Testing low dose interleukin-2 for Alzheimer’s disease

A Phase II Clinical Trial of Interleukin-2 (IL-2) in Patients With Mild to Moderate Alzheimer's Disease

This study is testing if a low dose of interleukin-2 can help improve the immune system in people with mild to moderate Alzheimer's disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 50 Years to 86 Years
• Sex: All
• Sponsor: The Methodist Hospital Research Institute (Academic / other)
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06096090 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the effects of low dose interleukin-2 (IL-2) therapy on patients with Alzheimer’s disease (AD), focusing on its potential to restore the function of regulatory T cells that are compromised in AD. The study will enroll up to 40 participants with mild to moderate dementia, who will be randomly assigned to receive either IL-2 or a placebo over a six-month period. Researchers will assess the safety, tolerability, and impact of IL-2 on inflammation in both peripheral and central systems. The trial aims to provide insights into the immunoregulatory effects of IL-2 in the context of AD.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 to 86 with a diagnosis of probable Alzheimer’s disease and mild to moderate cognitive impairment.

Not a fit: Patients with severe Alzheimer’s disease or those with significant comorbidities that affect immune function may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve immune function and potentially slow the progression of Alzheimer’s disease.

How similar studies have performed: While the approach of using IL-2 in Alzheimer’s disease is novel, previous studies have shown promise in using immunotherapy for neurodegenerative conditions.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of probable Alzheimer disease according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
2. Male or female age 50 to 86 years
3. MMSE between 12-26
4. Total bilirubin less than or equal to 1.5mg/dL
5. Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) less than or equal to two times normal,
6. Albumin greater than or equal to 3.0mg/dL
7. Serum creatinine less than or equal to 1.5 mg/dL
8. White Blood Count (WBC) \>3,500/mm3; platelets \>100,000/mm3; hematocrit (HCT) \>32%.
9. 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.
10. English language speaking
11. Formal education of eight or more years
12. Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening

Exclusion Criteria:

1. Serious, active bacterial, fungal or viral infection, active or latent tuberculosis
2. History of severe pulmonary dysfunction
3. Severe cardiac dysfunction defined as left ventricular ejection fraction \<40% if an echocardiogram is medically indicated to clarify ongoing symptoms or EKG findings.; a history of non-controlled cardiac arrhythmias; history of cardiac tamponade; Unstable angina or MI in the last 3 months
4. Hypersensitivity or allergy to IL-2
5. History of bowel ischemia/perforation, or GI bleeding requiring surgery
6. Hospitalization or change of chronic concomitant medication within one month prior to screening.
7. 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.
8. Clinical or laboratory findings consistent with:

   1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeld Disease, Down's syndrome, etc.)
   2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
   3. Seizure disorder
   4. History of infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, vitamin B12 or folate deficiency, other laboratory values, etc.)
   5. Clinically significant abnormal T4 or TSH
9. A current DSM-V diagnosis of active major depression, schizophrenia or bipolar disorder. Patients with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.
10. Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:

    1. Respiratory insufficiency
    2. Bradycardia (\<45/min.) or tachycardia (\>100/min.)
    3. 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)
    4. Uncontrolled diabetes defined by HbA1c \>8%
11. 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.
12. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
13. Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.).
14. 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.
15. Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.
16. 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
17. Suspected or known allergy to any components of the study treatments.
18. Intake of investigational drug within the previous 30 days or five half-lives of the investigational drug, whichever is longer.
19. Exposure to passive immunotherapies for AD (e.g. monoclonal antibodies) within the previous 180 days to dosing, and BACE inhibitors within the previous 30 days to dosing.
20. Chronic steroid or interferon therapy
21. 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.
22. Any condition, which in the opinion of the investigator makes the patient unsuitable for inclusion.

Where this trial is running

Houston, Texas

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

Study contacts

• Study coordinator: Alireza Faridar, MD

Conditions Alzheimer Disease