NCT06096090招募中2 期
A Phase II Clinical Trial of Interleukin-2 (IL-2) in Patients With Mild to Moderate Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- To assess the safety and the tolerability of IL-2 in AD patients
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 86 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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:
- •Respiratory insufficiency
- •Bradycardia (<45/min.) or tachycardia (>100/min.)
- •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)
- •Uncontrolled diabetes defined by HbA1c >8%
- •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.
- •History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
- •Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.).
- •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.
- •Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.
- •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
- •Suspected or known allergy to any components of the study treatments.
- •Intake of investigational drug within the previous 30 days or five half-lives of the investigational drug, whichever is longer.
- •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.
- •Chronic steroid or interferon therapy
- •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.
- •Any condition, which in the opinion of the investigator makes the patient unsuitable for inclusion.
研究组 & 干预措施
Aldesleukin every 4 weeks
Active Comparator
干预措施: Interleukin-2 (Drug)
Aldesleukin every 2 weeks
Active Comparator
干预措施: Interleukin-2 (Drug)
Placebo
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
To assess the safety and the tolerability of IL-2 in AD patients
时间窗: 6 months treatment phase
Primary endpoint: - Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology)
次要结局
- To investigate the impact of IL-2 administration on the blood Treg population in AD patients(6 months treatment phase)
研究者
Alireza Faridar
Assistant Professor
The Methodist Hospital Research Institute
研究点 (1)
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