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Trial registered on ANZCTR


Registration number
ACTRN12621001364864
Ethics application status
Approved
Date submitted
1/09/2021
Date registered
8/10/2021
Date last updated
19/09/2023
Date data sharing statement initially provided
8/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Cannabidiol: Treatment for brain changes and depression in early-stage dementia
Scientific title
Cannabidiol: Treatment for brain changes and depression in early-stage dementia
Secondary ID [1] 305192 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
Not applicable.
Linked study record
Not applicable.

Health condition
Health condition(s) or problem(s) studied:
Early-stage dementia 323468 0
Condition category
Condition code
Neurological 321024 321024 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention of interest is cannabidiol (CBD). For the intervention group, medical grade 99.9% pure CBD will be formulated into capsules for oral administration. Each CBD capsule will contain either 100mg or 200mg CBD powder solved in Softisan 378 gelatin capsules. Participants will take two capsules per day. Participants will commence the trial on a daily dose of 200mg/day for the first two weeks, which involves taking one 100mg capsule in the morning and one 100mg capsule in the evening, with food. If no adverse effects are reported, then the daily dose will be escalated to 300mg/day for the remaining ten weeks of the trial - the evening dose will be increased to 200mg, with the morning dose remaining at 100mg. If an adverse event is reported at 200mg, participants will be discontinued from the trial. Medication adherence will be assessed primarily by blood test to measure CBD concentrations in plasma. A supporting person, nominated by the participant, will further assist with medication adherence by recording when capsules are taken and by returning medication containers each week when new weekly doses are provided.
Intervention code [1] 321596 0
Treatment: Drugs
Comparator / control treatment
The control treatment for the current trial will be administration of placebo. Placebo capsules will be made from gelatin and contain only vehicle (Softisan 378). Placebo capsules will appear identical to the CBD capsules in terms of appearance, flavour and scent.
Participants who take placebo will take one capsule in the morning and one capsule in the evening with food.
Control group
Placebo

Outcomes
Primary outcome [1] 328802 0
Change in brain structure, as measured by MRI scans.
Timepoint [1] 328802 0
12 weeks after intervention commencement.
Primary outcome [2] 328803 0
Change in white matter connectivity, as measured by tractography.
Timepoint [2] 328803 0
12 weeks after intervention commencement.
Primary outcome [3] 328804 0
Change in cognition, as measured by the Cognitive Functional Composite (CFC).
Timepoint [3] 328804 0
6 weeks and 12 weeks (primary timepoint) after intervention commencement.
Secondary outcome [1] 400454 0
Change in cognition, as measured by the Frontal Assessment Battery (FAB). This is a primary outcome.
Timepoint [1] 400454 0
6 weeks and 12 weeks (primary timepoint) after intervention commencement.
Secondary outcome [2] 400455 0
Change in depression, as measured by the Geriatric Depression Rating Scale (GDRS). This is a primary outcome.
Timepoint [2] 400455 0
6 weeks and 12 weeks (primary timepoint) after intervention commencement.
Secondary outcome [3] 400456 0
Change in depression, as measured by the Mini International Neuropsychiatric Interview for Depression (MINI-MDD). This is a primary outcome.
Timepoint [3] 400456 0
6 weeks and 12 weeks (primary timepoint) after intervention commencement.
Secondary outcome [4] 401419 0
Change in peripheral hormone concentrations (amyloid-beta, tau proteins, serotonin, BDNF, cortisol, leptin, TNF-alpha, interleukin-6), as measured by blood sample and Enzyme-Linked Immunosorbent Assay (ELISA). This is a primary outcome.
Timepoint [4] 401419 0
12 weeks after intervention commencement.
Secondary outcome [5] 401420 0
Change in quality of life, as measured by the Quality of Life in Dementia Scale (QOL-AD).
Timepoint [5] 401420 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [6] 401421 0
Change in anxiety, as measured by the Rating Anxiety in Dementia Scale (RAID).
Timepoint [6] 401421 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [7] 401422 0
Change in psychological symptoms, as measured by the Neuropsychiatric Inventory (NPI).
Timepoint [7] 401422 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [8] 401423 0
Change in appetite and eating behaviours, as measured by the Appetite and Eating Behaviours Questionnaire (APEHQ).
Timepoint [8] 401423 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [9] 401424 0
Change in eating patterns, as measured by the 3-Day Diet History Record (DHR).
Timepoint [9] 401424 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [10] 401425 0
Change in sleep patterns, as measured by the Sleep Disorders Inventory (SDI).
Timepoint [10] 401425 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [11] 401426 0
Change in daily functioning capacity, as measured by the Bristol Activities of Daily Living Scale (BADLS).
Timepoint [11] 401426 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [12] 401427 0
Change in agitation, as measured by the Brief Agitation Rating Scale (BARS).
Timepoint [12] 401427 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [13] 401428 0
Change in aggression, as measured by the Rating Scale for Aggressive Behaviour in the Elderly (RAGE).
Timepoint [13] 401428 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [14] 401429 0
Blood pressure, as measured using an electronic sphygmomanometer.
Timepoint [14] 401429 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [15] 401430 0
Heart rate, as measured using an electronic sphygmomanometer.
Timepoint [15] 401430 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [16] 401431 0
Body mass index, measured using a stadiometer (height) and digital scale (weight).
Timepoint [16] 401431 0
6 weeks (mid-point) and 12 weeks after intervention commencement.
Secondary outcome [17] 401432 0
Waist circumference, measured using a tape measure.
Timepoint [17] 401432 0
6 weeks (mid-point) and 12 weeks after intervention commencement.

