Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000717752
Ethics application status
Approved
Date submitted
11/05/2022
Date registered
19/05/2022
Date last updated
22/11/2022
Date data sharing statement initially provided
19/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effects of Cannabidiol (CBD) on Affective and Physiological Responses to Exercise in Healthy Endurance-Trained Runners
Scientific title
The Acute Effects of Cannabidiol on Affective and Physiological Responses to Exercise in Healthy Endurance-Trained Runners: A Randomised, Double-blind, Placebo-controlled, Dose-ranging, Crossover Trial
Secondary ID [1] 306259 0
CT-2022-CTN-01837-1 v2
Universal Trial Number (UTN)
U1111-1273-5212
Trial acronym
CANRUN II
Linked study record
This trial is a follow-up study of ACTRN12620000941965

Health condition
Health condition(s) or problem(s) studied:
Metabolic Disorders 325005 0
Condition category
Condition code
Metabolic and Endocrine 322441 322441 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cannabidiol (CBD) in medium chain triglyceride (MCT) oil (100mg/mL); Schedule 4 drug (contains <0.01mg/mL THC). Placebo will be MCT oil only. Treatments will be administered orally.

Arm 1: 50mg CBD (single dose); comprised of 0.5mL active oil and 2.5mL placebo oil (3mL total)
Arm 2: 300 mg CBD (single dose) comprised of 3mL active oil (3mL total)


All trials will be separated by a washout period of at least 7 days.

As this is an ‘acute dosing’ trial (i.e. using a single dose of CBD per research session) compliance does not need to be monitored.
Intervention code [1] 322674 0
Treatment: Drugs
Comparator / control treatment
Placebo; Medium Chain Triglyceride Oil (3mL)
Control group
Placebo

Outcomes
Primary outcome [1] 330219 0
Affective valence (pleasure-displeasure) on the Feelings Scale during submaximal intensity running exercise (70%VO2max; treadmill).
Timepoint [1] 330219 0
110- , 130- (primary endpoint), 150-minutes post drug administration
Secondary outcome [1] 405281 0
Oxygen consumption during submaximal intensity running exercise (~70%VO2max; treadmill), sampled using an Ultima PFX® pulmonary function system (MGC Diagnostics®).
Timepoint [1] 405281 0
90 - 150 minutes post drug administration
Secondary outcome [2] 405282 0
Maximal oxygen consumption (VO2max) sampled during a maximal intensity (incremental) running test on a treadmill, using an Ultima PFX® pulmonary function system (MGC Diagnostics®).
Timepoint [2] 405282 0
~200 minutes post drug administration
Secondary outcome [3] 405283 0
Time to exhaustion during maximal intensity running exercise (treadmill), using a built-in treadmill stopwatch.
Timepoint [3] 405283 0
~200 minutes post drug administration
Secondary outcome [4] 405304 0
Exercising heart rate (HR) measured during submaximal intensity (~70%VO2max) and maximal intensity (incremental) running exercise on a treadmill, using a chest strap HR monitor (Polar H10 HR Sensor).
Timepoint [4] 405304 0
110-, 130-, 150- and ~200-minutes post drug administration
Secondary outcome [5] 405305 0
Blood pressure at rest, measured using an automated sphygmomanometer (OMRON®, M2 Basic).
Timepoint [5] 405305 0
Baseline, 75-, ~160- and ~200-minutes post drug administration
Secondary outcome [6] 405306 0
Blood glucose (capillary) using a finger prick glucose meter.
Timepoint [6] 405306 0
110- , 130-, 150- and ~200 minutes post drug administration
Secondary outcome [7] 405309 0
Blood lactate (capillary) using a finger prick lactate analyser.
Timepoint [7] 405309 0
110- , 130-, 150- and ~200 minutes post drug administration
Secondary outcome [8] 405310 0
Score on the Profile of Mood States (POMS)
Timepoint [8] 405310 0
Baseline, 75- , 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [9] 405311 0
Score on the Spielberger 6-item State-Train Anxiety Inventory (STAI-Y)
Timepoint [9] 405311 0
Baseline, 75- , 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [10] 405312 0
Score on the Physical Activity Enjoyment Scale (PACES)
Timepoint [10] 405312 0
75- , 110-, 130-, 150- and ~200-minutes post drug administration
Secondary outcome [11] 405314 0
Ratings of Perceived Exertion (RPE) on the Borg Scale
Timepoint [11] 405314 0
110- , 130- and 150-minutes post drug administration
Secondary outcome [12] 405315 0
Gastrointestinal Comfort Visual Analogue Scale
Timepoint [12] 405315 0
Baseline, 75- , 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [13] 405318 0
Plasma cortisol concentrations
Timepoint [13] 405318 0
Baseline, 75- , 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [14] 405319 0
Plasma testosterone concentrations
Timepoint [14] 405319 0
Baseline, 75- , 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [15] 405320 0
Plasma adrenocorticotropin releasing hormone concentrations
Timepoint [15] 405320 0
Baseline, 75- , 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [16] 405323 0
Serum creatine kinase (CK) concentrations
Timepoint [16] 405323 0
Baseline, 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [17] 405324 0
Serum liposaccharide (LPS) concentrations
Timepoint [17] 405324 0
Baseline, 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [18] 405325 0
Serum Claudin-3 concentrations
Timepoint [18] 405325 0
Baseline, 150- ,~200- and ~260 minutes post drug administration
Secondary outcome [19] 408410 0
Serum Interleukin-6 (IL-6) concentrations
Timepoint [19] 408410 0
Baseline, 75- , 150-, ~200- and ~260-minutes post drug administration
Secondary outcome [20] 408411 0
Serum Interleukin-1ß (IL-1ß) concentrations
Timepoint [20] 408411 0
Baseline, 75- , 150-, ~200- and ~260-minutes post drug administration
Secondary outcome [21] 408412 0
Serum Tumour Necrosis Factor-a (TNFa) concentrations
Timepoint [21] 408412 0
Baseline, 75- , 150-, ~200- and ~260-minutes post drug administration
Secondary outcome [22] 408413 0
Plasma cannabinoid concentrations
Timepoint [22] 408413 0
Baseline, 75- ,150-, ~200- and ~260 minutes post drug administration
Secondary outcome [23] 408414 0
Plasma endocannabinoid concentrations
Timepoint [23] 408414 0
Baseline, 75- ,150-, ~200- and ~260 minutes post drug administration
Secondary outcome [24] 408415 0
Subjective ratings of muscle soreness using an 11 point Likert Scale (0 to 10)
Timepoint [24] 408415 0
24 hours post drug administration
Secondary outcome [25] 408416 0
Subjective ratings of sleep quality using an 11 point Likert Scale (-5 to +5)
Timepoint [25] 408416 0
24 hours post drug administration
Secondary outcome [26] 408417 0
Pain Visual Analogue Scale ratings
Timepoint [26] 408417 0
110- , 130- and 150-minutes post drug administration
Secondary outcome [27] 409761 0
Heart rate assessed at rest using an automated sphygmomanometer (OMRON®, M2 Basic)'
Timepoint [27] 409761 0
Baseline and 75-minutes post drug administration

