Interleukine-2 (IL-2) Plus Semaglutide in Alzheimer's Disease

Conditions

• Alzheimer Dementia (AD)

Eligibility Criteria

Sex

ALL

Age

50 Years - 86 Years

Healthy Volunteers

Not accepted

Interventions

• IL-2 (Aldesleukin) — DRUG
  aldesleukin administered subcutaneously once daily for 5 consecutive days, repeated every 4 weeks for six cycles
• Semaglutide Plus IL-2 — DRUG
  Combination therapy with LD IL-2 plus subcutaneous semaglutide
• Placebo — DRUG
  Placebo

Study Details

Alzheimer's disease (AD) is the most common cause of dementia. Despite major research efforts, effective treatments that slow or stop disease progression remain limited. Growing evidence suggests that inflammation in the brain and the body plays a key role in the onset and progression of AD. In particular, immune cells called regulatory T cells (Tregs), which normally help control inflammation, are impaired in AD individuals. This leads to increased activity of harmful immune pathways that worsen brain injury. Interleukin-2 (IL-2) is a drug that can restore the function of Tregs. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are a class of drugs currently used to treat diabetes and obesity. Beyond their metabolic effects, GLP-1RAs also reduce inflammation, protect brain cells, and improve cellular energy balance. Laboratory studies, including our own, show that combining IL-2 with semaglutide has stronger effects than either drug alone. Together, they enhance Treg function, dampen harmful inflammatory responses, and improve cell survival. These findings support testing IL-2 plus semaglutide as a novel combination therapy for AD. We now propose a clinical trial to evaluate the safety, feasibility, and biological effects of this strategy. The study will enroll 30 individuals with AD, ages 50 to 86, who have a confirmed diagnosis by amyloid PET brain imaging and a Mini-Mental State Exam score between 16 and 26. Participants will be randomly assigned to one of three groups: (1) placebo, (2) low-dose IL-2 alone, or (3) IL-2 combined with semaglutide. Throughout the trial, participants will undergo regular medical exams, blood tests, and safety monitoring. We will measure how the treatment affects Tregs and other immune cells, inflammatory markers in blood and CSF, and established Alzheimer's biomarkers such as amyloid beta, tau, and neurofilament light chain. Cognitive and functional assessments will also be conducted to explore potential benefits on memory and daily living skills. If successful, this study will provide the first evidence that a dual immunotherapeutic strategy can safely modify disease-related processes in AD. Such findings would lay the foundation for larger clinical trials and could open the door to a new, multimodal approach to slowing or preventing Alzheimer's progression.

Key Dates

Start date

Jul 31, 2026

Status verified

Jun 2026

Primary completion

Jun 30, 2029

Completion

Dec 31, 2029

Study Design

Enrollment

30 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Placebo Comparator: Placebo
  Placebo Administration
• Active Comparator: Low-dose recombinant human IL-2 (LD IL-2) monotherapy
  Low-dose recombinant human IL-2 (LD IL-2) monotherapy (aldesleukin) administered subcutaneously once daily for 5 consecutive days, repeated every 4 weeks for six cycles.
• Active Comparator: IL-2 Plus Semaglutide combination therapy
  Combination therapy with LD IL-2 on the same schedule as Arm B plus subcutaneous semaglutide, administered with stepwise dose escalation administered once weekly

Primary Outcome Measure

To assess the safety and the tolerability of IL-2 plus Semaglutide in AD patients [ Time Frame: 6 months treatment phase ]

Central Contacts

• Alireza Alireza, MD
  713-441-1150
  [email protected]

Locations (1)

Find similar trials in Houston, TX

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