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Trial registered on ANZCTR


Registration number
ACTRN12615000465550
Ethics application status
Approved
Date submitted
8/04/2015
Date registered
13/05/2015
Date last updated
24/09/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Imaging of Retinal Amyloid Plaques in Alzheimer’s disease – Longitudinal Study.
Scientific title
A study to evaluate the ability to detect beta-amyloid plaques and changes in plaque burden over time utilizing a retinal imaging system and curcumin labeling in participants with Mild Cognitive Impairment (MCI), and normal controls
Secondary ID [1] 286434 0
NVI003.A
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 294603 0
Condition category
Condition code
Neurological 294906 294906 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Suitable participants will receive a 7 day course of Curcumin and an 8 day course of over the counter 500 IU of Vitamin E (taken as one capsule once per day). Clinic visits occur on day 0 and day 7. Curcumin dosing is on days 1-7 inclusive. Vitamin E dosing is on days 0-7 inclusive.

Curcumin will be supplied in the form of Longvida (Registered Trademark) sachets Participants will take 20 grams of Longvida (Registered Trademark) each morning before breakfast for 7 days, which is equivalent to 4 grams of Curcumin. The sachets may be mixed with a low-lactose drink (supplied). Longvida (Registered Trademark) is currently not registered for this indication in Australia and is therefore considered an investigational or experimental product.

At each clinic visit, participants will have a blood test and have photos taken of their eye retina's. To take the photos, pupil-dilating eye drops will be instilled into the eyes. Photos will be taken with a scanning laser ophthalmoscope.

In addition, participants are asked to complete a medication diary during the course of the Curcumin/Vitamin E to record all the medication intake. All Curcumin and Vitamin E containers should be returned to the clinic, even if they are empty.
Intervention code [1] 291512 0
Early detection / Screening
Comparator / control treatment
All suitable participants will receive Curcumin and Vitamin E. The results from participants with Mild Cognitive Impairment will be compared to the results from the Healthy Control group. In addition, the results will be correlated with the participant's results from participation in the parent study. Data from the parent study was collected from April 2013 to November 2014. The parent study is known as NVI003 (ACTRN12613000367741)
Control group
Active

Outcomes
Primary outcome [1] 294662 0
The primary endpoint is to evaluate the ability to detect changes over time in retinal beta-amyloid plaque burden, utilizing a retinal imaging system and curcumin labeling in participants.
Timepoint [1] 294662 0
Comparison with results from participation in previous study. Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing)
Primary outcome [2] 294664 0
The second objective is to compare rate of change of retinal beta-amyloid plaque burden with brain beta-amyloid plaque burden in PET+ and PET- participants, including rate of change of brain beta-amyloid plaque burden in participants for which this data is available through the AIBL study.
Timepoint [2] 294664 0
Comparison with results from participation in previous study. Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing)
Secondary outcome [1] 313824 0
Association between the amount of beta-amyloid plaques in the retinal imaging compared to the amount in the brain imaging
Timepoint [1] 313824 0
Comparison with results from participation in previous study. Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing)
Secondary outcome [2] 313826 0
Correlation between the retinal amyloid index (RAI), clinical pathology and the true clinical diagnosis. Clinical pathology will be assessed by blood sample analysis and true clinical diagnosis will be assessed by physician diagnosis.
Timepoint [2] 313826 0
Comparison with results from participation in previous study. Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing)
Secondary outcome [3] 313827 0
Presence or absence of retinal plaques in control subjects as assessed by retinal amyloid fluorescence imaging and automated measurement of retinal amyloid index
Timepoint [3] 313827 0
Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing)
Secondary outcome [4] 313828 0
The effect of other parameters on the retina-brain amyloid association, including ocular history, blood pharmacokinetics, demographics, and APOE genotype. Ocular history and demographic information are collected by interview. Blood curcumin levels and APOE genotype are determined from blood sample analysis.
Timepoint [4] 313828 0
Comparison with results from participation in previous study. Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing). Ocular history and demographic information are collected by interview at day 0. Blood is collected at day 0 and day 7 for measurement of curcumin levels.
Secondary outcome [5] 313829 0
Presence or absence of retinal plaques in MCI participant as assessed by retinal amyloid fluorescence imaging and automated measurement of retinal amyloid index
Timepoint [5] 313829 0
Images from this study will be collected at day 0 (before starting Curcumin) and day 7 (last day of Curcumin dosing)

