A Phase IIa Multi-Center Study of 18F-FDG PET, Safety, and Tolerability of AZD0530 in Mild Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Drug: PlaceboDrug: AZD0530 100mg dailyDrug: AZD0530 125mg daily
- Registration Number
- NCT02167256
- Lead Sponsor
- Yale University
- Brief Summary
AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment for malignancies because these kinases play a role in tumor invasion and proliferation. However, the Src family kinases (SFKs) are highly expressed in brain and have major effects on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK, namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß) peptide from Alzheimer's disease (AD). Genetic deletion of Fyn rescues AD deficits in preclinical models. This clinical trial will test the potential benefit of AZD0530 for Alzheimer's disease modification.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZD0530 100mg daily AZD0530 125mg daily Patients in the experimental group (50%) will be started on this dose. After 2 weeks, patients with a plasma drug level of \<100ng/ml will receive 125mg AZD0530 daily and remain in the same experimental group as patient receiving 100mg daily. AZD0530 Placebo Placebo 50% of patients will receive placebo treatment for the duration of the study, AZD0530 100mg daily AZD0530 100mg daily Patients in the experimental group (50%) will be started on this dose. After 2 weeks, patients with a plasma drug level of \<100ng/ml will receive 125mg AZD0530 daily and remain in the same experimental group as patient receiving 100mg daily.
- Primary Outcome Measures
Name Time Method Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging 12 months Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
Number of Participants With One or More Serious/Other Adverse Events Subjects With Mild AD as Assessed by Analysis of Adverse Events, Including Symptoms, and Abnormal Findings on Physical and Neurological Examinations, and Standard Labs. 12 months Assessment of any adverse effects between drug and placebo-treated subjects
- Secondary Outcome Measures
Name Time Method Percent Change in Brain Volume Before and After Treatment 12 months Change in volume of pre-defined brain regions between baseline and 12 months of treatment.
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function 12 months The change in cognitive function between baseline and 12 months will be measured by the following tests:
1. Alzheimer Disease Assessment Scale - Cognitive 11 (ADAS-cog11). Measures: Cognitive function Maximum score: 70; Minimum score: 0. Higher score equals worse cognitive function
2. Mini-Mental State Examination (MMSE) Measures: Cognitive Function Maximum score: 30; Minimum score: 0. Higher score equal better cognitive function
3. Alzheimer Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Measures: Ability to perform routine daily activities Maximum score: 78; Minimum score: 0. Higher score equals better ability to perform activities of daily living
4. Clinical Dementia Rating Sum of Boxes (CDR-SO) Measures: Dementia severity Maximum score: 18; Minimum score: 0. Higher score equals more severe dementia.Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging 12 months The results from the primary outcome with brain FDG-PET imaging was analyzed by ApoE genotype. Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42) 12 months Measure concentration of Tau and Amyloid-beta 1-42 biomarkers in the cerebrospinal fluid between baseline and 12 months of treatment
Trial Locations
- Locations (22)
Wien Center for Clinical Research/Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
University of South Florida - Health Byrd Alzheimer Institute
🇺🇸Tampa, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Michigan, Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
University of British Columbia, Clinic for AD & Related Disorders
🇨🇦Vancouver, British Columbia, Canada
Yale Alzheimer's Disease Research Unit
🇺🇸New Haven, Connecticut, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
Roper St. Francis Hospital
🇺🇸Charleston, South Carolina, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
University of Pittsburgh, Alzheimer's Disease Research Center
🇺🇸Pittsburgh, Pennsylvania, United States