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Trial registered on ANZCTR


Registration number
ACTRN12617000371392
Ethics application status
Approved
Date submitted
8/03/2017
Date registered
10/03/2017
Date last updated
11/08/2023
Date data sharing statement initially provided
26/03/2019
Date results information initially provided
16/07/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Sailuotong (SLT): A standardised herbal medicine formula for cognitive function in people with mild cognitive impairment
Scientific title
A randomised, double-blind, placebo-controlled 12 week trial of Sailuotong (SLT) for cognitive function in people with mild cognitive impairment
Secondary ID [1] 291348 0
NIL
Universal Trial Number (UTN)
U1111-1193-7674
Trial acronym
MCISLT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild cognitive impairment 302330 0
Condition category
Condition code
Neurological 301915 301915 0 0
Other neurological disorders
Alternative and Complementary Medicine 301916 301916 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
12 weeks 180 mg/day (2 x 45 mg oral capsules each morning and night) SLT formula (81.84 mg ginsenosides, 81.84 mg total ginkgo flavone-glycosides, 16.36 mg crocins).

Each SLT capsule contains a 45 mg standardised mixture of 20.46 mg ginsenosides extracted from Panax ginseng, 20.46 mg total ginkgo flavone-glycosides extracted from Ginkgo biloba, and 4.09 mg crocins extracted from Crocus sativa.

Adherence will be assessed via medication diaries, and collecting any unused tablets and midpoint and endpoint.
Intervention code [1] 297377 0
Treatment: Drugs
Comparator / control treatment
12 weeks 180 mg/day (2 x 45 mg oral capsules each morning and night) starch placebo containing inert substances matched for the colour, taste, and smell of SLT.
Control group
Placebo

Outcomes
Primary outcome [1] 301346 0
Change in Logical Memory Story A - Delayed Recall score
Timepoint [1] 301346 0
Assessed at baseline (week 0) and endpoint (week 12)
Primary outcome [2] 301348 0
Change in D-KEFS Trail Making Test Condition 4 score
Timepoint [2] 301348 0
Assessed at baseline (week 0) and endpoint (week 12)
Primary outcome [3] 301349 0
Change in Digit Symbol Coding score
Timepoint [3] 301349 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [1] 332375 0
Change in Block Design score
Timepoint [1] 332375 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [2] 332376 0
Change in Digit Span score
Timepoint [2] 332376 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [3] 332569 0
Change in D-KEFS Trail Making Test Condition 2 score
Timepoint [3] 332569 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [4] 332570 0
Change in Rey Auditory Verbal Learning Test (RAVLT) score
Timepoint [4] 332570 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [5] 332571 0
Change in Rey Complex Figure Test score
Timepoint [5] 332571 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [6] 332572 0
Change in Benton Visual Retention Test score
Timepoint [6] 332572 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [7] 332573 0
Change in 15-item Boston Naming Test score
Timepoint [7] 332573 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [8] 332574 0
Change in Semantic Fluency test score
Timepoint [8] 332574 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [9] 332575 0
Change in Controlled Oral Word Association Test score
Timepoint [9] 332575 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [10] 332577 0
Mechanisms of action of SLT will be assessed using electroencephalograph (EEG) at rest and in response to audio/visual stimuli to index changes in neurophysiological processes
Timepoint [10] 332577 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [11] 332578 0
Mechanisms of action of SLT will be assessed using autonomic measures of skin conductance and electrocardiograph (ECG) at rest and in response to audio/visual stimuli to index changes in psychophysiological processes
Timepoint [11] 332578 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [12] 332579 0
Mechanisms of action of SLT will be assessed via change in serum inflammatory marker concentrations including IL-6, IL-1beta, and TNF-alpha.
Timepoint [12] 332579 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [13] 332580 0
Mechanisms of action of SLT will be assessed via change in cerebral blood flow measured by common carotid artery ultrasound
Timepoint [13] 332580 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [14] 425410 0
Montreal Cognitive Assessment (MoCA)
Timepoint [14] 425410 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [15] 425411 0
Logical Memory Story A - Immediate Recall
Timepoint [15] 425411 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [16] 425412 0
Functional Activities Questionnaire (FAQ)
Timepoint [16] 425412 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [17] 425413 0
Quality of Life in Alzheimer's Disease scale (QoL-AD)
Timepoint [17] 425413 0
Assessed at baseline (week 0) and endpoint (week 12)
Secondary outcome [18] 425414 0
21-item Depression, Anxiety, Stress Scale (DASS-21)
Timepoint [18] 425414 0
Assessed at baseline (week 0) and endpoint (week 12)