Eligibility
Key inclusion criteria
1. Community-dwelling individuals who can provide written informed consent, with a clinician confirmed primary diagnosis of early dementia made within the past 24 months. Participants must have a nominated supporting person, preferably living with them (e.g. spouse) who can assist with daily medication monitoring.
2. A Stage 3-5 rating on the Global Deterioration Scale (GDS)
3. A score of 20-26 on the Mini Mental State Exam (MMSE);
4. If taking general medications (e.g. Micardis, Advil), participants must have been taking them for a minimum of 6-12 weeks prior to the start of the trial, with no changes to medication regime during the 12-week trial period unless clinician-recommended changes are required for appropriate care.
Minimum age
55 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded on the basis of:
1. MRI contraindications, such as severe head injury, pace devices, coronary or peripheral artery stents, cochlear implants, renal insufficiency or claustrophobia;
2. Allergies to the excipient used in the formulation of the capsules;
3. Impaired liver or kidney or heart function;
4. Active suicidal ideation;
5. Intake of CBD, THC or cannabis within one month prior to participation;
6. Prior extensive use of CBD, defined as use greater than weekly for more than 3 months in the two years prior to participation;
7. A clinically relevant history of recreational cannabis use or other drugs of abuse, defined as more than three times a week for any continuous period of longer than 6 months in duration in the year prior to participation;
8. Prior history of treatment for alcohol use disorder in the year prior to participation, or a current score of 8 or higher on the Alcohol Use Disorders Identification Test (AUDIT);
9. Any current or recent diagnoses of neurological disorders other than dementia, including epilepsy or Parkinson’s disease;
10. Current use of medications that have clinically relevant interactions with the cytochrome P450 (CYP) 2C19 or CYP3A classes of liver enzymes prior to study inclusion (e.g. antipsychotics, antidepressants, anxiolytics);
11. Participation in any other clinical drug trials within 30 days of the current study;
12. Anticipated surgical needs within 3 months of participation.

