| Attribute | Details | |-----------|---------| | Phase | Phase 2 | | Status | Recruiting | | Sponsor | The Methodist Hospital Research Institute | | Intervention | Low-dose IL-2 (interleukin-2) immunotherapy | | Indication | Alzheimer's Disease | | Study Design | Randomized, quadruple-blind, parallel assignment | | Enrollment | 40 participants | | Location | Houston Methodist Research Institute, Houston, Texas |
Study Title
Central and Peripheral Immune Cross-talk in Alzheimer's Disease and Their Modulation by a Novel Immunotherapy
Mechanism of Action
IL-2 Immunotherapy and Neuroinflammation
This trial investigates low-dose interleukin-2 (IL-2) immunotherapy as a novel approach to modulate [neuroinflammation](/mechanisms/neuroinflammation) in [Alzheimer's disease](/diseases/alzheimers-disease). The rationale stems from growing recognition that immune dysregulation plays a central role in AD pathogenesis.
Immune Modulation Hypothesis
Low-dose IL-2 therapy is based on the understanding that:
Regulatory T-cell (Treg) Enhancement — Low-dose IL-2 preferentially expands regulatory T cells, which are essential for maintaining immune homeostasis[@klatzmann2015]. In Alzheimer's disease, Tregs are often numerically and functionally deficient, contributing to unchecked neuroinflammation[@sakaguchi2010].
...
IL-2 Immunotherapy for Alzheimer's Disease Neuroinflammation (NCT06384378)
| Attribute | Details | |-----------|---------| | Phase | Phase 2 | | Status | Recruiting | | Sponsor | The Methodist Hospital Research Institute | | Intervention | Low-dose IL-2 (interleukin-2) immunotherapy | | Indication | Alzheimer's Disease | | Study Design | Randomized, quadruple-blind, parallel assignment | | Enrollment | 40 participants | | Location | Houston Methodist Research Institute, Houston, Texas |
Study Title
Central and Peripheral Immune Cross-talk in Alzheimer's Disease and Their Modulation by a Novel Immunotherapy
Mechanism of Action
IL-2 Immunotherapy and Neuroinflammation
This trial investigates low-dose interleukin-2 (IL-2) immunotherapy as a novel approach to modulate [neuroinflammation](/mechanisms/neuroinflammation) in [Alzheimer's disease](/diseases/alzheimers-disease). The rationale stems from growing recognition that immune dysregulation plays a central role in AD pathogenesis.
Immune Modulation Hypothesis
Low-dose IL-2 therapy is based on the understanding that:
Regulatory T-cell (Treg) Enhancement — Low-dose IL-2 preferentially expands regulatory T cells, which are essential for maintaining immune homeostasis[@klatzmann2015]. In Alzheimer's disease, Tregs are often numerically and functionally deficient, contributing to unchecked neuroinflammation[@sakaguchi2010].
Cytokine Balance Restoration — IL-2 helps restore the balance between pro-inflammatory and anti-inflammatory cytokines. The [neuroinflammation pathway](/mechanisms/neuroinflammation-pathway) in AD is characterized by elevated pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) relative to anti-inflammatory signals.
Microglial Modulation — [Microglia](/cell-types/microglia) are the resident immune cells of the brain and play a dual role in neurodegeneration[@heneka2015]. Low-dose IL-2 may shift [microglia](/cell-types/microglia-neuroinflammation) from a pro-inflammatory (M1) to a neuroprotective (M2-like) phenotype.
TSPO PET Imaging Endpoint
A unique feature of this trial is the use of 11C-ER176, a PET tracer that binds to the 18 kDa translocator protein (TSPO), formerly known as the peripheral benzodiazepine receptor. TSPO is expressed primarily by activated microglia and [astrocytes](/entities/astrocytes), making it a validated biomarker of brain inflammation[@cosenzanashat2011].
