NCT Number: NCT06489015
Official Title: Phase 1 Open-label, Exploratory Study of Recombinant Human Serum Albumin (rHSA) for Mild to Moderate Alzheimer's Disease
Study Type: Interventional (Phase 1)
Status: Recruiting
Study Start Date: June 2024
Estimated Enrollment: 30 participants
¶ Background and Rationale
Human serum albumin is the most abundant plasma protein in the human body and plays multiple protective roles in systemic and brain health. Albumin binds and transports a wide variety of molecules, including:
- Fatty acids: Essential for neuronal energy metabolism
- Bilirubin: Potent endogenous antioxidant
- Drugs and hormones: Carrier for therapeutic compounds
- Metals: Binds copper, zinc, and other transition metals
In Alzheimer's disease, several lines of evidence suggest albumin may be beneficial:
- Oxidative stress reduction: Albumin's bilirubin-binding capacity provides antioxidant protection against lipid peroxidation
- Metal ion chelation: Albumin binds redox-active metals (copper, iron) that catalyze Aβ aggregation and oxidative damage
- Aβ binding: Human serum albumin can bind amyloid-beta, potentially reducing its aggregation and toxicity
- Blood-brain barrier transport: Albumin-mediated transport may facilitate drug delivery to the CNS
- Inflammation modulation: Albumin has anti-inflammatory properties through multiple mechanisms
The concept of using albumin as a therapeutic agent for AD is supported by:
- Observational studies showing lower serum albumin levels correlate with cognitive decline in AD
- Albumin replacement studies in other conditions showing neurological benefits
- Preclinical evidence of albumin-mediated neuroprotection
To evaluate the safety and tolerability of recombinant human serum albumin (rHSA) in patients with mild to moderate Alzheimer's disease.
- To assess the pharmacokinetics of rHSA in AD patients
- To explore preliminary efficacy through cognitive assessments
- To measure changes in AD biomarkers (CSF Aβ, tau, NfL)
- To evaluate patient-reported outcomes and quality of life
- Design: Single-arm, open-label, Phase 1 study
- Participants: 30 patients with mild to moderate AD (MMSE 12-26)
- Duration: 12-week treatment period with 4-week follow-up
- Age 50-85 years
- Diagnosis of probable AD (NIA-AA criteria)
- MMSE score 12-26 (mild to moderate dementia)
- Stable on AD medications (cholinesterase inhibitors, memantine) for ≥3 months
- Normal or stable medical conditions
- Other causes of dementia (vascular, Lewy body, frontotemporal)
- Active inflammatory or infectious disease
- Chronic liver disease (albumin synthesis impairment)
- Chronic kidney disease (albumin loss)
- Planned surgeries during study period
| Parameter |
Details |
| Drug |
Recombinant Human Serum Albumin (rHSA) |
| Dose |
1.5 g/kg (approximately 100g for average adult) |
| Route |
Intravenous infusion |
| Frequency |
Weekly infusions |
| Duration |
12 weeks (12 infusions total) |
Safety (Primary):
- Adverse event monitoring
- Vital signs
- Laboratory parameters (CBC, CMP, coagulation)
- Physical and neurological examinations
Efficacy (Secondary):
- Cognitive: ADAS-Cog13, MMSE, MoCA
- Functional: ADCS-ADL, CDR
- Behavioral: NPI, Neuropsychiatric Inventory
- Quality of Life: EQ-5D-5L
Biomarkers:
- CSF Aβ40, Aβ42, total tau, phosphorylated tau
- Plasma NfL, GFAP
- Serum albumin levels and albumin/globulin ratio
Human serum albumin has been shown to:
- Bind Aβ monomers with moderate affinity
- Prevent Aβ fibril formation in vitro
- Reduce Aβ-induced neurotoxicity in cell culture
- Facilitate Aβ clearance through multiple mechanisms
Albumin's capacity to bind bilirubin makes it an important endogenous antioxidant:
- Bilirubin-albumin complexes neutralize reactive oxygen species
- Prevents lipid peroxidation in neuronal membranes
- May reduce 4-HNE and MDA levels in AD brain
Albumin's metal-binding properties may reduce redox-active metal catalysis of Aβ aggregation:
- Binds Cu²⁺ and Fe³⁺ with micromolar affinity
- Prevents metal-induced Aβ aggregation
- May reduce Fenton chemistry and oxidative damage
This trial connects to established mechanisms:
- Safety profile: Characterize tolerability of weekly rHSA infusions in AD patients
- Biomarker trends: Identify changes in CSF and plasma AD biomarkers
- Proof-of-concept: Establish preliminary efficacy signal to guide Phase 2 studies
- Dosing optimization: Determine optimal dose and administration schedule
If successful, rHSA therapy could provide:
- Novel mechanism: First-in-class approach targeting multiple pathways (Aβ, oxidative stress, metal dyshomeostasis)
- Accessibility: Well-characterized protein with established safety profile
- Combination potential: Could be combined with existing AD therapies
- Disease modification: Potential to address underlying pathophysiology