Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

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).

Study Overview

• Status: Withdrawn
• Conditions: Cognitive Dysfunction; Alzheimer's Disease
• Intervention / Treatment: Drug: Formoterol A; Other: Formoterol B (placebo)

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Palo Alto Veterans Institute for Research
• Collaborators: Alzheimer's Association; Mylan Inc.
• Investigators: Principal Investigator: Ahmad Salehi, M.D.,Ph.D., Stanford Medical School

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: May 19, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (Estimate): July 17, 2015

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: ASJ0015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No subjects enrolled

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No