Phase II Clinical Trial of Interleukin-2 in AD

Eligibility 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
• 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.