Eligibility
Key inclusion criteria
(a) Healthy individuals aged between 18–45 years
(b) Endurance-trained runners, i.e., who have run an average of more than (or equal to) 40 km·wk-1 for the last month (or more) and can sustain moderate intensity running exercise for >60-minutes
(c) The use of hormonal contraception for more than (or equal to) 3 months (for females)
(d) No reported use of cannabis or cannabinoids within the past 3 months; to be confirmed by a negative urine drug screen (UDS) at the medical screening; and
(e) Proficient in English and able to provide informed consent
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
(a) Cannabis dependence or any other drug or alcohol dependence, as per the International Statistical Classification of Diseases 10th Revision (ICD)-10 criteria or at a medical doctor’s discretion;
(b) A history (self-reported) of allergic reaction (e.g. rhinitis, urticaria, contact dermatitis, anaphylaxis) to cannabis, cannabis products or cannabinoids;
(c) A history (self-reported) of a clinically significant adverse response to cannabidiol (CBD);
(d) A history of a major psychiatric disorder within the previous 12 months, as per the Diagnostic and Statistical Manual of Mental Disorders (DSM)-V criteria or at the medical doctor’s discretion, except, mild to moderate depression (score <20 on the Beck Depression Inventory [BDI]) or mild to moderate anxiety (score <16 on the Beck Anxiety Inventory [BAI]);
(e) A history of attempted suicide or current suicide ideation as determined by a score >0 on Question 9 of the Patient Health Questionnaire (PHQ)-9;
(f) A (self-reported) history of, or current, cardiovascular, respiratory, renal, neurological, gastrointestinal, or endocrinological disorders;
(g) Pregnant or lactating. All female volunteers of child-bearing potential will be required to complete a human chorionic gonadotrophin (hCG) urine screen to rule out pregnancy at the medical screening and prior to each treatment session. All females of child-bearing potential and males with female partners must agree to use a reliable form of contraception during and one month following their participation in this project
(h) A major illness or injury that interrupted their usual training routine for a period of more than (or equal to) 3 weeks during the past 3 months;
(i) Inability to refrain from using anti-inflammatory medications (4 days) prior to each treatment session;
(j) Inability to refrain from consuming alcohol (24 h) and caffeine (12 h) prior to each treatment session;
(k) Inability to refrain from using cannabis, cannabinoids and illicit drugs while participating in this project;
(l) Use of medications that may influence CBD metabolism (e.g. inducers or inhibitors of the CYP450 enzyme system);
(m) Use of medications handled by transporter proteins or CYP enzymes that are inhibited by CBD, such as anticoagulants, calcium channel blockers, beta blockers, sulfonylureas and anti-convulsants; and
(n) Required to complete mandatory drug testing for cannabis (e.g., workplace testing)
(o) Competing in a World Anti-Doping Agency (WADA) sanctioned sporting event (within 3 months).