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 to treatment condition involves contacting an impartial third-party researcher who holds the allocation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised into one of two treatment conditions: pure CBD (n = 30) or placebo (n = 30). Within this, participants will be pseudo-randomised to balance for gender, age and symptom severity scores. A random number list using a 1:1 ratio allocation will be generated in Excel by an impartial researcher to ensure an equal number of participants in both the CBD (n = 30) and placebo (n = 30) groups. Determining the allocation to each group will be made by the impartial researcher, who will sequentially match each recruited participant against the next available ID number. The impartial researcher will be informed of each participant’s gender, age and symptom severity (MMSE) score obtained during screening to ensure balancing across treatment arms for these variables. The impartial researcher will then inform the principal investigator of each participant’s allocation.
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
The dependent variables of interest will consist of scores on the psychometric measurements, MRI outcomes, plasma neuroendocrine factor concentrations and biometric measurements. Mixed model analyses of variance (ANOVAs) will be used to test for differences in the dependent variables of interest, with the between-subjects factors of treatment (CBD, placebo) and within-subjects factor of time (baseline, mid-point where applicable, post- treatment). Covariates will consist of, where necessary, age, sex, APOE status, plasma levels of CBD and dietary fat intake. Pearson’s and Spearman’s correlations will be used to determine relationships between variables. For these analyses, an a < .05 will be considered statistically significant. Post-hoc analyses will be conducted using Bonferroni corrections. Power calculations using the G*Power statistical tool (version 3.1.9.4) indicate that with N = 60 and a = .05, we have over 90% power to detect a medium effect size for the mixed model ANOVAs (Cohen’s d = 0.43; F-tests ANOVA repeated measures, within-between interaction, 2 groups), and we have over 80% power to detect a correlation of .45 between measures (bivariate correlation, one tail).

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/06/2022
Actual
11/08/2022
Date of last participant enrolment
Anticipated
9/01/2023
Actual
17/11/2022
Date of last data collection
Anticipated
10/04/2023
Actual
17/11/2022
Sample size
Target
60
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20446 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 35215 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 309575 0
Government body
Name [1] 309575 0
The National Health and Medical Research Council (NHMRC)
Country [1] 309575 0
Australia
Primary sponsor type
University
Name
University of Wollongong
Address
Northfields Avenue, Wollongong, NSW, 2500
Country
Australia
Secondary sponsor category [1] 310581 0
Other Collaborative groups
Name [1] 310581 0
Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE)
Address [1] 310581 0
Hunter Medical Research Institute, The University of Newcastle; University Drive, Callaghan, NSW, 2308
Country [1] 310581 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309354 0
Joint University of Wollongong and Illawarra Shoalhaven Local Health District Health and Medical
Ethics committee address [1] 309354 0
Ethics committee country [1] 309354 0
Australia
Date submitted for ethics approval [1] 309354 0
13/10/2020
Approval date [1] 309354 0
08/03/2021
Ethics approval number [1] 309354 0
2020/ETH02708

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113870 0
Prof Nadia Solowij
Address 113870 0
School of Psychology, Building 41, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2500.
Country 113870 0
Australia
Phone 113870 0
+61 2 4221 3732
Fax 113870 0
Email 113870 0
nadia@uow.edu.au
Contact person for public queries
Name 113871 0
Jessica Bartschi
Address 113871 0
School of Psychology, Building 41, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2500.
Country 113871 0
Australia
Phone 113871 0
+61 2 4221 3732
Fax 113871 0
Email 113871 0
jmills@uow.edu.au
Contact person for scientific queries
Name 113872 0
Nadia Solowij
Address 113872 0
School of Psychology, Building 41, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2500.
Country 113872 0
Australia
Phone 113872 0
+61 2 4221 3732
Fax 113872 0
Email 113872 0
nadia@uow.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
In order to maintain participant confidentiality, individual data will not be shared. Group data will only be reported.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
13063Informed consent form  jmills@uow.edu.au



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCannabidiol as a Treatment for Neurobiological, Behavioral, and Psychological Symptoms in Early-Stage Dementia: A Double-Blind, Placebo-Controlled Clinical Trial Protocol.2023https://dx.doi.org/10.1089/can.2021.0209
N.B. These documents automatically identified may not have been verified by the study sponsor.