Phase II Clinical Trial of Interleukin-2 in AD
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Aldesleukin every 4 weeks
|
Drug: Interleukin-2
Low dose Interleukin-2 (Aldesleukin) administration to expand Regulatory T cells
|
| Active Comparator: Aldesleukin every 2 weeks
|
Drug: Interleukin-2
Low dose Interleukin-2 (Aldesleukin) administration to expand Regulatory T cells
|
| Placebo Comparator: Placebo
|
Drug: Placebo
Placebo administration
|
Outcome Measures
Primary Outcome Measures
- To assess the safety and the tolerability of IL-2 in AD patients [6 months treatment phase]
Primary endpoint: - Number of participants with adverse events and with abnormal laboratory findings (serum chemistry, hematology)
Secondary Outcome Measures
- To investigate the impact of IL-2 administration on the blood Treg population in AD patients [6 months treatment phase]
Secondary Endpoint: - Change in Treg percentage out of total CD4 cells
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of probable Alzheimer disease according to National Institute on Aging-Alzheimer's Association (NIA-AA) criteria
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Male or female age 50 to 86 years
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MMSE between 12-26
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Total bilirubin less than or equal to 1.5mg/dL
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Alanine aminotransferase level (ALT) and aspartate aminotransferase (AST) less than or equal to two times normal,
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Albumin greater than or equal to 3.0mg/dL
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Serum creatinine less than or equal to 1.5 mg/dL
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White Blood Count (WBC) >3,500/mm3; platelets >100,000/mm3; hematocrit (HCT) >32%.
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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.
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English language speaking
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Formal education of eight or more years
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Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening
Exclusion Criteria:
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Serious, active bacterial, fungal or viral infection, active or latent tuberculosis
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History of severe pulmonary dysfunction
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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
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Hypersensitivity or allergy to IL-2
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History of bowel ischemia/perforation, or GI bleeding requiring surgery
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Hospitalization or change of chronic concomitant medication within one month prior to screening.
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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.
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Clinical or laboratory findings consistent with:
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Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeld Disease, Down's syndrome, etc.)
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Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
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Seizure disorder
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History of infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, vitamin B12 or folate deficiency, other laboratory values, etc.)
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Clinically significant abnormal T4 or TSH
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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.
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Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:
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Respiratory insufficiency
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Bradycardia (<45/min.) or tachycardia (>100/min.)
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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)
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Uncontrolled diabetes defined by HbA1c >8%
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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.
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History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
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Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.).
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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.
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Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.
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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
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Suspected or known allergy to any components of the study treatments.
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Intake of investigational drug within the previous 30 days or five half-lives of the investigational drug, whichever is longer.
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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.
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Chronic steroid or interferon therapy
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Houston Methodist Research Institute | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- The Methodist Hospital Research Institute
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRO00030798