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

NCT07651319 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PRO00042175
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Dementia (AD)

Keywords

Alzheimer's Disease; inflammation; Immunotherapy; IL-2; Semaglutide

Outcome Measures

Primary Outcomes (1)

• To assess the safety and the tolerability of IL-2 plus Semaglutide in AD patients

  Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology).

  6 months treatment phase

Secondary Outcomes (1)

• To investigate the impact of IL-2 plus Semaglutide administration on the blood Treg population

  6 months treatment phase

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Placebo Administration

Drug: Placebo

Low-dose recombinant human IL-2 (LD IL-2) monotherapy

ACTIVE COMPARATOR

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.

Drug: IL-2 (Aldesleukin)

IL-2 Plus Semaglutide combination therapy

ACTIVE COMPARATOR

Combination therapy with LD IL-2 on the same schedule as Arm B plus subcutaneous semaglutide, administered with stepwise dose escalation administered once weekly

Drug: Semaglutide Plus IL-2

Interventions

IL-2 (Aldesleukin) DRUG

aldesleukin administered subcutaneously once daily for 5 consecutive days, repeated every 4 weeks for six cycles

Low-dose recombinant human IL-2 (LD IL-2) monotherapy

Placebo DRUG

Placebo

Placebo

Semaglutide Plus IL-2 DRUG

Combination therapy with LD IL-2 plus subcutaneous semaglutide

IL-2 Plus Semaglutide combination therapy

Eligibility Criteria

• Age: 50 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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:

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Research Institute

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Inflammation

Interventions

Interleukin-2; aldesleukin; semaglutide

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Central Study Contacts

Alireza Alireza, MD

CONTACT

713-441-1150; afaridar@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 16, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)