Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to test the effects of long-term therapeutic doses of formoterol, on a) cerebrospinal fluid (CSF) tau levels, and Amyloid Beta protein 40/42 levels in the CSF, and b) cognitive function in people with mild to moderate Alzheimer' Disease (AD).

Detailed Description
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The purpose of this study is to test the effects of long-term therapeutic doses of formoterol, on a) cerebrospinal fluid CSF tau levels, and A-beta amyloid protein 40/42 levels, and b) cognitive function: NE-ergic neurons undergo significant degeneration in AD. This system plays a significant role in cognition. Recent studies have indicated that increasing NE levels in the brain would significantly improve microglia migration and clearance of A-beta amyloid protein 40/42 levels in mouse models of AD. The investigators plan to test whether long- term daily treatment with inhaled formoterol solution would improve the structure and function of hippocampal neurons in AD. Study Design: Randomization and initiation of experimental treatment: All participants will be given formoterol daily for 52 weeks. The active regimen will be initiated as (20 micro gram, BID). The dose will be decreased if there is evidence of side effects, including cardiac or respiratory alteration changes, gastro-intestinal disturbances or neurological issues.

Official Title
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Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

Conditions
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Alzheimer's Disease, Cognitive Dysfunction

Intervention / Treatment
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* Drug: Formoterol A
* Other: Formoterol B (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 50-85, Mild-to-moderate AD (NINCDS/ADRDA criteria for probable AD will be used to establish AD diagnosis). MMSE 16-26. Exclusion Criteria: Non-AD dementia or significant neurological disease such as Parkinson's disease, stroke, brain tumor,multiple sclerosis, seizure disorder, focal brain lesion, or head injury with loss of consciousness. Hypothyroidism, congestive heart failure (New York Heart Association Class III or IV), significant extrapyramidal symptoms on neurological examination, serum creatinine>1.3 mg/dl, significant arrhythmias or conduction defect abnormalities on ECG, Use of another beta2 adrenergic drug within the last 2 months. Residence in a long-term care facility. Evidence of any significant clinical disorder or laboratory finding that renders the person unsuitable for receiving an investigational new drug. Known hypersensitivity or prior exposure to formoterol. Active asthma or family history of asthma.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Formoterol A<br>12 months, formoterol, 20microgram/2ml, inhaler, BID | Drug: Formoterol A<br>* 20mg/2mL, BID inhaler for 12 months: until progression or unacceptable toxicity develops.<br>* Other names: Performist;|
| Placebo Comparator: Formoterol B<br>12 months, normal saline, 2ml, inhaler, BID | Other: Formoterol B (placebo)<br>* 2mL, BID inhaler for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition Evaluation | Participants will be administered the CANTAB every month for 16 months | 1 Month | 
| Brain-derived neurotrophic factor (BDNF) Evaluation | Samples of Plasma and Cerebral Spinal Fluid Biomarkers will be taken at baseline and month 16 | Baseline and month 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amyloid accumulation | Molecular Imaging will be taken at baseline and month 16 | Baseline and month 16 |