Human Albumin Combined With Plasma Exchange for Frailty Intervention

Frailty is a common age-related clinical syndrome characterized by progressive decline in physiological reserve, reduced stress tolerance, and multisystem functional impairment in older adults. It significantly increases the risk of adverse outcomes including falls, hospitalizations, functional dependence, and all-cause mortality. Chronic low-grade inflammation, immune senescence, oxidative stress, and abnormal protein modification are considered key biological mechanisms driving the onset and progression of frailty. Current mainstream interventions, such as nutritional support and physical exercise, have shown only limited efficacy in moderate to severe frailty, and targeted biological therapies for frailty remain lacking. This study aims to evaluate the efficacy and safety of plasma exchange combined with human albumin (ALB), with or without adjunctive intravenous immunoglobulin (IVIg), in the treatment of frailty, and to preliminarily explore the potential mechanisms underlying the combined therapy.

This is a prospective, randomized, exploratory clinical trial. A total of 34 participants with a FRAIL scale score of ≥ 1 will be enrolled and randomly assigned at a 1:1 ratio into two groups (17 participants in each group): the plasma exchange plus human albumin group (ALB group) and the plasma exchange plus human albumin plus intravenous immunoglobulin group (ALB + IVIg group). The study is divided into three phases: a screening phase, a treatment phase, and a follow-up phase.

The screening phase will be conducted within 7 days prior to the first treatment. Eligible subjects will sign an informed consent form and complete a comprehensive baseline assessment, including frailty status evaluation, physical function testing, routine laboratory and imaging examinations, frailty-related biomarker detection, albumin (ALB) modification profiling, and inflammatory marker testing to confirm eligibility.

The treatment phase will last for 5 months, consisting of a total of 6 treatment sessions administered monthly. Systemic assessments will be performed at each visit, including frailty status evaluation, physical function testing, routine pre-treatment examinations, frailty-related biomarker detection, ALB modification profiling, and inflammatory marker testing, to monitor treatment response and safety. Blood samples for complete blood count and coagulation function will be collected within 1 hour after the first plasma exchange session. All participants will receive plasma exchange with 5% human albumin solution as the replacement fluid, according to the study protocol. Subjects in the ALB + IVIg group will additionally receive intravenous immunoglobulin (IVIg) immediately after each plasma exchange session. Adverse events will be recorded throughout the study.

Follow-up visits will be conducted at 1, 3, and 6 months after the final treatment session. All assessments and laboratory tests will be repeated to evaluate the long-term efficacy, safety, and sustained effects of the interventions.

This trial has not yet been initiated. It is expected that within-group and between-group comparisons will clarify the therapeutic effects and long-term stability of the two regimens, as well as their safety profiles. Changes in frailty-related biomarkers, inflammatory markers, and albumin modification patterns will help to illustrate the potential molecular mechanisms of plasma exchange combined with functional protein supplementation for frailty. It is hypothesized that plasma exchange combined with ALB (with or without IVIg) may exert multi-targeted intervention on frailty by eliminating aging-related toxic factors and restoring plasma and immune homeostasis. The findings of this study will provide preliminary clinical evidence and a theoretical basis for novel biological therapeutic strategies for frailty.

Inclusion criteria

• Age ≥ 18 years.
• Clear consciousness and ability to communicate.
• Sufficient cognitive function and educational level to complete all study-related assessments.
• A score of ≥ 1 on the FRAIL scale.
• Voluntary written informed consent.

Exclusion criteria

• Known allergy or hypersensitivity to albumin (ALB) or intravenous immunoglobulin (IVIg).
• Currently receiving albumin (ALB) and/or intravenous immunoglobulin (IVIg) infusion for other reasons.
• Severe cardiac, hepatic, or renal insufficiency.
• Active infection or acute exacerbation of chronic infection.
• Current use of direct oral anticoagulants (DOACs).
• History of bleeding disorders or coagulation dysfunction.
• Concomitant malignancy or expected survival of less than 6 months.
• Severe visual, auditory, or motor function impairment.
• Refusal to sign the informed consent form.
• Other conditions that, in the opinion of the investigator, make the participant unsuitable for the study.