None listed
Conditions
Brief summary
The ApolipoproteinE-e4 allele is the most consistent genetic risk factor associated with sporadic Alzheimer’s Disease (AD). ApolipoproteinE has an important influence on beta-amyloid clearance and recent studies have shown that while there are no differences in beta-amyloid production between healthy controls and sporadic AD patients, in the latter beta-amyloid clearance is reduced by 30%. Novel therapeutic approaches targeting beta-amyloid clearance are being tested. A single oral administration of bexarotene, an FDA approved anti-cancer drug, to a mouse model of AD resulted in enhanced clearance of soluble beta-amyloid in an ApoE-dependent manner and a >50% reduction of beta-amyloid plaque area within just 72 hours. In vivo imaging of beta-amyloid pathology by positron emission tomography (PET) is facilitating research into causes, diagnosis and treatment of major dementias, such as Alzheimer’s disease (AD), where beta-amyloid plays a role. This project aims to use brain amyloid imaging NAV4694 PET scans, for the in vivo assessment of the effect of bexarotene treatment on beta-amyloid burden and its relation to cognition in very early AD and mild AD patients.
Interventions
In brief the study is a 30 day bexarotene treatment in very early Alzheimer's Disease (AD) and mild AD patients measuring;
1.brain beta-amyloid burden using NAV4694-PET scans
2.cognition while on treatment and at 3 months post treatment.
Bexarotene is a US Government (FDA) approved anti-cancer drug, used to treat T-cell lymphoma. In Australia, bexarotene is not marketed or TGA approved. Research studies using mice with AD have shown that bexarotene reduces amyloid plaque and improves mental f
In brief the study is a 30 day bexarotene treatment in very early Alzheimer's Disease (AD) and mild AD patients measuring; 1.brain beta-amyloid burden using NAV4694-PET scans 2.cognition while on treatment and at 3 months post treatment. Bexarotene is a US Government (FDA) approved anti-cancer drug, used to treat T-cell lymphoma. In Australia, bexarotene is not marketed or TGA approved. Research studies using mice with AD have shown that bexarotene reduces amyloid plaque and improves mental function. For the study the visit schedule is 8 visits. First visit is a screening visit and then Bexarotene is dispensed at the following baseline visit (one oral tablet of 150mg/m2 per day for 30 days). Whilst on the study drug there are 4 weekly visits then 2 follow-up visits; at 1 week and 3 months after treatment has ceased. Safety blood tests and cognition tests are performed at these visits and in total two PET scans. Participants will maintain a simple diary to indicate when the dose was taken and if there are any changes to other prescribed medications or condition. The diary is reviewed at each visit.
Sponsors
Nuclear Medicine and Centre for PET Research Fund
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Completion of the standard evaluation and fulfillment of the specific diagnostic criteria for very early Alzheimer's Disaease and mild Alzheimer's Disease. Also to be fluent in English; Age >50; >7 years of education; adequate visual and auditory acuity to complete neuropsychological testing;to have a reliable caregiver who is able to provide accurate information about the patient’s symptoms;
Exclusion criteria
A negative brain PET scan;a lifetime history of schizophrenia, schizoaffective disorder, or treatment with ECT;recent history of drug or alcohol abuse/dependence; any significant disease or unstable medical condition that in the opinion of the investigators, could affect drug levels or neuropsychological testing.
Outcome results
None listed