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 involved contacting the holder of the allocation schedule who was “off-site”
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation using a table created by computer software (i.e. computerised 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
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
An a priori sample size calculation was performed using power calculation software (G*Power Version 3.1.9.6, University of Kiel, Germany). The results of our recent pilot study suggest that acute, oral CBD treatment (300 mg) increases affective valence during 60 minutes of submaximal exercise (20 minutes: Cohen’s dz = 0.770; 40 minutes: Cohen’s dz = 0.712). At a power (1-ß) of 0.80, a two-sided Bonferroni adjusted a of 0.025 (for two planned comparisons to placebo) and a similar Cohen’s dz effect of 0.70, we predict that 22 participants will be required to detect a significant effect of CBD (placebo vs 50mg, placebo vs 300mg) on affective valence at 40 minutes of fixed, submaximal exercise (~70%VO2max). A total of 25 participants will be recruited to account for attrition.

The primary outcome measure (affective valence) will be analysed using linear mixed effects models (LMEMs) that include Treatment, Time, and the Treatment × Time interaction as fixed effects (as applicable) and the participant as a random effect. Models will be generated using the restricted maximum likelihood (RML) criterion and no covariance structure will be specified (unstructured). The data will be log-transformed and reanalysed in the event that residuals are non-normally distributed (Shapiro-Wilk test, p<0.05). The first model will be retained if the log transformation does not improve normality. Two sided (Bonferroni adjusted) post hoc comparisons will be performed (to placebo, only) if a significant main effect or interaction is observed. Two a priori planned comparisons (i.e., placebo vs 300 mg CBD and placebo vs 50 mg CBD) will also be performed for the primary outcome: affective valence. As affective valence is measured at multiple time points, we propose running planned comparisons on the 40-minute time point, only – as this is expected to be the most informative. Secondary and tertiary outcomes will also be analysed using LMEMs. Statistical significance will be accepted as p<0.05. Effect sizes will be calculated as partial eta squared and Hedges g, as appropriate.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
25/07/2022
Actual
17/10/2022
Date of last participant enrolment
Anticipated
25/05/2023
Actual
Date of last data collection
Anticipated
25/07/2023
Actual
Sample size
Target
25
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 310610 0
Charities/Societies/Foundations
Name [1] 310610 0
Lambert Initiative for Cannabinoid Therapeutics
Country [1] 310610 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Camperdown, NSW, 2006
Australia
Country
Australia
Secondary sponsor category [1] 311811 0
None
Name [1] 311811 0
Address [1] 311811 0
Country [1] 311811 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310212 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 310212 0
Ethics committee country [1] 310212 0
Australia
Date submitted for ethics approval [1] 310212 0
26/10/2021
Approval date [1] 310212 0
21/12/2021
Ethics approval number [1] 310212 0
X21-0392

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

Contacts
Principal investigator
Name 116882 0
Prof Paul Haber
Address 116882 0
Royal Prince Alfred Hospital, Level 6 South Wing, King George Building, Missenden Road, Camperdown NSW 2050
Country 116882 0
Australia
Phone 116882 0
+61 2 9515 6419
Fax 116882 0
Email 116882 0
[email protected]
Contact person for public queries
Name 116883 0
Ayshe Sahinovic
Address 116883 0
University of Sydney, Room 611, Brain and Mind Centre, 94 Mallet Street, Camperdown NSW 2050
Country 116883 0
Australia
Phone 116883 0
+61 449 786 042
Fax 116883 0
Email 116883 0
[email protected]
Contact person for scientific queries
Name 116884 0
Ayshe Sahinovic
Address 116884 0
University of Sydney, Room 611, Brain and Mind Centre, 94 Mallet Street, Camperdown NSW 2050
Country 116884 0
Australia
Phone 116884 0
+61 449 786 042
Fax 116884 0
Email 116884 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Immediately following publication (via request), no end date
Available to whom?
Only researchers who provide methodologically sound proposal
Available for what types of analyses?
Only to achieve the aims of the approved proposal
How or where can data be obtained?
By contacting the principal investigator, Professor Paul Haber ([email protected]), and trial coordinator, Ayshe Sahinovic ([email protected]), via email.


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
No additional documents have been identified.