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

• ClinicalTrials.gov Identifier: NCT04488601
• Recruitment Status: Completed
• First Posted: July 28, 2020
• Last Update Posted: January 24, 2024
• Sponsor: AgelessRx
• Collaborator: University of California, Los Angeles
• Information provided by (Responsible Party): AgelessRx

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Aging	Drug: Rapamycin; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Prospective, Double-Blind, Placebo-Controlled Trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: January 1, 2020
• Actual Primary Completion Date: December 30, 2023
• Actual Study Completion Date: December 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. bone density [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   Changes in bone density from baseline as determined by DXA scan
2. lean body mass [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   Changes in lean body mass from baseline as determined by DXA scan
3. adverse events [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   Number of patients with adverse events using standard AE reporting (FDA regulations 21CFR314.80 and 1CFR213.32(s))
4. complete blood count (CBC) [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   changes in CBC from baseline
5. Change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L）measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   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. Change of liver function as measured by serum globulin in g/dL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   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.
7. Change of liver function as measured by serum bilirubin in mg/dL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   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.
8. 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. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   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.
9. Change of renal function as measured by serum albumin in g/dL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
   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.
10. Change of renal function as measured by serum creatinine and uric acid in mg/dL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
    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.
11. Change in lipids (serum total cholesterol, triglycerides, HDL, and LDL cholesterol in mg/dL) measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
    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.
12. Change in fasting serum glucose in mg/dL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
    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.
13. Change in insulin in uIU/mL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
    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.
14. Change in fasting serum IGF-1 in ng/mL, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
    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.
15. Change in serum Hemoglobin A1c in % of total hemoglobin, measured at baseline and after 6 and 12 months. [ Time Frame: 6 month interim analysis of the data, 12 month safety profile will be established ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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)

Contacts and Locations

Locations

United States, Illinois

AgelessRx

Chicago, Illinois, United States, 60605

Sponsors and Collaborators

AgelessRx

University of California, Los Angeles

Investigators

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

More Information

• Responsible Party: AgelessRx
• ClinicalTrials.gov Identifier: NCT04488601
• Other Study ID Numbers: ALRx001
• First Posted: July 28, 2020
• Last Update Posted: January 24, 2024
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: as soon as available
• Access Criteria: Institutional review board (IRB) approval or at the discretion of PI/sponsor

• 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

Keywords provided by AgelessRx:

rapamycin; aging; longevity; sirolimus; healthy aging; age-related conditions

Additional relevant MeSH terms:

Sirolimus; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs