficiency (CVID))
• Chronic oral corticosteroid or immunosuppressive medication use (e.g. Enbrel, Humira, methotrexate).
• Fibromyalgia or Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Breast Implant Illness,
• Congestive heart failure: self-assessed functional status of heart failure New York Heart Association (NYHA) classification III or IV
• Impaired renal function, as defined as glomerular filtration rate (GFR) < 30
• Poorly controlled diabetes, as defined as HbA1c > 7%
• Type I Diabetes, or Insulin-dependent Type II diabetes
• Substance abuse disorder either untreated or if treated within the last 5 years
• PTSD, Bipolar disorder, Schizophrenia, or any other untreated or poorly controlled mental health or mood disorder, or history of hospitalization due to mental health condition

• Those who have taken metformin, rapamycin, or rapalogs in the past 6 months

  • (volunteers who were on metformin for aging can participate, provided they agree to stop taking metformin before and during the trial)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapamycin 5; Rapamycin 5 mg/week	Drug: Rapamycin; Rapamycin in 2 different dosage forms.; Other Names: Sirolimus; Rapamune; Rapacan; Siromus; Raparen; Rapasim; Sirova
Experimental: Rapamycin 10; Rapamycin 10 mg/week	Drug: Rapamycin; Rapamycin in 2 different dosage forms.; Other Names: Sirolimus; Rapamune; Rapacan; Siromus; Raparen; Rapasim; Sirova
Placebo Comparator: Placebo 1; Placebo once per week	Drug: Placebo; Placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in visceral fat as measured by dual-energy x-ray absorptiometry (DXA) scan	Visceral fat changes from baseline as determined by DXA scan.	6 month interim analysis of the data, 12 month safety profile will be established

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bone density	Changes in bone density from baseline as determined by DXA scan	6 month interim analysis of the data, 12 month safety profile will be established
lean body mass	Changes in lean body mass from baseline as determined by DXA scan	6 month interim analysis of the data, 12 month safety profile will be established
adverse events	Number of patients with adverse events using standard AE reporting (FDA regulations 21CFR314.80 and 1CFR213.32(s))	6 month interim analysis of the data, 12 month safety profile will be established
complete blood count (CBC)	changes in CBC from baseline	6 month interim analysis of the data, 12 month safety profile will be established
Change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L）measured at baseline and after 6 and 12 months.	Difference in the change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L) compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change of liver function as measured by serum globulin in g/dL, measured at baseline and after 6 and 12 months.	Difference in the change of liver function as measured by serum globulin in g/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change of liver function as measured by serum bilirubin in mg/dL, measured at baseline and after 6 and 12 months.	Difference in the change of liver function as measured by serum bilirubin in mg/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change of liver function as measured by serum alkaline phosphatase, AST, and ALT in IU/L, measured at baseline and after 6 and 12 months.	Difference in the change of liver function as measured by serum alkaline phosphatase, AST, and ALT in IU/L compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change of renal function as measured by serum albumin in g/dL, measured at baseline and after 6 and 12 months.	Difference in the change of renal function as measured by serum albumin in g/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change of renal function as measured by serum creatinine and uric acid in mg/dL, measured at baseline and after 6 and 12 months.	Difference in the change of renal function as measured by serum creatinine and uric acid in mg/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change in lipids (serum total cholesterol, triglycerides, HDL, and LDL cholesterol in mg/dL) measured at baseline and after 6 and 12 months.	Difference in the change of lipids（serum total cholesterol, triglycerides, HDL and LDL cholesterol in mg/dL) compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change in fasting serum glucose in mg/dL, measured at baseline and after 6 and 12 months.	Difference in the change of fasting serum glucose in mg/dL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change in insulin in uIU/mL, measured at baseline and after 6 and 12 months.	Difference in the change of fasting serum insulin in uIU/mL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change in fasting serum IGF-1 in ng/mL, measured at baseline and after 6 and 12 months.	Difference in the change of fasting serum IGF-1 in ng/mL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established
Change in serum Hemoglobin A1c in % of total hemoglobin, measured at baseline and after 6 and 12 months.	Difference in the change of serum Hemoglobin A1c in % of total hemoglobin compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.	6 month interim analysis of the data, 12 month safety profile will be established

Collaborators and Investigators

• Sponsor: AgelessRx
• Collaborators: University of California, Los Angeles
• Investigators: Study Director: Sajad Zalzala, MD, AgelessRx; Principal Investigator: James Watson, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): December 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 26, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: aging; sirolimus; rapamycin; healthy aging; longevity; age-related conditions
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: ALRx001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: as soon as available
• IPD Sharing Access Criteria: Institutional review board (IRB) approval or at the discretion of PI/sponsor
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No