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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]

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

Alzheimer's Disease with Cerebrovascular Disease

Condition category

Condition code

Alternative and Complementary Medicine

Herbal remedies

Neurological

Dementias

Neurological

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]

Treatment: Other

Comparator / control treatment

Placebo, virtually identical starch capsule containing inactive ingredients

Control group

Placebo

Outcomes

Primary outcome [1]

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]

Baseline, 26 and 52 weeks

Primary outcome [2]

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]

Baseline, 26 and 52 weeks

Secondary outcome [1]

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]

Baseline, 26 and 52 weeks

Secondary outcome [2]

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]

Baseline, 26 and 52 weeks

Secondary outcome [3]

The difference between SLT and the placebo group in the changes between the Cornell Scale of Depression in Dementia scores from Baseline

Timepoint [3]

Baseline, 26 and 52 weeks

Secondary outcome [4]

The difference between SLT and the placebo group in the changes in the dementia quality of life (DEMQOL) scores from baseline

Timepoint [4]

Baseline, 26 and 52 weeks

Secondary outcome [5]

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]

Baseline, 26 and 52 weeks

Secondary outcome [6]

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]

Baseline, 26 and 52 weeks

Secondary outcome [7]

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]

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?

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]

Liverpool Hospital - Liverpool

Recruitment hospital [2]

Bankstown-Lidcombe Hospital - Bankstown

Recruitment hospital [3]

Hornsby Ku-ring-gai Hospital - Hornsby

Recruitment hospital [4]

Wollongong Hospital - Wollongong

Recruitment hospital [5]

The Prince Charles Hospital - Chermside

Recruitment hospital [6]

Norwest Private Hospital - Bella Vista

Recruitment hospital [7]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [8]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [9]

The Queen Elizabeth Hospital - Woodville

Recruitment postcode(s) [1]

2170 - Liverpool

Recruitment postcode(s) [2]

2200 - Bankstown

Recruitment postcode(s) [3]

2077 - Hornsby

Recruitment postcode(s) [4]

2500 - Wollongong

Recruitment postcode(s) [5]

4064 - Milton

Recruitment postcode(s) [6]

2153 - Bella Vista

Recruitment postcode(s) [7]

4032 - Chermside

Recruitment postcode(s) [8]

3050 - Parkville

Recruitment postcode(s) [9]

5000 - Adelaide

Recruitment postcode(s) [10]

5011 - Woodville

Recruitment postcode(s) [11]

2480 - Lismore

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Australia Shineway Technology Pty Ltd

Address [1]

Unit 2806, 591-597 George St,
Sydney NSW 2000

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South Western Sydney Local Health District Human Research Ethics Comittee

Ethics committee address [1]

Locked Bag 7103
Liverpool BC NSW 2170

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

24/02/2014

Approval date [1]

17/11/2014

Ethics approval number [1]

HREC/14/LPOOL/81

Ethics committee name [2]

Western Sydney University Human Research Ethics Comittee

Ethics committee address [2]

Research Engagement, Development and Innovation (REDI)
Locked Bag 1797
Penrith NSW 2751

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

01/09/2016

Approval date [2]

01/09/2016

Ethics approval number [2]

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

A/Prof Dennis Chang

Address

National Institute of Complementary Medicine (NICM), Building J, Western Sydney University
Westmead Campus, 158-160 Hawkesbury Rd, Westmead, NSW 2145

Country

Australia

Phone

+61 2 4620 3310

Fax

+61 2 4620 3722

D.Chang@westernsydney.edu.au

Contact person for public queries

Name

Diana Karamacoska

Address

National Institute of Complementary Medicine (NICM), Building J, Western Sydney University
Westmead Campus, 158-160 Hawkesbury Rd, Westmead, NSW 2145

Country

Australia

Phone

+61 479150816

Fax

+61 2 4620 3291

dementiatrial@westernsydney.edu.au

Contact person for scientific queries

Name

Dennis Chang

Address

National Institute of Complementary Medicine (NICM), Building J, Western Sydney University
Westmead Campus, 158-160 Hawkesbury Rd, Westmead, NSW 2145

Country

Australia

Phone

+61 2 4620 33100

Fax

+61 2 4620 3722

D.Chang@westernsydney.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Source	Title	Year of Publication	DOI
Embase	Study protocol for a phase III randomised controlled trial of Sailuotong (SLT) for vascular dementia and Alzheimer's disease with cerebrovascular disease.	2023	https://dx.doi.org/10.1371/journal.pone.0265285

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically