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

Recruiting now · Phase 1/Phase 2 · Has a placebo group

Conditions studied: Alzheimer Dementia (AD)

In brief

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 facts

Study ID

NCT07651319

Run by

The Methodist Hospital Research Institute

People needed

30

Starts

2026-07-01

Expected to finish

2029-12-01

Last updated by the study team

2026-06-16

Who can join

Age: 50 and older, up to 86. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Diagnosis of probable Alzheimer disease according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria13.
• Male or female age 50 to 86 years
• MMSE between 16-26
• Albumin greater than or equal to 3.0mg/dL
• White Blood Count (WBC) >3,500/mm3; platelets >100,000/mm3; hematocrit (HCT) >32%.
• INR<1.4
• If on medications affecting cognition (rivastigmine, galantamine, donepezil, memantine), participants must be on stable dosage for at least 4 weeks prior to screening and should remain at a stable dosage during the course of the study.
• English language speaking
• Formal education of eight or more years
• Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening
• A family member or caretaker who is expected to be consistently available, administer study drugs of IL-2 and attend study visits throughout the study.
• For AD patients with limited decision-making capacity, the legally authorized representative (LAR) should be present and consent based on the patient's best interest.

You may not qualify if…

• Any untreated bacterial, fungal or viral infection
• Renal dysfunction indicated by serum creatinine greater than 1.5 mg/dL
• Hepatic impairment indicated by Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) greater than two times normal
• Clinically significant pulmonary dysfunction, including a history of chronic pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD]) associated with functional limitation, or FEV₁ < 75% of predicted for age and height when pulmonary function testing indicated to evaluate ongoing respiratory symptoms
• Clinically significant cardiac dysfunction, including a history of uncontrolled cardiac arrhythmias, prior cardiac tamponade, or unstable angina or myocardial infarction within 3 months prior to screening, or clinically significant abnormalities on baseline electrocardiogram (ECG). LVEF< 40% in echocardiography if clinically indicated based on ongoing cardiac symptoms or abnormal ECG findings
• Hypersensitivity or allergy to IL-2
• History of severe gastrointestinal disease Hospitalization or change of chronic concomitant medication within one month prior to screening.
• History of hemorrhage or infarct or > 3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor with the exception of small incidental meningiomas) in prior CT or MRI.
• Clinical or laboratory findings consistent with:
• Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeld-Jakob Disease(CJD), Down's syndrome, etc.)
• Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
• Seizure disorder
• History of infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, vitamin B12 or folate deficiency, other laboratory values, etc.)
• Clinically significant abnormal T4 or TSH
• Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:
• Respiratory insufficiency
• Bradycardia (<45/min.) or tachycardia (>100/min.)
• Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg)
• Uncontrolled diabetes defined by HbA1c >8%
• History of cancer within 3 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
• History of organ allografts
• Current treatment with insulin or insulin secretagogues (including sulfonylureas or meglitinides)
• Prior GLP-1 RA administration or natural GLP1 supplements intake within the past 6 months
• Disability that may prevent the patient from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc.).

Where it is running

• Houston Methodist Research Institute — Houston, Texas, United States (enrolling)

Full record on ClinicalTrials.gov

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