Low Dose IL2 Immunotherapy in AD

April 19, 2023 updated by: Alireza Faridar, The Methodist Hospital Research Institute

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

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.

Study Overview

Status

Completed

Conditions

Alzheimer Disease

Intervention / Treatment

Drug: Aldesleukin

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Texas
  - Houston, Texas, United States, 77030
    - Alireza Faridar

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Description

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%.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 Time Frame: 4 months treatment phase	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. Time Frame: 4 months treatment phase	Secondary endpoints: - Change in Treg percentage out of total # of CD4 cells from baseline to month 4	4 months treatment phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Methodist Hospital Research Institute

Investigators

Principal Investigator: Alireza Faridar, Houston Methodist Neurological Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 19, 2019

Primary Completion (Actual)

April 27, 2022

Study Completion (Actual)

April 27, 2022

Study Registration Dates

First Submitted

March 27, 2023

First Submitted That Met QC Criteria

April 19, 2023

First Posted (Actual)

April 20, 2023

Study Record Updates

Last Update Posted (Actual)