Eligibility
Key inclusion criteria
Greater than or equal to 60 years of age
No diagnosis of dementia
Confirmed diagnosis of MCI due to Alzheimer’s disease core clinical criteria according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) working group guidelines (Albert et al., 2011)
No severe depression by scoring less than or equal to 19 on the Geriatric Depression Scale (GDS)
Agreement to take part in the study as evidenced by a personally signed and dated informed consent document

Albert, M.S., et al., The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement, 2011. 7(3): p. 270-9.
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Less than 60 years of age
Diagnosis of psychiatric disorder(s) including: dissociative disorder, obsessive-compulsive disorder, personality disorder, schizophrenia, bipolar disorder
History of drug and alcohol dependence or substance-related disorders
History of seizures
Head trauma with loss of consciousness
Left-handedness measured by scoring less than 0 on the Edinburgh Handedness Inventory
Allergy to at least 1 ingredient of SLT (Ginkgo biloba, Panax ginseng, or Crocus sativus)
Current use of supplements containing Ginkgo biloba, Panax ginseng, or Crocus sativus (8 week washout period required)
History of several renal and hepatic disorders

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)
Allocation will be concealed using batch numbers generated using a unique random number generator in Microsoft Excel by a University staff member external to the research team. A series of 8 batches numbers will be used (4 for each arm), and sent directly to the drug manufacturer. After eligibility is confirmed, participants will then be allocated to the next numbered box of product by a member of the research team.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised random sequence allocation conducted using a unique random number generator in Microsoft Excel by a University staff member external to the research team. A permuted block randomisation strategy will be used with an allocation ratio of 1:1.
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 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
There are no similar studies using SLT for the proposed study duration (12 weeks) in an MCI cohort. Thus, we selected a well-designed study that used the same primary outcome measure and a similar cohort with a 16 week intervention. That study also provided effect sizes at midpoint (8 weeks; Craft et al., 2012) and demonstrated significantly improved delayed story recall on the Logical Memory Story-A subtest of the WMS-IV following 8 weeks of 20 IU insulin: a treatment group × time interaction, p = .02, Cohen’s f = .36.

We utilised this effect size to conduct a simple a priori sample size calculation based on the Logical Memory Story-A subtest of the WMS-IV. To detect an effect size of Cohen’s f = .36, at a = .05 and 80 % power, 63 participants across 2 groups are required. Allowing for a 20% drop out, this means 76 participants (38 per group) are required. This was rounded-up to 80 (40 per arm) to facilitate the permuted block randomisation strategy. This study is also a pilot efficacy study, so a larger sample size to reach a higher degree of statistical power is not required.

Craft, S., et al., Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment. Archives of Neurology, 2012. 69(1): p. 29-38.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/04/2017
Actual
3/04/2017
Date of last participant enrolment
Anticipated
30/08/2019
Actual
25/02/2020
Date of last data collection
Anticipated
30/11/2019
Actual
8/05/2020
Sample size
Target
80
Accrual to date
Final
79
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 295820 0
Government body
Name [1] 295820 0
NHMRC-ARC Dementia Research Development Fellowship (GNT1102532)
Country [1] 295820 0
Australia
Primary sponsor type
University
Name
Western Sydney University
Address
Locked Bag 1797
Penrith NSW 2751
Country
Australia
Secondary sponsor category [1] 294728 0
None
Name [1] 294728 0
Address [1] 294728 0
Country [1] 294728 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297105 0
Western Sydney University Human Research Ethics Committee
Ethics committee address [1] 297105 0
Locked Bag 1797
Penrith NSW 2751
Ethics committee country [1] 297105 0
Australia
Date submitted for ethics approval [1] 297105 0
20/09/2016
Approval date [1] 297105 0
30/11/2016
Ethics approval number [1] 297105 0
H11878

Summary
Brief summary
Mild cognitive impairment (MCI) causes a slight but noticeable decline in cognitive abilities, and is conceptualised as a transitional prodromal stage between healthy ageing and dementia. It is estimated that up to 35 % of Australians aged 70 and older have MCI, and 15 % of those individuals will go on to develop dementia within a year. Currently, there are no treatment options for MCI, and anti-dementia pharmaceuticals are largely ineffective as they act on a single therapeutic target, which does not address the multifaceted pathophysiology of MCI.

