NCT06096090

Brief Summary

Neuroinflammation is a significant component of Alzheimer disease (AD). Our group recently demonstrated that regulatory T cells (Tregs) have a compromised phenotype and reduced suppressive function in AD patients, skewing the immune system toward a proinflammatory status and potentially contributing to disease progression. Low dose interleukin-2 (IL-2) is now viewed as a promising immunoregulatory drug with the capacity to selectively expand and restore functional Tregs. This study is a phase II, randomized, double-blind, placebo-controlled study to assess low dose IL-2 therapy in AD patients. Up to 40 Alzheimer's disease patients in the mild- to moderate clinical dementia stages (MMSE scores: 12-26) will be randomized to five-day-courses of subcutaneous IL-2 or placebo for a total of 6 months. We will evaluate the safety and tolerability of IL-2 treatment and the possible effects of IL-2 treatment on peripheral and central inflammation. The expected time participants will be in the study is 30 weeks.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for phase_2 alzheimer-disease

Timeline
Completed

Started Jan 2022

Longer than P75 for phase_2 alzheimer-disease

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2022

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

October 17, 2023

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 23, 2023

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2025

Completed
Last Updated

May 23, 2024

Status Verified

May 1, 2024

Enrollment Period

4 years

First QC Date

October 17, 2023

Last Update Submit

May 22, 2024

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

  • To assess the safety and the tolerability of IL-2 in AD patients

    Primary endpoint: \- Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology)

    6 months treatment phase

Secondary Outcomes (1)

  • To investigate the impact of IL-2 administration on the blood Treg population in AD patients

    6 months treatment phase

Study Arms (3)

Aldesleukin every 4 weeks

ACTIVE COMPARATOR
Drug: Interleukin-2

Aldesleukin every 2 weeks

ACTIVE COMPARATOR
Drug: Interleukin-2

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

Interleukin-2DRUG

Low dose Interleukin-2 (Aldesleukin) administration to expand Regulatory T cells

Aldesleukin every 2 weeksAldesleukin every 4 weeks
PlaceboDRUG

Placebo administration

Placebo

Eligibility Criteria

Age50 Years - 86 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of probable Alzheimer disease according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
  • Male or female age 50 to 86 years
  • MMSE between 12-26
  • Total bilirubin less than or equal to 1.5mg/dL
  • Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) less than or equal to two times normal,
  • Albumin greater than or equal to 3.0mg/dL
  • Serum creatinine less than or equal to 1.5 mg/dL
  • White Blood Count (WBC) \>3,500/mm3; platelets \>100,000/mm3; hematocrit (HCT) \>32%.
  • 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.
  • 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

You may not qualify if:

  • Serious, active bacterial, fungal or viral infection, active or latent tuberculosis
  • History of severe pulmonary dysfunction
  • 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
  • History of bowel ischemia/perforation, or GI bleeding requiring surgery
  • 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, Jacob-Creutzfeld Disease, 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
  • 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.
  • Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Houston Methodist Research Institute

Houston, Texas, 77030, United States

RECRUITING

Related Publications (1)

  • Faridar A, Gamez N, Li D, Wang Y, Boradia R, Thome AD, Zhao W, Beers DR, Thonhoff JR, Nakawah MO, Roman GC, Volpi JJ, Toledo JB, George M, Davis CS, Pascual B, Grundman M, Masdeu JC, Appel SH. Low-dose interleukin-2 in patients with mild to moderate Alzheimer's disease: a randomized clinical trial. Alzheimers Res Ther. 2025 Jul 4;17(1):146. doi: 10.1186/s13195-025-01791-x.

    PMID: 40615880DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

InterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological Factors

Central Study Contacts

Alireza Faridar, MD

CONTACT

7134411150afaridar@houstonmethodist.org

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

October 17, 2023

First Posted

October 23, 2023

Study Start

January 1, 2022

Primary Completion

December 30, 2025

Study Completion

December 30, 2025

Last Updated

May 23, 2024

Record last verified: 2024-05

Data Sharing

IPD Sharing
Will share

Locations

US(1)