Systemic and Central Inflammation in AD

NCT06384378 | Recruiting Phase 2 FDA Drug

• 1 other identifier: FP00006640
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammation could provide a new focus for therapeutic intervention. In this study, we will measure blood and cerebrospinal fluid (CSF) inflammation biomarkers and compare them to measurements of brain glial activation obtained by positron emission tomography (PET). In addition, we will determine the effect of low-dose interleukin-2 (IL-2) immunotherapy, given over 22 weeks, on these inflammation biomarkers.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• Blood inflammation biomarker levels

  To monitor plasma inflammatory chemokine and cytokine changes following IL-2 immunotherapy

  36 months

• CSF inflammation biomarker levels

  To monitor CSF inflammatory chemokine and cytokine changes following IL-2 immunotherapy

  36 months

• Voxel-wise, regional and total brain TSPO VT/fP measured with 11C-ER176 PET

  To evaluate the effects of IL-2 immunotherapy on brain glial activation, measured by Protein 18kDa Translocator Positron-Emission Tomography (TSPO PET)

  36 months

Study Arms (3)

IL-2 every 4 weeks

ACTIVE COMPARATOR

Aldesleukin every 4 weeks

Drug: 11C-ER176

IL-2 every 2 weeks

ACTIVE COMPARATOR

Aldesleukin every 2 weeks

Drug: 11C-ER176

Placebo

PLACEBO COMPARATOR

Drug: 11C-ER176

Interventions

11C-ER176 DRUG

ER176 is a PET tracer that binds to the 18 kDa translocator protein (TSPO), which is expressed by activated microglia and astrocytes and is therefore an index of brain inflammation.

IL-2 every 2 weeks; IL-2 every 4 weeks; Placebo

Eligibility Criteria

• Age: 50 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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:
• 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.).

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Research Institute

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Alireza Faridar

CONTACT

7134411150; afaridar@houstonmethodist.org

Maria B Pascual

CONTACT

bpascual@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: March 17, 2023
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: April 25, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)