The project aims to evaluate the mechanisms of action and test the efficacy and safety of a novel multi-target treatment for MCI due to Alzheimer's disease: Sailuotong (SLT), a standardised herbal medicine formula. SLT capitalises on the multi-system approach of Chinese herbal medicine, containing multiple standardised active components including Panax ginseng, Ginkgo biloba, and Crocus sativus (saffron), and has already shown promise as a potential treatment for vascular dementia.

This project will involve a 12 week randomised, double-blind, placebo-controlled trial of 180 mg/day SLT for cognitive function in people with MCI due to Alzheimer's disease. The co-primary outcome measures are episodic memory as measured by Logical Memory Story A - Delayed Recall, perceptual processing speed as measured by Digit Symbol Coding, and executive function as measured by the D-KEFS (Delis-Kaplan Executive Function System) Trail Making Test Condition 4 and the Rey Complex Figure Test (RCFT).

Secondary outcome measures include: the Montreal Cognitive Assessment (MoCA), Block Design, Digit Span, Logical Memory Story A - Immediate Recall, D-KEFS Trail Making Test Condition 2, Rey Auditory Verbal Learning Test (RAVLT), Benton Visual Retention Test, 15-item Boston Naming Test, Semantic Fluency, the Controlled Oral Word Association Test, the Functional Activities Questionnaire (FAQ), Quality of Life in Alzheimer's Disease scale (QoL-AD), and the 21-item Depression, Anxiety, Stress Scale (DASS-21).

We will also examine the mechanisms of action of SLT in people with MCI by assessing brain activity via electroencephalograph (EEG), autonomic activity via skin conductance and electrocardiograph (ECG), cerebral blood flow via carotid artery ultrasound, and serum inflammatory markers including IL-6, IL-1beta, and TNF-alpha.
Trial website
http://nicm.edu.au/research/clinical_trials/mci_slt_trial_study
Trial related presentations / publications
Public notes
Attachments [1] 1560 1560 0 0
/AnzctrAttachments/372483-H11878 - Human Ethics Approval - Nov 2016.pdf (Ethics approval)

Contacts
Principal investigator
Name 72990 0
A/Prof Genevieve Steiner
Address 72990 0
NICM, Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Country 72990 0
Australia
Phone 72990 0
+61 2 9685 4761
Fax 72990 0
+61 2 9685 4760
Email 72990 0
g.steiner@westernsydney.edu.au
Contact person for public queries
Name 72991 0
A/Prof Genevieve Steiner
Address 72991 0
NICM, Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Country 72991 0
Australia
Phone 72991 0
+61 2 9685 4761
Fax 72991 0
+61 2 9685 4760
Email 72991 0
g.steiner@westernsydney.edu.au
Contact person for scientific queries
Name 72992 0
A/Prof Genevieve Steiner
Address 72992 0
NICM, Western Sydney University
Locked Bag 1797
Penrith NSW 2751
Country 72992 0
Australia
Phone 72992 0
+61 2 9685 4761
Fax 72992 0
+61 2 9685 4760
Email 72992 0
g.steiner@westernsydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The ethics approval for this study involved the presentation and reporting of aggregated de-identified participant data only.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1735Study protocol    372483-(Uploaded-26-03-2019-12-25-25)-Study-related document.pdf


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA randomized, double-blind, placebo-controlled, parallel-group 12-week pilot phase II trial of SaiLuoTong (SLT) for cognitive function in older adults with mild cognitive impairment.2023https://dx.doi.org/10.1002/trc2.12420
EmbaseStudy protocol for a randomised, double-blind, placebo-controlled 12-week pilot phase II trial of Sailuotong (SLT) for cognitive function in older adults with mild cognitive impairment.2018https://dx.doi.org/10.1186/s13063-018-2912-0
N.B. These documents automatically identified may not have been verified by the study sponsor.