Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001679471
Ethics application status
Approved
Date submitted
8/11/2016
Date registered
6/12/2016
Date last updated
3/12/2020
Date data sharing statement initially provided
3/12/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A cross-sectional study to evaluate the ability to detect retinal amyloid-beta plaques utilizing the EidonTM (RetiaTM) retinal imaging system with and without curcumin labeling in participants with Mild Cognitive Impairment (MCI), and healthy controls
Scientific title
A Cross-Sectional study to explore the correlation between PET SUVR and amyloid-beta plaques in the retina, identified by fluorescence imaging using the EidonTM (RetiaTM) retinal imaging system with and without curcumin labeling.
Secondary ID [1] 289906 0
NVI0007
Universal Trial Number (UTN)
Trial acronym
Linked study record
The AIBL study is an observational study and is not registered. A list of publications resulting from this study may be found at the following web site address: https://aibl.csiro.au/publications/

Health condition
Health condition(s) or problem(s) studied:
Mild cognitive impairment 299868 0
Condition category
Condition code
Neurological 299773 299773 0 0
Dementias
Neurological 300916 300916 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. Tropicamide (0.5ml at 1%w/v), eye drops will be administered to each eye on Day 0 (visit one) and visit two of the study (day 3 of dosing). One drop in each eye is administered by the study staff/doctors). Tropicamide is a mydriatic agent that induces dilation of the pupil to facilitate taking images of the retina.

2. Vitamin E oral supplement equal to 500 IU daily in a tablet form to be taken for 3 days coinciding with the dosing of Longvida., It is administered in this study to improve the bioavailability of curcumin from the Longvida supplement. The empty bottle of Vitamin E or any used tablets will be returned to the study site at the second study visit.

3. Curcumin will be supplied in the form of Longvida (Registered Trademark) a formulation designed to improve uptake of curcumin into the body. Each Longvida packet is 20 grams and contains 4 grams of curcumin. Participants are required to take one packet each day for 3 days. Longvida curcumin is granular in consistency and not water soluble. For palatability, participants will be provided with a choice of non-dairy low-lactose shake in which to mix their daily dose of Longvida curcumin. One option will be a special formulated shake for people with diabetes. Longvida (Registered Trademark) is considered an investigational or experimental product. Participants will be advised when to start the Longvida.. For some participants this will be the day after visit 1, for others, it will be at another time point as advised by the study staff to ensure 3 consecutive days of dosing prior to second imaging session. The empty or any unused packets of Lonvida will need to be returned to the study staff at the second visit.

Imaging of the retinas will be done at the screening visit (Visit 1) and at the Day 3 visit (Visit 2) after Curcumin and Vitamin E dosing. The participant’s pupils will be dilated with eye drops prior to each imaging session. Photos will then be taken of the participants’ pupils by a trained operator using the retinal imaging camera RetisTM.
Intervention code [1] 295588 0
Early detection / Screening
Comparator / control treatment
The objective of this study is to explore the correlation between amyloid-beta plaques identified by fluorescence in the retina with PET SUVR and/or CSF amyloid-beta 42 testing in participants at risk for Alzheimer’s dementia previously enrolled in the AIBL Study. The AIBL study participants will be invited into the study. The AIBL study is an observational study and is unregistered. These participants have been classified as
1. "healthy controls" or
2. having mild cognitive impairment.
The data from this study (retinal images) will be compared with the participants' de-identified PET and CSF data.

PET-SUVR is gold-standard biomarker for detection of prodromal Alzheimer's Disease (AD). PET will be utilised to stratify participants into prodromal AD and control groups, for group comparison with respect to retinal plaques and also ROC analysis. PET-SUVR will also be utilised as a continuous parameter to compare brain and retinal plaque burden measures.
CSF (AB42/tau) is an alternative gold-standard biomarker for detection of prodromal AD. CSF will be utilised to stratify participants into prodromal AD and control groups, for group comparison with respect to retinal plaques and also ROC analysis. CSF will also be utilised as a continuous parameter to perform regression analysis between CSF concentrations and retinal plaque burden measures.
RetiaTM (with curcumin) is being used to identify amyloid-beta plaques in the retina. The retina has endogenous fluorophores which will be present in the day0 RetiaTM imaging (without curcumin). Curcumin dosing will allow curcumin to bind to amyloid-beta plaques, producing increased fluorescence. Comparison between pre-dosing and post-dosing RetiaTM imaging is therefore required to detect increased fluorescence due to curcumin binding. Images taken prior to dosing will be compared to those taken after dosing
PET imaging and CSF samples have been collected in the AIBL study (an observational study). The time frame of sample collection was between January 2014 to December 2016.
Control group
Historical

Outcomes
Primary outcome [1] 299300 0
The objective of this study is to explore the correlation between amyloid-beta (AB) plaques identified by fluorescence in the retina with PET SUVR and/or CSF AB42 testing in participants at risk for Alzheimer’s dementia previously enrolled in the AIBL Study.

