Indications for an antidepressive effect of thymosin alpha-1 in a small open-label proof of concept study in common variable immune deficiency patients with depression.

Small open-label, proof of concept trial

“We conducted an open-label, proof of concept trial (EudraCT number 2017-005001-12).”

Five depressed CVID patients and a contrast group of 42 MDD patients treated as usual

“Five depressed CVID patients (Hamilton Depression Rating Scale, HDRS >12) could be treated with Tα1 (8 weeks, 1.6 mg daily subcutaneously, 1st week, thereafter 1.6 mg twice weekly). At the start, at 8 weeks and 8 weeks after the last injection, the HDRS was recorded and blood samples drawn for measuring naïve and memory T cells, Th17 and Treg cells, hsCRP, IL-6 and IL-7. Outcomes were compared to those of a contrast group (42 MDD patients, same severity but treated as usual (TAU)).”

5 CVID patients, 42 MDD patients, and 20 healthy controls

“These were also compared to the outcomes in the contrast group of 42 patients with MDD who received treatment as usual (TAU) and to the control group of 20 healthy controls (HC).”

8 weeks of treatment followed by an 8-week wash-out period

“Patients received Thymosin-α1 (Tα1, thymalfasin, Zadaxin, SciClone Pharmaceuticals, Sjanghai, China) 1.6 mg subcutaneously every day (first week) and thereafter twice a week for a consecutive seven weeks (in total eight weeks).”

All five CVID patients showed a decrease in depression severity scores during treatment

“In all 5 depressed CVID patients HDRS decreased during Tα1 treatment (with average 52%, TAU decreased scores with 36% in MDD patients).”

Treatment resulted in an increase in naïve/memory CD4+ and CD8+ T cell ratios in all patients

“All 5 CVID patients showed an increase in naïve/memory CD4+ and CD8+ T cell ratios, and in 4 of the 5 patients with detectable IL-6 levels reductions were recorded.”

Depression recurred in the two most severe patients during the wash-out period, and immune effects were not sustained

“In the 8-week wash-out, depression recurred in the 2 most severe patients, while continued to improve in the others. Immune effects were not sustained in the wash-out.”

Non-placebo-controlled design and very small sample size limiting statistical power

“One of the major limitations of this study is the non-placebo-controlled design of the study, limiting a detailed statistical evaluation.”