Alzheimer Dementia (AD)Phase 1/2NCT07651319
Interleukine-2 (IL-2) Plus Semaglutide in Alzheimer's Disease
A Phase 1/2 study testing IL-2 (Aldesleukin) and Semaglutide Plus IL-2 in people with Alzheimer Dementia (AD), run by The Methodist Hospital Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 86 years
- Conditions the study is for
- Alzheimer Dementia (AD)
- What is being tested?
- IL-2 (Aldesleukin) and Semaglutide Plus IL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2026to Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 86 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.).
- Within 4 weeks of screening visit or during the course of the study, concurrent treatment with antipsychotic agents (except risperidone ≤1.5 mg/day, quetiapine ≤100 mg/day, olanzapine ≤5 mg/day, and aripiprazole ≤10 mg/day), antiepileptics (except lamotrigine, gabapentin and pregabalin for nonseizure indications), centrally active anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.), opiate analgesics, systemic corticosteroids, psychostimulants, antiparkinsonian medications (except for non-parkinsonian indications) and mood stabilizers (e.g., valproate, lithium), sedatives, and anxiolytics with the exception that use of short- to medium-acting benzodiazepines for treatment of insomnia is permitted, however, use of sedatives or hypnotics should be avoided for 8 hours before administration of cognitive tests.
- Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.
- Use of concomitant CYP-metabolized medications with a narrow therapeutic index including warfarin, calcineurin inhibitors, or theophylline)
- Suspected or known drug or alcohol abuse, i.e., more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) indicated by elevated MCV significantly above normal value at screening
- Suspected or known allergy to any components of the study treatments.
- Intake of investigational drug within the previous 30 days or five half-lives of the investigational drug, whichever is longer.
- Contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; INR >1.4 or other coagulopathy; platelet count of <100,000/μL; infection at the desired lumbar puncture site; taking anti-coagulant medication within 90 days of screening (Note: low dose aspirin is permitted); suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
- Any condition, which in the opinion of the investigator makes the patient unsuitable for inclusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Houston Methodist Research Institute
Houston, Texas, 77030
Alireza Faridar, MD, 713-441-1150, afaridar@houstonmethodist.org
afaridar@houstonmethodist.org
About this study
Official title: A Phase Ib Clinical Trial, Using Interleukin-2 (IL-2) and Semaglutide in Patients With Alzheimer's Disease
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)
- Being tested
- IL-2 (Aldesleukin), Semaglutide Plus IL-2, Placebo
- Keywords
- Alzheimer's Disease, inflammation, Immunotherapy, IL-2, Semaglutide
- Medical subject headings
- Alzheimer Disease, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-2 (Aldesleukin)Drug
aldesleukin administered subcutaneously once daily for 5 consecutive days, repeated every 4 weeks for six cycles
Semaglutide Plus IL-2Drug
Combination therapy with LD IL-2 plus subcutaneous semaglutide
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Administration Receives: 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. Receives: 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 Receives: Drug: Semaglutide Plus IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the Incidence of Treatment-Emergent Adverse Events of IL-2 plus Semaglutide in AD patients
Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology).
Measured: 6 months treatment phase
Secondary outcomes (1)
The impact of IL-2 plus Semaglutide administration on the blood Treg population
Change in Treg percentage out of total # of CD4 cells from baseline to month 6
Measured: 6 months treatment phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2026
- Study start1 Sep 2026
- Primary completionJun 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Dementia (AD)Studies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07651319
- Sponsor's protocol ID
- PRO00042175
- Status last verified
- Nov 2026
- First submitted
- 2 Jun 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Clinical Trial, Using Interleukin-2 (IL-2) and Semaglutide in Patients With Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07651319
- Acronym / sponsor ID
- PRO00042175
- Conditions
- Alzheimer Dementia (AD)
- Keywords
- Alzheimer's Disease, inflammation, Immunotherapy, IL-2, Semaglutide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Study start
- 1 Sep 2026 (actual)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 16 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo Administration |
| Low-dose recombinant human IL-2 (LD IL-2) monotherapy | Active comparator | Drug: IL-2 (Aldesleukin)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. |
| IL-2 Plus Semaglutide combination therapy | Active comparator | Drug: Semaglutide Plus IL-2Combination therapy with LD IL-2 on the same schedule as Arm B plus subcutaneous semaglutide, administered with stepwise dose escalation administered once weekly |
Who may qualify
- Ages
- 50 to 86 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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%.
Key exclusion criteria (33 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IL-2 (Aldesleukin)aldesleukin administered subcutaneously once daily for 5 consecutive days, repeated every 4 weeks for six cycles | Drug | Low-dose recombinant human IL-2 (LD IL-2) monotherapy |
| Semaglutide Plus IL-2Combination therapy with LD IL-2 plus subcutaneous semaglutide | Drug | IL-2 Plus Semaglutide combination therapy |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Evaluate the Incidence of Treatment-Emergent Adverse Events of IL-2 plus Semaglutide in AD patients
Time frame: 6 months treatment phase
Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology).
1 secondary outcome
The impact of IL-2 plus Semaglutide administration on the blood Treg population
Time frame: 6 months treatment phase
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IL-2 (Aldesleukin) and Semaglutide Plus IL-2 in people with Alzheimer Dementia (AD), run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alireza Alireza, MD (713-441-1150, afaridar@houstonmethodist.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the Incidence of Treatment-Emergent Adverse Events of IL-2 plus Semaglutide in AD patients (time frame: 6 months treatment phase). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026; AzTrials last refreshed its copy on 7 Nov 2026.