11C-ER176 provides quantitative measures of TSPO binding (VT/fP)
Allows voxel-wise, regional, and total brain assessment of neuroinflammation
Enables direct visualization of treatment effects on glial activation
Study Design
Interventional Arms
| Arm | Intervention | Dosing Frequency | |-----|--------------|------------------| | Active Comparator 1 | IL-2 | Every 2 weeks | | Active Comparator 2 | IL-2 | Every 4 weeks | | Placebo Control | Placebo | Matching schedule |
Blinding
The study employs quadruple blinding, meaning that participants, care providers, investigators, and outcome assessors are all blinded to treatment assignment. This minimizes bias in both subjective and objective outcome measures.
Outcome Measures
Primary Outcomes (36-month timeframe)
Blood inflammation biomarker levels — Plasma chemokine and cytokine changes
Brain TSPO VT/fP — Measured with 11C-ER176 PET imaging (voxel-wise, regional, and total brain)
Rationale for Primary Endpoints
The combination of peripheral and central biomarkers with direct imaging of neuroinflammation provides a comprehensive assessment of IL-2's immunomodulatory effects. This is particularly important given the growing recognition of the [gut-brain axis](/entities/gut-brain-axis) and central-peripheral immune cross-talk in neurodegeneration.
Eligibility Criteria
Inclusion Criteria
Age: 50-86 years
Diagnosis: Probable Alzheimer's disease per NIA-AA criteria
Cognitive status: MMSE between 12-26 (mild to moderate dementia)
Laboratory values: Specific requirements for bilirubin, ALT, AST, albumin, creatinine, WBC, platelets, hematocrit, INR
Medications: Stable chronic medications for 30+ days
Language/education: English speaking, 8+ years formal education
Active major depression, schizophrenia, or bipolar disorder
Uncontrolled medical conditions
Recent cancer (within specified timeframe)
Contraindication to lumbar puncture
Other factors precluding safe participation
Clinical Context
IL-2 Immunotherapy in Neurodegeneration
This trial represents an emerging therapeutic approach that draws on experience from:
Cancer immunotherapy — IL-2 has been used for decades in cancer treatment, particularly for melanoma and renal cell carcinoma
Autoimmune diseases — Low-dose IL-2 has shown promise in systemic lupus erythematosus, type 1 diabetes, and other autoimmune conditions[@rosenzwajg2019]
The translation to Alzheimer's disease follows the immunomodulation rather than immunosuppression paradigm, seeking to restore rather than suppress immune function.
Comparison to Other Neuroinflammation-Targeting Approaches
The sponsor, [Houston Methodist Research Institute](/institutions/houston-methodist-research-institute), is a leading academic medical center with expertise in Alzheimer's disease clinical trials and neuroimaging.
Related Pages
[Neuroinflammation in Alzheimer's Disease](/mechanisms/neuroinflammation)
[Microglia in Neurodegeneration](/cell-types/microglia)
[TSPO Imaging in Neuroinflammation](/technologies/pet-neuroinflammation-imaging)
[Regulatory T Cells in Neurodegeneration](/cell-types/regulatory-t-cells)
[Cytokine Networks in Alzheimer's Disease](/mechanisms/cytokine-signaling-pathway)
[Houston Methodist Research Institute](/institutions/houston-methodist-research-institute)
[Houston Methodist Research Institute](https://www.houstonmethodist.org/research/)
[NIA-AA Criteria for Alzheimer's Disease](https://www.niaaa.nih.gov/research/alzheimers-disease-diagnostic-guidelines)
References
[Klatzmann D, Abbas AK, The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases (2015)](https://pubmed.ncbi.nlm.nih.gov/25882245/)
[Sakaguchi S, Miyara M, Costantino CM, Hafler DA, FOXP3+ regulatory T cells in the human immune system (2010)](https://pubmed.ncbi.nlm.nih.gov/20559327/)
[Heneka MT, et al, Neuroinflammation in Alzheimer's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25792098/)
[Cosenza-Nashat M, et al, Alterations in the peripheral benzodiazepine receptor in neurodegenerative diseases (2011)](https://pubmed.ncbi.nlm.nih.gov/21666537/)
[Rosenzwajg M, et al, Low-dose IL-2 in patients with active systemic lupus erythematosus: a phase I/IIa clinical trial (2019)](https://pubmed.ncbi.nlm.nih.gov/31235699/)