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Trial registered on ANZCTR


Registration number
ACTRN12620000506998
Ethics application status
Approved
Date submitted
23/03/2020
Date registered
23/04/2020
Date last updated
23/04/2020
Date data sharing statement initially provided
23/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II randomised, double-blind, placebo-controlled trial of S-Adenosyl Methionine (SAMe) in participants with mild cognitive impairment or dementia due to Alzheimer’s disease
Scientific title
A Phase II randomised, double-blind, placebo-controlled trial of S-Adenosyl Methionine on cerebrospinal fluid levels of p-tau in participants with mild cognitive impairment or dementia due to Alzheimer’s disease
Secondary ID [1] 300840 0
N/A
Universal Trial Number (UTN)
U1111-1250-0482
Trial acronym
SAMe
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's disease 316728 0
Mild Cognitive Impairment 316729 0
Condition category
Condition code
Neurological 314974 314974 0 0
Alzheimer's disease
Mental Health 315040 315040 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
400mg S-adenosyl methionine, oral capsules, once daily for 6 months. Drug accountability will be monitored to ensure compliance at every visit.
Intervention code [1] 317167 0
Treatment: Drugs
Comparator / control treatment
Matched Placebo, oral microcrystalline cellulose (MCC) capsules, once daily for 6 months.
Control group
Placebo

Outcomes
Primary outcome [1] 323284 0
Cerebrospinal fluid levels of p-tau assessed via lumbar puncture (spinal tap).
Timepoint [1] 323284 0
Screening and six months (primary endpoint).
Secondary outcome [1] 381432 0
Cognitive function assessment by ADAS-Cog 13.
Timepoint [1] 381432 0
Screening, 3 months, and six months (secondary endpoint).
Secondary outcome [2] 381433 0
Epigenetic changes in DNA methylation.
Timepoint [2] 381433 0
Screening and six months (secondary endpoint).
Secondary outcome [3] 381434 0
Safety assessment via the presence or absence of AE's and SAE's, assessed via participant or study partner self-report, physical examination, vital sign measurement and clinical safety blood testing at all visits.

Known/possible adverse events of SAMe drug may include agitation, anxiety, irritation, and restlessness and the potential to trigger bipolar episodes. There is also a theoretical risk of serotonin syndrome if combined with anti-depressant medications. As such, the study specifically excludes enrolment of individuals with a history of bipolar affective disorder, recent unstable psychiatric condition, or concurrent antidepressant intake.
Timepoint [3] 381434 0
Screening, Randomisation, 1 month, 3 months, six months, follow up (2 weeks post-treatment).

Eligibility
Key inclusion criteria
1. Male and female participants aged 60 years and above at the time of signing the informed consent.
2. Participants who have mild cognitive impairment or dementia due to Alzheimer’s disease, according to the NIA-AA 2011 criteria.
3. Participants who have a standardised mini-mental state examination (sMMSE) score of 20 or above.
4. If using medications to treat symptoms of AD (e.g. donepezil), doses must be stable for at least 8 weeks prior to screening.
5. CSF profile at screening consistent with a profile of AD as defined by Collins et al.
6. Agreeable to undergo lumbar puncture at screening and 6-months.
7. Living at home or in a community setting (assisted living) without continuous nursing care. Each subject must have a reliable caregiver or study partner who sees them at least 3 times weekly, can oversee the administration of study drug, and is willing and able to participate in all clinic visits and some study procedures. The responsible caregiver/ study partner must provide written informed consent to participate.
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any history of bipolar affective disorder.
2. Any medical condition (other than AD) which may contribute to the participant’s cognitive impairment.
3. Stroke or transient ischaemic attack in the past 1 year.
4. Clinically significant unstable psychiatric condition in the last 6 months.
5. Inability to swallow oral medications.
6. Contraindication to undergoing a lumbar puncture at the discretion of the investigator.
7. Other medical conditions, which in the opinion of the investigator, would limit the participant’s survival to < 6 months.
8. Concurrent use of anti-depressant medication (due to the possibility of serotonin syndrome).
9. Participation in another interventional clinical trial or intake of investigational drug within 4 weeks or 5 half-lives (whichever is longer) of the screening visit.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 305294 0
Charities/Societies/Foundations
Name [1] 305294 0
Alzheimer's Association
Address [1] 305294 0
225 N. Michigan Ave., Fl. 17, Chicago, IL 60601
Country [1] 305294 0
United States of America
Primary sponsor type
University
Name
The University of Melbourne
Address
The University of Melbourne
Victoria 3010
Country
Australia
Secondary sponsor category [1] 305654 0
Other Collaborative groups
Name [1] 305654 0
The Walter and Eliza Hall Institute of Medical Research
Address [1] 305654 0
1G, Royal Parade, Parkville
Victoria 3052
Country [1] 305654 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305632 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 305632 0
Level 2
South West
300 Grattan Street, Parkville
Victoria 3010
Ethics committee country [1] 305632 0
Australia
Date submitted for ethics approval [1] 305632 0
Approval date [1] 305632 0
21/06/2019
Ethics approval number [1] 305632 0

Summary
Brief summary
Despite advances in the understanding of the underlying mechanisms of Alzheimer’s disease (AD) the commonest form of dementia, no effective disease modifying therapy exists to date. Plaques containing Amyloid-ß (Aß) and neurofibrillary tangles consisting of hyperphosphorylated tau are the core pathological hallmarks of AD. Widespread predominantly non-prescription use of S-adenosyl methionine (SAMe) currently occurs mainly for depression, osteoarthritis and liver disease. Given its critical role in tau homeostasis, a unique opportunity exists to examine the efficacy and safety of SAMe in a clinical trial of patients with Alzheimer’s disease. It is hypothesised that after six months of treatment with 400mg of oral SAMe, participants with mild cognitive impairment or mild AD will show reduced levels of tau in their cerebrospinal fluid.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101026 0
A/Prof Nawaf Yassi
Address 101026 0
Watson/Yassi Lab
Department of Population Health and Immunity
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade, Parkville VIC 3052 Australia
Country 101026 0
Australia
Phone 101026 0
+61 3 9342 4422
Fax 101026 0
Email 101026 0
yassi.n@wehi.edu.au
Contact person for public queries
Name 101027 0
Ms Jacqui Hayem
Address 101027 0
Watson/Yassi Lab
Department of Population Health and Immunity
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade, Parkville VIC 3052 Australia
Country 101027 0
Australia
Phone 101027 0
+61 0421603488
Fax 101027 0
Email 101027 0
hayem.j@wehi.edu.au
Contact person for scientific queries
Name 101028 0
A/Prof Nawaf Yassi
Address 101028 0
Watson/Yassi Lab
Department of Population Health and Immunity
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade, Parkville VIC 3052 Australia
Country 101028 0
Australia
Phone 101028 0
+61 3 9342 4422
Fax 101028 0
Email 101028 0
yassi.n@wehi.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
No comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results