Alzheimer's Disease, Cognitive Dysfunction
Conditions
Brief summary
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
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.
Interventions
DRUGFormoterol A
20mg/2mL, BID inhaler for 12 months: until progression or unacceptable toxicity develops.
OTHERFormoterol B (placebo)
2mL, BID inhaler for 12 months
Sponsors
Alzheimer's Association
Mylan Inc.
Palo Alto Veterans Institute for Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognition Evaluation | 1 Month | Participants will be administered the CANTAB every month for 16 months |
| Brain-derived neurotrophic factor (BDNF) Evaluation | Baseline and month 16 | Samples of Plasma and Cerebral Spinal Fluid Biomarkers will be taken at baseline and month 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amyloid accumulation | Baseline and month 16 | Molecular Imaging will be taken at baseline and month 16 |
Countries
United States
Outcome results
None listed