Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

Phase 2

Withdrawn

• Conditions: Alzheimer's Disease; Cognitive Dysfunction
• Interventions: Drug: Formoterol A; Other: Formoterol B (placebo)

• Registration Number: NCT02500784
• Lead Sponsor: Palo Alto Veterans Institute for Research

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.

Study Timeline

• Study First Submitted: 2015-05-19
• Study First Submitted QC: 2015-07-15
• Study First Posted: 2015-07-17
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-14
• Last Update Posted: 2020-09-16
• Study Start: 2023-01
• Primary Completion: 2025-04
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Formoterol A	Formoterol A	12 months, formoterol, 20microgram/2ml, inhaler, BID
Formoterol B	Formoterol B (placebo)	12 months, normal saline, 2ml, inhaler, BID

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Amyloid accumulation	Baseline and month 16	Molecular Imaging will be taken at baseline and month 16

Trial Locations

Locations (1)

VA Palo Alto Health Care System; 🇺🇸 Palo Alto, California, United States