Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
Primary Purpose
Alzheimer's Disease, Cognitive Dysfunction
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Formoterol A
Formoterol B (placebo)
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease
Eligibility 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.
Sites / Locations
- VA Palo Alto Health Care System
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Formoterol A
Formoterol B
Arm Description
12 months, formoterol, 20microgram/2ml, inhaler, BID
12 months, normal saline, 2ml, inhaler, BID
Outcomes
Primary Outcome Measures
Cognition Evaluation
Participants will be administered the CANTAB every month for 16 months
Brain-derived neurotrophic factor (BDNF) Evaluation
Samples of Plasma and Cerebral Spinal Fluid Biomarkers will be taken at baseline and month 16
Secondary Outcome Measures
Amyloid accumulation
Molecular Imaging will be taken at baseline and month 16
Full Information
NCT ID
NCT02500784
First Posted
May 19, 2015
Last Updated
September 14, 2020
Sponsor
Palo Alto Veterans Institute for Research
Collaborators
Alzheimer's Association, Mylan Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02500784
Brief Title
Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
Official Title
Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Funding ran out before study started, prior PI left institution.
Study Start Date
January 2023 (Anticipated)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Palo Alto Veterans Institute for Research
Collaborators
Alzheimer's Association, Mylan Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease, Cognitive Dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Formoterol A
Arm Type
Active Comparator
Arm Description
12 months, formoterol, 20microgram/2ml, inhaler, BID
Arm Title
Formoterol B
Arm Type
Placebo Comparator
Arm Description
12 months, normal saline, 2ml, inhaler, BID
Intervention Type
Drug
Intervention Name(s)
Formoterol A
Other Intervention Name(s)
Performist
Intervention Description
20mg/2mL, BID inhaler for 12 months: until progression or unacceptable toxicity develops.
Intervention Type
Other
Intervention Name(s)
Formoterol B (placebo)
Intervention Description
2mL, BID inhaler for 12 months
Primary Outcome Measure Information:
Title
Cognition Evaluation
Description
Participants will be administered the CANTAB every month for 16 months
Time Frame
1 Month
Title
Brain-derived neurotrophic factor (BDNF) Evaluation
Description
Samples of Plasma and Cerebral Spinal Fluid Biomarkers will be taken at baseline and month 16
Time Frame
Baseline and month 16
Secondary Outcome Measure Information:
Title
Amyloid accumulation
Description
Molecular Imaging will be taken at baseline and month 16
Time Frame
Baseline and month 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmad Salehi, M.D.,Ph.D.
Organizational Affiliation
Stanford Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Palo Alto Health Care System
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No subjects enrolled
Learn more about this trial
Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease
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