IL-2 for Alzheimer's Disease

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: The Methodist Hospital Research Institute

Must be taking: Stable AD meds

Must not be taking: Antipsychotics, Antiepileptics, Corticosteroids, others

Disqualifiers: Infections, Cardiac dysfunction, Cancer, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications, but you need to be on a stable dose of any medications affecting cognition for at least 4 weeks before the trial and remain stable during the study. Some medications, like certain antipsychotics and antiepileptics, are restricted, so check with the trial team about your specific medications.

What evidence supports the effectiveness of the drug IL-2 for treating Alzheimer's disease?

Research suggests that low-dose IL-2 can help balance certain immune cells, which may reduce brain inflammation and slow cognitive decline in Alzheimer's disease, based on studies in mice. ^{1 2 3 4 5}

Is IL-2 generally safe for humans?

IL-2 can have serious side effects, including fever, low blood pressure, heart issues, kidney problems, and neurological effects like confusion and seizures. These side effects are often reversible but can be severe, so IL-2 should be given in a specialized care setting by trained professionals. ^{6 7 8 9 10}

How does the drug IL-2 differ from other Alzheimer's treatments?

IL-2 (Interleukin-2) is unique because it is a cytokine (a type of protein important in cell signaling) that may help modulate the immune response in Alzheimer's disease, unlike most current treatments that primarily focus on managing symptoms or targeting amyloid plaques in the brain. ^{3 11 12 13 14}

Research Team

Eligibility Criteria

This trial is for individuals aged 50-86 with mild to moderate Alzheimer's Disease (AD), as indicated by MMSE scores of 12-26. Participants must have a diagnosis according to NIA-AA criteria, speak English, and have at least eight years of education. They should be stable on current medications for other conditions and meet specific health requirements related to liver function, blood counts, and kidney function.

Inclusion Criteria

Your albumin level is 3.0mg/dL or higher.

English language speaking

Formal education of eight or more years

Exclusion Criteria

I do not have any serious infections or tuberculosis.

You have certain heart or blood pressure issues, uncontrolled diabetes, recent cancer history, hepatitis, certain disabilities, or are taking specific medications or drugs that may make you unsuitable for the study.

I do not have severe heart problems like recent heart attacks or uncontrolled heart rhythm issues.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive five-day-courses of subcutaneous IL-2 or placebo for a total of 6 months

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Interleukin-2 (Cytokine Therapy)

Trial Overview The study tests low dose Interleukin-2 (IL-2) against a placebo in AD patients. It's a phase II trial where participants are randomly assigned to receive either IL-2 or placebo via subcutaneous injections over six months. The aim is to assess the safety of IL-2 therapy and its effects on inflammation in both the brain and body.

Participant Groups

Group I: Aldesleukin every 4 weeks Active Control 1 Intervention

Group II: Aldesleukin every 2 weeks Active Control 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Dr. John P. Cooke

The Methodist Hospital Research Institute

Chief Medical Officer since 2013

MD, PhD

Dr. Jenny Chang

The Methodist Hospital Research Institute

Chief Executive Officer

MBBChir from University of Cambridge, MHCM from Johns Hopkins University

Findings from Research

The TNF-α-308 G/A gene polymorphism is significantly associated with an increased risk of late-onset Alzheimer's disease (LOAD), suggesting it may influence the brain's inflammatory response in affected individuals.

In contrast, the TNF-α-863 C/A polymorphism does not show a significant association with LOAD, indicating that not all TNF-α gene variations impact the disease risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic association of TNF-α-308 G/A and -863 C/A polymorphisms with late onset Alzheimer's disease in Azeri Turk population of Iran. Ardebili, SM., Yeghaneh, T., Gharesouran, J., et al.[2021]

In APP/PS1 mice, a significant imbalance between regulatory T (Treg) cells and IL-17-producing helper T (Th17) cells was observed during the progression of Alzheimer's disease, particularly at the middle disease stage.

Low-dose recombinant human IL-2 treatment effectively restored the balance of Treg and Th17 cells, reduced neuroinflammation, decreased Aβ plaque deposition, and slowed cognitive decline, suggesting its potential as a novel immunotherapy for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose IL-2 Treatment Rescues Cognitive Deficits by Repairing the Imbalance Between Treg and Th17 Cells at the Middle Alzheimer's Disease Stage. Yuan, L., Xie, L., Zhang, H., et al.[2023]

Recombinant interleukin-2 is an effective immunomodulating agent that has shown promising results in treating renal cell carcinoma and melanoma, particularly in patients who do not respond well to conventional therapies.

While it can lead to significant adverse effects like hypotension and renal dysfunction, these effects are generally reversible, and its administration requires careful monitoring in a critical-care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interleukin-2: a biological response modifier. Kintzel, PE., Calis, KA.[2007]

Chronic treatment with high doses of recombinant interleukin-2 in old mice led to significant impairments in memory functions and notable neuronal cell loss specifically in the hippocampus, indicating potential neurotoxic effects in older populations.

In contrast, adult mice treated with interleukin-2 did not show any differences in memory performance or neuron density compared to controls, suggesting that the negative effects of this treatment may be age-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice. Nemni, R., Iannaccone, S., Quattrini, A., et al.[2019]

References

1. India pubmed.ncbi.nlm.nih.gov

Genetic association of TNF-α-308 G/A and -863 C/A polymorphisms with late onset Alzheimer's disease in Azeri Turk population of Iran. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Low-dose IL-2 Treatment Rescues Cognitive Deficits by Repairing the Imbalance Between Treg and Th17 Cells at the Middle Alzheimer's Disease Stage. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Lymphokine production in patients with Alzheimer's disease. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Focusing on IL-1-promotion of beta-amyloid precursor protein synthesis as an early event in Alzheimer's disease. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease. [2019]

6. France pubmed.ncbi.nlm.nih.gov

[Adverse effects of interleukin 2]. [2009]

7. United States pubmed.ncbi.nlm.nih.gov

Recombinant interleukin-2: a biological response modifier. [2007]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Neuropsychological and neurophysiological assessment of the central effects of interleukin-2 administration. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Multiple cerebral lesions complicating therapy with interleukin-2. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Interleukin-1, neuroinflammation, and Alzheimer's disease. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Association between interleukin-1A polymorphism and cerebral amyloid angiopathy-related hemorrhage. [2016]

13. Germany pubmed.ncbi.nlm.nih.gov

Gene dose-dependent association of interleukin-1A [-889] allele 2 polymorphism with Alzheimer's disease. [2006]

14. Poland pubmed.ncbi.nlm.nih.gov

Polymorphism 174 G/C of interleukin 6 gene in Alzheimer's disease--preliminary report. [2015]