Low Dose IL2 Immunotherapy in AD

Study Overview
=================
Brief Summary
-----------------
Neuroinflammation is a significant component of Alzheimer disease (AD). Our data demonstrated compromised regulatory T cells (Tregs) phenotype and suppressive function in AD patients, skewing the immune system toward a proinflammatory status and potentially contributing in disease progression. Low dose interleukin-2 (IL-2) is now viewed as a very promising immunoregulatory drug having the capacity to selectively expand and restore functional Tregs. This study is a phase I open-label study to assess subcutaneous interleukin-2 (IL2) safety and potential efficacy as a Treg inducer in AD. 8 Alzheimer dementia patients with mild clinical dementia will be recruited into the study. The baseline cognitive status will be evaluated in these patients. Monthly five-day-courses of subcutaneous IL2 (1MUI/day) will be administered for a total of 4 months. Changes in Tregs from pre to post injections will be measured during the study period. The expected time participants will be in the study is 6 months.

Official Title
-----------------
Phase I Trial Using Interleukin-2 (IL-2) to Expand Regulatory T Cells in Patients With Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: Aldesleukin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of probable Alzheimer disease according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria13. Male or female age 60 to 86 years Clinical dementia rating scale of 1 Total bilirubin less than or equal to 1.5mg/dL Alanine aminotransferase level (ALT) less than or equal to five times normal, albumin greater than or equal to 3.0gm/dL Serum creatinine less than 1.5 mg/dL English language speaking A family member or caretaker who is expected to be consistently available, administer study drug and attend study visits throughout the study. Exclusion Criteria: Serious, active bacterial, fungal or viral infection Severe pulmonary dysfunction. FEV1 and FVC less than 40% of predicted (or 3 SD below normal) at baseline, If a pulmonary function test is clinically indicated. Hx of intubation for >72 hours. 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 Hypersensitivity or allergy to IL-2 Bowel ischemia/perforation, GI bleeding requiring surgery Resistant seizures, history of coma or toxic psychosis lasting >48 hours Patients with White Blood Count (WBC) <4,000/mm3; platelets <100,000/mm3; hematocrit (HCT) <30%.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 86 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Aldesleukin|Low dose Interleukin-2 (Aldesleukin) administration to expand Regulatory T cells|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and the tolerability of IL-2 in AD patients | Primary endpoints: - Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology). | 4 months treatment phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the impact of low dose IL-2 administration on the blood Treg population in AD patients. | Secondary endpoints: - Change in Treg percentage out of total # of CD4 cells from baseline to month 4 | 4 months treatment phase |