Eligibility
Key inclusion criteria
1. Participant must have completed curcumin based fluorescence retinal imaging under the NVI003 study (ACTRN12613000367741) within the previous 21 months (please note that the NVI003 study is not the same as the AIBL study but the NVI003 study drew from AIBL data)
2. Participants must be able to provide written informed consent in English.
3. Male or Female age = 50
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The participant has advanced retinal disease, advanced cataracts or other advanced ocular conditions that in the opinion of the investigator are likely to affect obtaining clear images of the retina.
2. Participant has had prior ocular surgery within 2 months of planned retinal imaging, or is still taking post-operative ocular medications at first day of retinal imaging.
3. Participants with known current gallstone.
4. Participants who have undergone angioplasty in the last 3 months.
5. Participants who have had major surgery within 4 weeks of trial inclusion or planned surgical procedure during the trial period.
6. Significant haemorrhagic event (in past 12 months) or cardiovascular disease ( ie, history of myocardial infarction within past 6 months of trial inclusion , congestive cardiac failure NYHA grade II ).
7. Participant with retinitis pigmentosa.
8. Participants with current bile duct obstruction (participants who have undergone a cholecystectomy will be considered eligible).
9. Participants with significant uncontrolled gastrointestinal disorders (including stomach ulcers and uncontrolled hyperacidity disorders) which in the opinion of the investigator will be aggravated by the intake of curcumin.
10. Participants with known allergy to Tropicamide eye drops, vitamin E or turmeric.
11. Participation in another clinical trial within 30 days prior to visit one (with the exception of the AIBL trial). ( Please note that the NVI003 study is not the same as the AIBL study but the NVI003 study drew from AIBL data).

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Open study - not randomised
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
Other
Other design features
Participants will be stratified into 2 cohorts
1. Mild Cognitive Impairment
2. Healthy Controls.
This status will be assigned based on the AIBL criteria and any follow up tests required.
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical analysis applies within retinal sampling/imaging [number, size and location] of beta-amyloid plaques and will be compared between diagnostic groups and across imaging sessions in the same individuals. We will apply one-way ANOVA with Bonferroni (or other suitable) post-hoc testing. A power analysis was performed based on the expected change in retinal amyloid burden and one-way ANOVA testing. 80% power to detect a statistically significant difference in ‘retinal plaque burden change’ between groups requires group sizes of n=20 or above.The target sample size of 100 is expected to include different strata for comparison: MCI n>20, HC n~80,
HC+ n>20, HC- n>20. While recruiting from a limited cohort means we are unable to ensure minimum numbers in each strata, a sample size of 100 should enable comparisons across groups with at least n=20 in each group, which is the number required to detect a significant difference based on the power analysis.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/05/2015
Actual
5/05/2015
Date of last participant enrolment
Anticipated
Actual
8/12/2015
Date of last data collection
Anticipated
Actual
21/01/2016
Sample size
Target
100
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 3720 0
McCusker Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 9399 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 291004 0
Commercial sector/Industry
Name [1] 291004 0
Neuro Vision Inc
Country [1] 291004 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
McCusker Alzheimer's Research Foundation
Address
115 Monash Ave
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 289682 0
Commercial sector/Industry
Name [1] 289682 0
Neuro Vision Inc
Address [1] 289682 0
1395 Garden Highway
Suite 250
Sacramento, CA 95833
Country [1] 289682 0
United States of America
Other collaborator category [1] 278421 0
Government body
Name [1] 278421 0
CSIRO
Address [1] 278421 0
Business Development Manager
Neurodegenerative Diseases, Preventative Health Flagship
343 Royal Parade
PARKVILLE VIC 3052
AUSTRALIA
Country [1] 278421 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292590 0
Hollywood Private Hospital Research Ethics Committee
Ethics committee address [1] 292590 0
Ethics committee country [1] 292590 0
Australia
Date submitted for ethics approval [1] 292590 0
04/03/2015
Approval date [1] 292590 0
01/04/2015
Ethics approval number [1] 292590 0
HPH 407

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 56126 0
Prof Roger Clarnette
Address 56126 0
McCusker Alzheimer's Research Foundation
115 Monash Ave
NEDLANDS WA 6009
Country 56126 0
Australia
Phone 56126 0
+61 8 9389 6433
Fax 56126 0
Email 56126 0
[email protected]
Contact person for public queries
Name 56127 0
Kevin Taddei
Address 56127 0
McCusker Alzheimer's Disease Foundation
2/142 Stirling Highway
NEDLANDS WA 6009
Country 56127 0
Australia
Phone 56127 0
+61 8 6304 3966
Fax 56127 0
Email 56127 0
[email protected]
Contact person for scientific queries
Name 56128 0
Shaun Frost
Address 56128 0
CSIRO DPAS WA
Australian e-Health Research Centre
Private bag 5, Wembley WA 6913 Australia
Country 56128 0
Australia
Phone 56128 0
+61 8 9333 6137
Fax 56128 0
Email 56128 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

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