ANZCTR - Registration

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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

19/08/2022

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 (SAMe) in participants with mild cognitive impairment or dementia due to Alzheimer’s disease

Secondary ID [1]

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

Mild Cognitive Impairment

Condition category

Condition code

Neurological

Alzheimer's disease

Mental Health

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]

Treatment: Drugs

Comparator / control treatment

Matched Placebo, oral microcrystalline cellulose (MCC) capsules, once daily for 6 months.

Control group

Placebo

Outcomes

Primary outcome [1]

Plasma levels of p-tau181

Timepoint [1]

Screening and six months (primary endpoint).

Secondary outcome [1]

Cognitive function assessment by RBANS,

Timepoint [1]

Screening and six months (secondary endpoint).

Secondary outcome [2]

Epigenetic changes in DNA methylation.

Timepoint [2]

Screening and six months (secondary endpoint).

Secondary outcome [3]

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]

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 18 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. 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

Sex

Both males and females

Can healthy volunteers participate?

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. Other medical conditions, which in the opinion of the investigator, would limit the participant’s survival to < 6 months.
7. Concurrent use of anti-depressant medication (due to the possibility of serotonin syndrome).
8. 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

Recruiting

Date of first participant enrolment

Anticipated

1/03/2021

Actual

16/04/2021

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

Recruitment hospital [1]

Austin Health - Heidelberg Repatriation Hospital - Heidelberg West

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

3081 - Heidelberg West

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Alzheimer's Association

Address [1]

225 N. Michigan Ave., Fl. 17, Chicago, IL 60601

Country [1]

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]

Other Collaborative groups

Name [1]

The Walter and Eliza Hall Institute of Medical Research

Address [1]

1G, Royal Parade, Parkville
Victoria 3052

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health Human Research Ethics Committee

Ethics committee address [1]

Level 2
South West
300 Grattan Street, Parkville 
Victoria 3010

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

21/06/2019

Ethics approval number [1]

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 p-tau181 in their plasma.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Nawaf Yassi

Address

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

Australia

Phone

+61 3 9342 4422

Fax

yassi.n@wehi.edu.au

Contact person for public queries

Name

Alisa Turbic

Address

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

Australia

Phone

+61393452210

Fax

turbic.a@wehi.edu.au

Contact person for scientific queries

Name

Nawaf Yassi

Address

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

Australia

Phone

+61 3 9342 4422

Fax

yassi.n@wehi.edu.au

Data sharing statement

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

No/undecided IPD sharing reason/comment

No 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	Protocol of a Phase II Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial of S-Adenosyl Methionine in Participants with Mild Cognitive Impairment or Dementia Due to Alzheimer's Disease.	2023	https://dx.doi.org/10.14283/jpad.2023.55

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