Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02500784
• Other study ID #: ASJ0015
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2023
• Est. completion date: July 2025

Study information

• Verified date: September 2020
• Source: Palo Alto Veterans Institute for Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognitive Dysfunction

Intervention

Drug:
• Formoterol A
20mg/2mL, BID inhaler for 12 months: until progression or unacceptable toxicity develops.

Other:
• Formoterol B (placebo)
2mL, BID inhaler for 12 months

Locations

Country	Name	City	State
United States	VA Palo Alto Health Care System	Palo Alto	California

Sponsors (3)

Lead Sponsor	Collaborator
Palo Alto Veterans Institute for Research	Alzheimer's Association, Mylan Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognition Evaluation	Participants will be administered the CANTAB every month for 16 months	1 Month
Primary	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	Amyloid accumulation	Molecular Imaging will be taken at baseline and month 16	Baseline and month 16