Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT02500784
• Recruitment Status: Withdrawn
• First Posted: July 17, 2015
• Last Update Posted: September 16, 2020
• Sponsor: Palo Alto Veterans Institute for Research
• Collaborators: Alzheimer's Association; Mylan Inc.
• Information provided by (Responsible Party): J. Wesson Ashford, VA Palo Alto Health Care System

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease; Cognitive Dysfunction	Drug: Formoterol A; Other: Formoterol B (placebo)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
• Estimated Study Start Date: January 2023
• Estimated Primary Completion Date: April 2025
• Estimated Study Completion Date: July 2025

Arms and Interventions

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 Name: Performist
Placebo Comparator: Formoterol B; 12 months, normal saline, 2ml, inhaler, BID	Other: Formoterol B (placebo); 2mL, BID inhaler for 12 months

Outcome Measures

Primary Outcome Measures :

1. Cognition Evaluation [ Time Frame: 1 Month ]
   Participants will be administered the CANTAB every month for 16 months
2. Brain-derived neurotrophic factor (BDNF) Evaluation [ Time Frame: Baseline and month 16 ]
   Samples of Plasma and Cerebral Spinal Fluid Biomarkers will be taken at baseline and month 16

Secondary Outcome Measures :

1. Amyloid accumulation [ Time Frame: Baseline and month 16 ]
   Molecular Imaging will be taken at baseline and month 16

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, California

VA Palo Alto Health Care System

Palo Alto, California, United States, 94304

Sponsors and Collaborators

Palo Alto Veterans Institute for Research

Alzheimer's Association

Mylan Inc.

Investigators

• Principal Investigator: Ahmad Salehi, M.D.,Ph.D.; Stanford Medical School

More Information

• Responsible Party: J. Wesson Ashford, Clinical Professor, VA Palo Alto Health Care System
• ClinicalTrials.gov Identifier: NCT02500784
• Other Study ID Numbers: ASJ0015
• First Posted: July 17, 2015
• Last Update Posted: September 16, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No subjects enrolled

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action