Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000367741
Ethics application status
Approved
Date submitted
2/04/2013
Date registered
5/04/2013
Date last updated
29/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
This study will evaluate if an eye examination can identify changes in the structure of the retina which may help in the early detection of Alzheimer’s disease.
Scientific title
A study to evaluate the ability to detect beta-amyloid plaques utilizing a retinal imaging system and curcumin labeling in patients with Alzheimer’s disease (AD), Mild Cognitive Impairment (MCI), and normal controls
Secondary ID [1] 282213 0
NIL
Universal Trial Number (UTN)
U1111-1141-2765
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzhemiers' Disease 288733 0
Condition category
Condition code
Neurological 289089 289089 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
20 gm curcumin will be taken daily
Oral curcumin will begin on the morning of day 1 and dosing will occur once daily for seven consecutive days.


Curcumin is granular in consistency and not water soluble. For palatability, participants will be provided with a choice of pudding or shake in which to mix their daily dose of curcumin. One option will be dairy-free for lactose-intolerant individuals.

Participants will be asked to take an over the counter vitamin E supplement capsules equivalent to 500 IU daily beginning at the baseline visit (1 day prior to commencing curcumin) and continuing through the final day of curcumin dosing.

Participants will be asked to maintain a Dosing Diary Card recording the dates and times of dosing with curcumin and Vitamin E capsules, to assess compliance.
Intervention code [1] 286829 0
Early detection / Screening
Intervention code [2] 286872 0
Diagnosis / Prognosis
Comparator / control treatment
Participants in the comparator groups will include patients with Mild Cognitive Impairment and also health volunteers. All groups will receive the same intervention.
Control group
Active

Outcomes
Primary outcome [1] 289199 0
The objective of this study is to evaluate the ability to detect beta-amyloid plaques utilizing a retinal imaging system and curcumin labeling in patients with Alzheimer’s disease (AD), Mild Cognitive Impairment (MCI) as compared to age matched, healthy controls, to measure number of plaques, plaque area, and distribution in the retina.
Timepoint [1] 289199 0
imaging will be performed at Baseline and on Day 7.
Secondary outcome [1] 302019 0
Association between retinal imaging and brain amyloid imaging
Timepoint [1] 302019 0
at Baseline and Day 7
Secondary outcome [2] 302020 0
Correlation between the retinal amyloid index (RAI) determination of clinical pathology and the true clinical diagnosis
Timepoint [2] 302020 0
Baseline and Day 7
Secondary outcome [3] 302021 0
Presence or absence of beta-amyloid plaques in control subjects
Timepoint [3] 302021 0
At Baseline and Day 7 participants will have retinal imaging to assess for presence or absence of beta-amyloid plaques.
Secondary outcome [4] 302022 0
Presence or absence of beta-amyloid plaques in MCI and AD patients
Timepoint [4] 302022 0
At Baseline and Day 7 participants will have retinal imaging to assess for presence or absence of beta-amyloid plaques.
Secondary outcome [5] 302026 0
Safety will be evaluated by assessing the incidence of adverse events (AEs) and Serious adverse events (SAEs).

Whilst there have been no reported adverse effects with the intake of this supplement in previous reported human studies, the Sponsor of this trial has reported that there is a risk of Diarrhoea from the consumption of Curcumin.
At each visit participants will be asked if they have experienced any adverse events and if so, the details will be documented in the CRF.
Timepoint [5] 302026 0
Baseline, Day 7 and follow up telephone call at Day 40.

Eligibility
Key inclusion criteria
A Diagnosis of Alzheimer’s Disease (AD), Mild Cognitive Impairment (MCI), and healthy controls (HC) as per the 'The Australian Imaging Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing' criteria ( International Psychogeriatrics / Volume 21 / Issue 04 / August 2009, pp 672-687), stratified as follows:
AD – 10 patients (all Pittsburgh compound B positive (PiB+)) with mild to moderate AD - excluding severe AD)
MCI – 10 patients (5 PiB+, 5 PiB-)
HC – 20 patients (10 PiB+, 10 PiB-)

Participant must be able to provide informed consent.

Participant must be able to assign an individual who will help with recording protocol compliance.

Male or Female 'greater than or equal to' 50 years old

Clear ocular media and pupillary dilation to allow for ocular imaging.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients cannot have major cognitive impairment not associated with AD including a past history or magnetic resonance imaging (MRI) evidence of brain damage including significant trauma, stroke, hydrocephalus, lacunar infarcts, seizures, mental retardation or serious neurological disorder

History of alcoholism or drug addiction within the past year

A score of greater than 4 on the Modified Hachinski Ischemia Scale, indicative of cerebrovascular disease

Systemic illness that could influence the patient’s safety and compliance with the protocol e.g., severe hepatic, renal, cardiovascular or metabolic diseases that would significantly increase patient’s risk to participate in protocol

Advanced retinal disease, cataracts or other ocular conditions that may affect clear images of the retina.

Patients with current or previous bile duct obstruction, gallstones, and gastrointestinal disorders (including stomach ulcers and hyperacidity disorders)

Patients who are pregnant or breast feeding

Hostility or refusal to cooperate

Participation in another clinical trial within 30 days prior to the baseline visit (with the exception of the AIBL trial)

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Open study, no randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All participants that meet the eligibility criteria will commence curcumin.

After an initial evaluation of 40 subjects, it is expected that a total of 200 evaluable subjects will be enrolled in the study.
Phase
Phase 2
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. As more than two groups are to be compared, we will apply one-way ANOVA with Bonferroni (or other suitable) post-hoc testing.

The study is a pilot study to obtain data for proof of concept.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
22/04/2013
Actual
15/04/2013
Date of last participant enrolment
Anticipated
14/04/2014
Actual
12/11/2014
Date of last data collection
Anticipated
Actual
24/12/2014
Sample size
Target
200
Accrual to date
Final
210
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 820 0
Hollywood Private Hospital - Nedlands
Recruitment postcode(s) [1] 6638 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 286980 0
Commercial sector/Industry
Name [1] 286980 0
NeuroVision Imaging, LLC
Country [1] 286980 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
McCusker Alzheimer's Research Foundation
Address
Hollywood Medical Centre
85 Monash Ave
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 285769 0
None
Name [1] 285769 0
Address [1] 285769 0
Country [1] 285769 0
Other collaborator category [1] 277341 0
Other Collaborative groups
Name [1] 277341 0
CSIRO
Address [1] 277341 0
Business Development Manager
Neurodegenerative Diseases, Preventative Health Flagship
343 Royal Parade,
Parkville
VIC 3052
Country [1] 277341 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289030 0
Hollywood Private Hospital Research Ethics Committee
Ethics committee address [1] 289030 0
Monash Ave
NEDLANDS
Locked Bag 2002
WA 6909
Ethics committee country [1] 289030 0
Australia
Date submitted for ethics approval [1] 289030 0
02/10/2012
Approval date [1] 289030 0
05/03/2013
Ethics approval number [1] 289030 0
HPH347

Summary
Brief summary
This study will evaluate whether a simple eye test could detect Alzheimer’s disease earlier than current techniques. We have already found some changes to the blood vessels in the retina, at the back of the eye, in Alzheimer’s disease. This new study will investigate if amyloid plaques, the hallmark of Alzheimer’s disease in the brain, also occur in the retina. A specialised eye camera will be used to take photographs of the retina. In order to highlight amyloid plaques in these photographs, participants will be asked to take a pudding containing Curcumin once per day for 7 days. Curcumin, the main ingredient of the common food spice turmeric, has been reported to have many beneficial health effects, and is being tested in other trials for possible therapeutic benefit in Alzheimer’s disease. Curcumin also has molecular and optical properties that may enable us to image amyloid plaques and hence detect Alzheimer’s disease earlier. It is hoped that this technique could allow us to detect Alzheimer’s disease before the cognitive signs become apparent, hence participants with normal cognition as well as those with memory problems and diagnosed Alzheimer’s disease will be recruited for this study.
Trial website
Trial related presentations / publications
None
Public notes

Contacts
Principal investigator
Name 38854 0
Prof Ralph Martins
Address 38854 0
Sir James McCusker Alzheimer’s Disease Research Laboratory;
Edith Cowan University; and
McCusker Alzheimer’s Research Foundation,
Unit 2, 142 Stirling Highway
Nedlands, WA 6009.
Country 38854 0
Australia
Phone 38854 0
+61893474201
Fax 38854 0
Email 38854 0
[email protected]
Contact person for public queries
Name 38855 0
Kevin Taddei
Address 38855 0
Sir James McCusker Alzheimer’s Disease Research Laboratory;
Edith Cowan University; and
McCusker Alzheimer’s Research Foundation,
Unit 2, 142 Stirling Highway
Nedlands, WA 6009.
Country 38855 0
Australia
Phone 38855 0
+61893474201
Fax 38855 0
Email 38855 0
[email protected]
Contact person for scientific queries
Name 38856 0
Kevin Taddei
Address 38856 0
Sir James McCusker Alzheimer’s Disease Research Laboratory;
Edith Cowan University; and
McCusker Alzheimer’s Research Foundation,
Unit 2, 142 Stirling Highway
Nedlands, WA 6009.
Country 38856 0
Australia
Phone 38856 0
+61893474201
Fax 38856 0
Email 38856 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
SourceTitleYear of PublicationDOI
Dimensions AIExamining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease2015https://doi.org/10.1017/s0007114515004687
EmbaseEmerging ocular biomarkers of Alzheimer disease.2017https://dx.doi.org/10.1111/ceo.12872
N.B. These documents automatically identified may not have been verified by the study sponsor.