Back to results

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Withdrawn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)

About this trial

This is an interventional treatment trial for Alzheimer's Disease

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Data Monitoring Committee

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

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

IPD Sharing Plan Description

No subjects enrolled

Learn more about this trial

Improving Beta-2 Adrenergic Signaling in Alzheimer's Disease

We'll reach out to this number within 24 hrs