Systemic and Central Inflammation in AD
Central and Peripheral Immune Cross-talk in Alzheimer's Disease and Their Modulation by a Novel Immunotherapy
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Phase 2
Contacts and Locations
Study Contact
Study Contact
- Name: Alireza Faridar
- Phone Number: 7134411150
- Email: afaridar@houstonmethodist.org
Study Contact Backup
- Name: Maria B Pascual
- Email: bpascual@houstonmethodist.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Houston Methodist Research Institute
-
Contact:
- Alireza Faridar
- Phone Number: 713-441-1150
- Email: afaridar@houstonmethodist.org
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
|
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.
|
|
Active Comparator: IL-2 every 4 weeks
Aldesleukin every 4 weeks
|
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.
|
|
Active Comparator: IL-2 every 2 weeks
Aldesleukin every 2 weeks
|
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.
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Blood inflammation biomarker levels
Time Frame: 36 months
|
To monitor plasma inflammatory chemokine and cytokine changes following IL-2 immunotherapy
|
36 months
|
|
CSF inflammation biomarker levels
Time Frame: 36 months
|
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
Time Frame: 36 months
|
To evaluate the effects of IL-2 immunotherapy on brain glial activation, measured by Protein 18kDa Translocator Positron-Emission Tomography (TSPO PET)
|
36 months
|
Collaborators and Investigators
Sponsor
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Estimated)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
Other Study ID Numbers
- FP00006640
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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