Double-Blind, Placebo-Controlled, Randomized Clinical Trial Demonstrates Telomerase Activator TA-65 Decreases Immunosenescent CD8+CD28- T Cells in Humans

Abstract

TA-65 is a small molecule telomerase activator extracted from Astragalus species. A previous observational study suggested that TA-65 decreased the number of immunosenescent cells in healthy subjects. Here we examined the impact of TA-65 in a much larger randomized, double-blind, and placebo-controlled study. This study aims to evaluate the effects of TA-65 on senescent CD8+CD28- T cells in healthy subjects. This was a randomized, double-blind, placebo-controlled, and multi-arm parallel trial in 500 healthy subjects. Subjects, clinical staff, and primary outcome assessors were blinded until the database lock. A total of 500 healthy volunteers were randomly allocated, 100 subjects each, into one of the five groups; placebo, TA-65 (100 Units) qd, TA-65 (250 Units) qd, TA-65 (500 Units) qd, or TA-65 (250 Units) b.i.d. Change in the immunosenescence biomarker after nine months was measured. The intention-to-treat analysis of the primary outcome measure included all the randomized subjects (n = 500). Per-protocol analysis of the primary outcome measured included 93% of the randomized subjects (n = 424). Multilevel analysis revealed a significant decrease in the CD8+CD28- T cells with TA-65 intervention compared to the placebo group (p<0.05). Intervention by 100 units and 250 units of TA-65 qd led to a decrement of CD8+CD28- T cells by 28 cells/μl, while the intervention by 500 units of TA-65 led to a decrement of CD8+CD28- T cells by 22 cells/μl; the placebo intake led to an increment of CD8+CD28- T cells by 4.38 cells/μl. None of the serious adverse events (9) were deemed related or were unlikely to be related to the product. Adverse events (AEs), ranging from mild to moderate severity were, observed in 34.6% of the subjects. Oral intake of TA-65 significantly decreased CD8+CD28- T cells.