Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000465752
Ethics application status
Not yet submitted
Date submitted
21/04/2013
Date registered
24/04/2013
Date last updated
24/04/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Apolipoprotein E driven therapeutics for Alzheimer’s disease
Scientific title
A study evaluating the effects of Apolipoprotein E driven therapeutics for Alzheimer’s disease
Secondary ID [1] 282373 0
Nil
Universal Trial Number (UTN)
U1111-1141-4103
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 288955 0
Condition category
Condition code
Neurological 289288 289288 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 287005 0
Treatment: Drugs
Comparator / control treatment
NA- This is a single group study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289399 0
Brain ABeta burden as measured by NAV4694-PET scan
Timepoint [1] 289399 0
A baseline scan is taken and then at the completion of 30 days of treatment of bexarotene
Secondary outcome [1] 302397 0
Change in cognition.
Cognition is assessed through neuropsychological assessments where memory and attention tasks are completed. Assessments take 1-2 hours.
Timepoint [1] 302397 0
The assessments will occur at screening, the last week of treatment then at 3 months post treatment.

Eligibility
Key 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;


Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Twenty participants with very early AD or mild Alzheimer’s disease will be recruited from the Austin Health Memory Disorders Clinic and affiliated specialists with expertise in memory disorders.
Very early AD and mild AD is defined for this study as subjective and objective evidence of cognitive decline with a composite episodic memory score more than 1 standard deviation below the age matched norm, minimental state examination (MMSE) score of greater than 22, Clinical Dementia Rating of 0.5 or 1, and a PET scan that is positive for brain amyloid.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
20 participants are needed to achieve study objectives. This is a preliminary, exploratory study to determine if a larger and double blind, placebo controlled trial is warranted.
The hypotheses that bexarotene treatment reduces NAV retention over time will be tested by paired Student’s t-tests
The hypotheses that bexarotene treatment improves cognition will also be tested by paired Student’s t-tests.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/06/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 924 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 6772 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 287143 0
Hospital
Name [1] 287143 0
Nuclear Medicine and Centre for Positron Emission Tomography (PET ) Research Fund
Country [1] 287143 0
Australia
Primary sponsor type
Hospital
Name
Nuclear Medicine and Centre for PET Research Fund
Address
Level 1, Harold Stokes Building
Austin Hospital
Studley Rd
Heidelberg 3084
Country
Australia
Secondary sponsor category [1] 285911 0
None
Name [1] 285911 0
Address [1] 285911 0
Country [1] 285911 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 289142 0
Austin Health, Heidelberg, Human Research Ethics Committee
Ethics committee address [1] 289142 0
Level 6 , Horold Stokes Building
Austin Hospital
studley Rd
Heidelberg, VIC 3084
Ethics committee country [1] 289142 0
Australia
Date submitted for ethics approval [1] 289142 0
01/05/2013
Approval date [1] 289142 0
Ethics approval number [1] 289142 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39458 0
Prof Christopher Rowe
Address 39458 0
Level 1 Harold Stokes Building
Austin Hospital
145 Studley Rd
Heidelberg VIC 3084
Country 39458 0
Australia
Phone 39458 0
+61 3 94965183
Fax 39458 0
Email 39458 0
[email protected]
Contact person for public queries
Name 39459 0
Ms Robyn Veljanovski
Address 39459 0
Level 1 Harold Stokes Building
Austin Hospital
145 Studley Rd
Heidelberg VIC 3084
Country 39459 0
Australia
Phone 39459 0
+61 3 94963579
Fax 39459 0
Email 39459 0
[email protected]
Contact person for scientific queries
Name 39460 0
Prof Christopher Rowe
Address 39460 0
Level 1 Harold Stokes Building
Austin Hospital
145 Studley Rd
Heidelberg VIC 3084
Country 39460 0
Australia
Phone 39460 0
+61 3 94965183
Fax 39460 0
Email 39460 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.