The primary outcome measure will be the retinal images obtained at day 0 (visit 1) and day 3 of dosing (visit 2) (RetiaTM images)
Timepoint [1] 299300 0
Visit 1 and Visit 2 (day 3 of dosing)
Secondary outcome [1] 326783 0
Safety outcomes will be evaluated by measuring:
a) the incidence of adverse events
b) the incidence of serious adverse events

Assessment will be based on participant reports, either at the study visits or other contact with the site (eg phone call).

Common side effects (1% to 10% chance of occurring) from taking curcumin include
Diarrhoea
Nausea
Bloated feeling
Reflux
Anorexia

Participants may experience slight stinging and reddening of the eyes when the Tropicamide eyedrops are instilled. These are temporary side effects usually lasting less than 5 minutes.
Other very common side effects (greater than 10% chance of occurring) from eye drops may include
Intolerance to bright light.
Blurred vision

Timepoint [1] 326783 0
Adverse events will be tracked until the final follow up safety phone call (30-35 days after visit 2).

Eligibility
Key inclusion criteria
1. Enrolled in the AIBL study with a A Ddiagnosis of MCI, or healthy controls within 36 months as per the AIBL criteria at the screening visit .
2. PET amyloid brain scan within 36 months of baseline visit
3. Participant must be able to provide written informed consent in English.
4. Male or Female age 60 years or older at the screening visit
5. In the opinion of the retinal photographer, clear ocular media and pupillary dilation to allow for ocular imaging
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
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) .
12. In the opinion of the investigator, the participant’s cognitive function is no longer consistent with the AIBL diagnosis.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/01/2017
Actual
27/01/2017
Date of last participant enrolment
Anticipated
Actual
13/08/2019
Date of last data collection
Anticipated
31/12/2018
Actual
13/08/2019
Sample size
Target
284
Accrual to date
Final
286
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 7263 0
Australian Alzheimer’s Research Foundation - Nedlands
Recruitment postcode(s) [1] 14566 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 294317 0
Commercial sector/Industry
Name [1] 294317 0
NeuroVision Imaging, LLC
Country [1] 294317 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
NeuroVision Imaging LLC
Address
NeuroVision Imaging, LLC
1395 Garden Highway
Suite 250
Sacramento, CA 95833
Country
United States of America
Secondary sponsor category [1] 293156 0
Charities/Societies/Foundations
Name [1] 293156 0
Australian Alzheimer's Research Foundation
Address [1] 293156 0
Australian Alzheimer Research Foundation
Hollywood Hospital Consulting Suites,
85 Monash Avenue,
Nedlands, WA, 6009.
Country [1] 293156 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295741 0
Bellberry
Ethics committee address [1] 295741 0
Ethics committee country [1] 295741 0
Australia
Date submitted for ethics approval [1] 295741 0
13/12/2016
Approval date [1] 295741 0
08/11/2016
Ethics approval number [1] 295741 0
2016-09-685

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

Contacts
Principal investigator
Name 68166 0
Prof Roger Clarnette
Address 68166 0
McCusker Alzheimer Research Foundation
Unit 2 / 142 Stirling Highway
Nedlands, WA, 6009
Country 68166 0
Australia
Phone 68166 0
+61 8 6304 3966
Fax 68166 0
+61 8 6389 2033
Email 68166 0
[email protected]
Contact person for public queries
Name 68167 0
Shaun Frost
Address 68167 0
C/-CSIRO
Private Bag 5
WEMBLEY WA 6913
Country 68167 0
Australia
Phone 68167 0
+61 8 9333 6137
Fax 68167 0
not available
Email 68167 0
[email protected]
Contact person for scientific queries
Name 68168 0
Shaun Frost
Address 68168 0
C/-CSIRO
Private Bag 5
WEMBLEY WA 6913
Country 68168 0
Australia
Phone 68168 0
+61 8 9333 6137
Fax 68168 0
none
Email 68168 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.