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Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT02500784
Recruitment Status : Suspended (Funding ran out before study started, prior PI left institution.)
First Posted : July 17, 2015
Last Update Posted : April 3, 2019
Sponsor:
Collaborators:
Alzheimer's Association
Mylan Inc.
Information provided by (Responsible Party):
J. Wesson Ashford, VA Palo Alto Health Care System

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 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


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




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



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02500784


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

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Responsible Party: J. Wesson Ashford, Clinical Professor, VA Palo Alto Health Care System
ClinicalTrials.gov Identifier: NCT02500784     History of Changes
Other Study ID Numbers: ASJ0015
First Posted: July 17, 2015    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

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

Additional relevant MeSH terms:
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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
Adrenergic Agents
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
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action