Clinical trial NCT02500784: Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
Official title: Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Alzheimer's Disease
Cognitive Dysfunction
Lead sponsor: Palo Alto Veterans Institute for Research
Sponsor class: OTHER
Collaborators: name: Alzheimer's Association
name: Mylan Inc.
First posted: 2015-07-17
Enrollment: 0
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cognition Evaluation
timeFrame: 1 Month
measure: Brain-derived neurotrophic factor (BDNF) Evaluation
timeFrame: Baseline and month 16
Secondary outcomes:
measure: Amyloid accumulation
timeFrame: Baseline and month 16
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
Study officials:
affiliation: Stanford Medical School
name: Ahmad Salehi, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: