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Trial registered on ANZCTR


Registration number
ACTRN12616000057482
Ethics application status
Approved
Date submitted
26/10/2015
Date registered
20/01/2016
Date last updated
2/02/2022
Date data sharing statement initially provided
30/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical trial of Sailuotong (SLT) for Vascular Dementia or Alzheimer's Disease with evidence of cerebrovascular disease
Scientific title
A Multicentre, Randomised, Double-Blind, Placebo Controlled Trial to Evaluate the Effectiveness and Safety of Sailuotong (SLT), a Standardised Herbal Medicine Formula in Patients with Vascular Dementia and Alzheimer's Disease with Cerebrovascular Disease
Secondary ID [1] 287651 0
Nil known
Universal Trial Number (UTN)
U1111-1175-5097
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vascular Dementia 296483 0
Alzheimer's Disease with Cerebrovascular Disease 296484 0
Condition category
Condition code
Alternative and Complementary Medicine 296740 296740 0 0
Herbal remedies
Neurological 296854 296854 0 0
Dementias
Neurological 296855 296855 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
STL active compounds: Ginsenosides powder – 27.27 mg per capsule; ginkgo flavone glycosides–27.27 mg per capsule; crocins – 5.46 mg per capsule. Participants randomised to the active group will take 2 SLT capsules (60 mg/capsule) orally, twice daily for 52 weeks. Adherence to the protocol will be monitored by drug tablet return.
Intervention code [1] 293070 0
Treatment: Other
Comparator / control treatment
Placebo, virtually identical starch capsule containing inactive ingredients
Control group
Placebo

Outcomes
Primary outcome [1] 296379 0
The difference between SLT and the placebo groups in the changes between the Vascular Dementia Assessment Scale-cognitive Subscale (VaDAS-cog) scores from baseline
Timepoint [1] 296379 0
Baseline, 26 and 52 weeks
Primary outcome [2] 296462 0
The difference between SLT and the placebo groups in the changes between the Alzheimer's Disease Cooperative Study-activities of daily living (ADCS-ADL) scores from baseline
Timepoint [2] 296462 0
Baseline, 26 and 52 weeks
Secondary outcome [1] 318294 0
The difference between SLT and the placebo group in the changes between the Clinician’s Interview Based Impression of Change-plus (CIBIC-plus) scores from baseline
Timepoint [1] 318294 0
Baseline, 26 and 52 weeks
Secondary outcome [2] 318295 0
The differences between the SLT and placebo group in the changes between the additional executive function tests including CLOX and EXIT-25 scores from baseline
Timepoint [2] 318295 0
Baseline, 26 and 52 weeks
Secondary outcome [3] 318296 0
The difference between SLT and the placebo group in the changes between the Cornell Scale of Depression in Dementia scores from Baseline
Timepoint [3] 318296 0
Baseline, 26 and 52 weeks
Secondary outcome [4] 318297 0
The difference between SLT and the placebo group in the changes in the dementia quality of life (DEMQOL) scores from baseline
Timepoint [4] 318297 0
Baseline, 26 and 52 weeks
Secondary outcome [5] 318298 0
The difference between SLT and the placebo groups in the changes in neuropsychiatric symptoms (comprising delusions, hallucinations, depression/dysphoria, anxiety, agitation/aggression, euphoria, dis-inhibition, irritability/lability, apathy, aberrant motor activity and, night-time behaviour disturbances) in the changes in the Neuropsychiatric Inventory-Clinician rating scale (NPI-C) scores from Baseline.
Timepoint [5] 318298 0
Baseline, 26 and 52 weeks
Secondary outcome [6] 318299 0
The difference between SLT and the placebo groups in the changes between changes in cerebral blood flow and volumes as determined by MRI from Baseline
Timepoint [6] 318299 0
Baseline, 26 and 52 weeks
Secondary outcome [7] 318504 0
Safety - 'Liver and renal function and routine haematological tests (FBC, coagulation, platelet function) will be conducted at each visit and any AEs will be reported. Although serious adverse events (SAEs) are not anticipated for this trial, SAE procedures will be followed in these circumstances.
Timepoint [7] 318504 0
Baseline, week 4, 13, 26,30, 52

Eligibility
Key inclusion criteria
1. 40-85* years old;
2. Outpatients diagnosed with either probable VaD as defined by the National Institute of 3. Neurological Disorders and Stroke (NINCDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) or possible Alzheimer’s Disease as defined by the National Institute of Neurological and Communication Disorders and Stroke (NINCDS)-Alzheimer's Disease and Related Disorders Association (ADRDA) with significant neuroimaging (CT or MRI) evidence of cerebrovascular disease;
3.. An MMSE score between 10 - 24 for the diagnosis of mild to moderate dementia;
4. Absence of severe depression (Geriatric Depression Scale 15-item version, total score <=11);
5. Stable or controlled by optimal medication over at least 3 months for, (if present) hypertension, diabetes, cardiac disease or stroke, or if on hypnotics and sedatives
6. Agreement to take part in the study as evidenced by a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative if the subject is unable to provide consent), has been informed of all pertinent aspects of the study;
7. Participants must also have a Study Partner/Carer, that can assist the subject comply with the study protocol. This requires the Study Partner/Carer to be in contact with the subject at least 2 days per week;
8. If female, has no intention to become pregnant during the study.
Minimum age
40 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have other types of dementia, and/or severe form of delirium, depression, schizophrenia, acute illness or poorly controlled chronic diseases
2. If receiving any of the following drugs: donepezil, rivastigmine, galantamine, memantine, huperzine, have been on a stable dose for six months
3. Have a history of severe forms of peptic ulcers, diabetes with complications, pulmonary disorders, renal and/or hepatic disorders
4. Abnormal pathology test results: Cr > 1.5 times upper limit of normal (ULN); Alt, AST or ALP > 2 times ULN; PT > 3 second more than ULN; APTT > 10 seconds more than ULN; Plt < 100,000/mcL
5. Have severe dysphasia, mental retardation and/or life expectancy < 6 months
6. Are allergic to more than 2 medications or at least 1 ingredient of SLT
7. Are pregnant or lactating women
8. Currently consuming any ingredients in the SLT formula including ginseng, ginkgo and saffron,
9. Are participating in another clinical trial
10. Have a stroke in the 3 months before screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A statistician external to the research team generated the randomisation treatment sequence using block randomisation to evenly allocate participants into either the active or placebo treatment group. Allocation concealment - the principal investigator will determine the eligibility of each subject who will then, if eligible, be allocated to the next numbered box of product by the clinical research nurse or research associate.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The method of sequence generation was done using a freely available online computer application randomization.com by a statistician external to the research team
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Based on the magnitude of ADAS-cog improvement in previous trials using ginkgo for dementia, an improvement of ADAS-cog of at least 2 points (with a standard deviation of 3.9 units) was used to calculate sample size. As a result, a total of 162 patients are required to detect this difference with 90% power at the 0.05 significance level. A sample of 170 will be needed to give 90% power to detect a 4-point change in ADCS-ADL with an estimated standard deviation of 8.0. Allowing for a total non-compliance/withdrawal rate of 25%, 226 participants will be recruited into the trial across all centres to ensure 170 patients in the final analyses.

Data will be analysed using linear mixed models through which we will test for differences between treatment group on each outcome over time, with adjustment for random variation between treatment centres, with and without adjustment for other potentially important predicts (e.g. compliance, age, gender, severity of VaD). Non-linear changes over time by a) fitting time as categorical variable and b) testing for quadratic and cubic effects will be tested for. Results will be reported as regression coefficients (or odds ratios if categorical) and associated 95% confidence intervals.

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
1/02/2016
Actual
1/08/2016
Date of last participant enrolment
Anticipated
31/12/2021
Actual
19/02/2021
Date of last data collection
Anticipated
1/12/2021
Actual
Sample size
Target
250
Accrual to date
149
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 4478 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 4479 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [3] 4480 0
Hornsby Ku-ring-gai Hospital - Hornsby
Recruitment hospital [4] 4481 0
Wollongong Hospital - Wollongong
Recruitment hospital [5] 7279 0
The Prince Charles Hospital - Chermside
Recruitment hospital [6] 7280 0
Norwest Private Hospital - Bella Vista
Recruitment hospital [7] 9854 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [8] 14018 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [9] 14019 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 10663 0
2170 - Liverpool
Recruitment postcode(s) [2] 10664 0
2200 - Bankstown
Recruitment postcode(s) [3] 10665 0
2077 - Hornsby
Recruitment postcode(s) [4] 10666 0
2500 - Wollongong
Recruitment postcode(s) [5] 15047 0
4064 - Milton
Recruitment postcode(s) [6] 15048 0
2153 - Bella Vista
Recruitment postcode(s) [7] 15049 0
4032 - Chermside
Recruitment postcode(s) [8] 18638 0
3050 - Parkville
Recruitment postcode(s) [9] 26807 0
5000 - Adelaide
Recruitment postcode(s) [10] 26808 0
5011 - Woodville
Recruitment postcode(s) [11] 33204 0
2480 - Lismore

Funding & Sponsors
Funding source category [1] 292237 0
Commercial sector/Industry
Name [1] 292237 0
Australia Shineway Technology Pty Ltd
Country [1] 292237 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Australia Shineway Technology Pty Ltd
Address
Unit 2806, 591-597 George St,
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 290949 0
None
Name [1] 290949 0
Address [1] 290949 0
Country [1] 290949 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293703 0
South Western Sydney Local Health District Human Research Ethics Comittee
Ethics committee address [1] 293703 0
Locked Bag 7103
Liverpool BC NSW 2170
Ethics committee country [1] 293703 0
Australia
Date submitted for ethics approval [1] 293703 0
24/02/2014
Approval date [1] 293703 0
17/11/2014
Ethics approval number [1] 293703 0
HREC/14/LPOOL/81
Ethics committee name [2] 296661 0
Western Sydney University Human Research Ethics Comittee
Ethics committee address [2] 296661 0
Research Engagement, Development and Innovation (REDI)
Locked Bag 1797
Penrith NSW 2751
Ethics committee country [2] 296661 0
Australia
Date submitted for ethics approval [2] 296661 0
01/09/2016
Approval date [2] 296661 0
01/09/2016
Ethics approval number [2] 296661 0
H11554

Summary
Brief summary
Dementia is the leading cause of mental and physical disability in the elderly. Vascular dementia (VaD) that accounts for 15-20% of all dementia cases is a syndrome of acquired cognitive functional impairment with a complex pathophysiological basis. Viable pharmaceutical options are currently lacking.

Herbal medicine has been used for the treatment of ageing-related disorders for more than 2000 years ago in ancient China. Combination therapies are complex mixtures are believed to be able to enhance therapeutic efficacy through synergistic and multi-target mechanisms and are ideal and may be relevant for disorders such as VaD that has multifactorial / multisystem pathophysiology components. Conventional pharmaceutical techniques have been used to develop a novel, standardised herbal formulation, Sailuotong (SLT) targeting VaD. Data from pre-clinical studies have shown significant improvements in memory functions and in pathogenic biochemical parameters in various animal models. Appropriate safety of SLT has also been shown in acute and chronic toxicity and herb-drug interactions studies.

We propose to undertake a rigorous phase III clinical trial of SLT in 250 patients with mild to moderate probable VaD or Alzheimer’s disease with cerebrovascular disease (AD+CVD). The aim of this 52-week randomised, multicentre, double-blind, placebo controlled trial is to:
1. Determine the efficacy of SLT on cognitive function and activities of daily living, and
2. Monitor the safety of SLT as a treatment for VaD or AD+CVD during a 52-week treatment period.

The primary outcome measures include Vascular Dementia Assessment Scale cognitive subscale (VaDAS-cog) and Alzheimer’s Disease Co-operative Study Activities of Daily Living Inventory (ADCS-ADL). In addition, there are six secondary outcome measures including: The Clinician’s Interview Based Impression of Change-plus (CIBIC-plus), CLOX, EXIT-25, Quality of life, Neuropsychiatric Inventory-Clinician rating scale (NPI-C), and Functional MRI Assessment in a subset group.

Liver and renal function and routine haematological tests will be conducted regularly during the trial. All adverse events will be recorded at each visit, including those suspected to be related to the treatment and any worsening of symptoms will be closely monitored.
Trial website
http://www.nicm.edu.au/nicm/clinical_trials/slt_for_vascular_dementia
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60942 0
A/Prof Dennis Chang
Address 60942 0
National Institute of Complementary Medicine (NICM), Building J, Western Sydney University
Westmead Campus, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country 60942 0
Australia
Phone 60942 0
+61 2 4620 3310
Fax 60942 0
+61 2 4620 3722
Email 60942 0
[email protected]
Contact person for public queries
Name 60943 0
Diana Karamacoska
Address 60943 0
National Institute of Complementary Medicine (NICM), Building J, Western Sydney University
Westmead Campus, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country 60943 0
Australia
Phone 60943 0
+61 479150816
Fax 60943 0
+61 2 4620 3291
Email 60943 0
[email protected]
Contact person for scientific queries
Name 60944 0
Dennis Chang
Address 60944 0
National Institute of Complementary Medicine (NICM), Building J, Western Sydney University
Westmead Campus, 158-160 Hawkesbury Rd, Westmead, NSW 2145
Country 60944 0
Australia
Phone 60944 0
+61 2 4620 33100
Fax 60944 0
+61 2 4620 3722
Email 60944 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
SourceTitleYear of PublicationDOI
EmbaseStudy protocol for a phase III randomised controlled trial of Sailuotong (SLT) for vascular dementia and Alzheimer's disease with cerebrovascular disease.2023https://dx.doi.org/10.1371/journal.pone.0265285
N.B. These documents automatically identified may not have been verified by the study sponsor.