Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000809932
Ethics application status
Approved
Date submitted
9/06/2020
Date registered
12/08/2020
Date last updated
23/11/2021
Date data sharing statement initially provided
12/08/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
The influence of white noise and dopamine on language learning in healthy young adults.
Scientific title
The influence of white noise and levodopa on language learning in healthy young adults.
Secondary ID [1] 301466 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
language learning 317785 0
Learning difficulties 317786 0
Memory difficulties 318282 0
Attention difficulties 318283 0
Condition category
Condition code
Neurological 316298 316298 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Pharmacological manipulation of dopamine (i.e., ingestion of one Madopar tablet of 125mg).

Arm 2: No pharmacological manipulation of dopamine (i.e., ingestion of a placebo tablet containing an inactive substance).

The intervention drug (i.e., Madopar) will contain two active substances: 100mg of levodopa and 25mg of benserazide.

The placebo tablet will contain an inactive substance: 125mg of

After ingesting either the Madopar tablet or placebo tablet, participants will be asked to complete an in-scanner new word learning task where half of the words (20 out of 40 new words) will be learned with auditory white noise being delivered through headphones (at approximately 70 dB on top of background scanner noise) and half of the words (20 out of 40 new words) will be learned without auditory white noise being delivered (i.e., only background scanner noise). A counterbalanced order will be used, with half of the participants in both arms learning the first block of 20 new words with white noise and the other half of the participants in both arms learning the second block of 20 new words with white noise.

The in-scanner new word learning task will take approximately 50 minutes to complete, with the first 25 minutes used to learn the first block of 20 new words (with white noise or not) and the last 25 minutes used to learn the second block of 20 new words (with white noise or not). In both blocks, participants will have 3 exposures to the 20 new words, and after each exposure, participants will complete an in-scanner recognition task to test their learning. All participants will experience all 3 exposures. Each exposure will consist of seeing the 20 new words paired with a picture, one at a time for 5 seconds. Participants will receive $1 for each new word correctly learned.

Staff involved in recruitment and delivery of the intervention include a clinical nurse, radiographer, radiologist, speech pathologist, post-doctoral research fellow and research assistant.

The intervention session will be conducted at the Herston Imaging Research Facility in Brisbane, Australia.

Intervention code [1] 317778 0
Treatment: Drugs
Intervention code [2] 317779 0
Behaviour
Intervention code [3] 317780 0
Treatment: Other
Comparator / control treatment
Between-group intervention: no pharmacological manipulation of dopamine (i.e., ingestion of one placebo tablet of 125mg containing an inactive substance),

In more detail, the placebo capsules will contain: Avicel (Microcrystalline cellulose), Riboflavin 1:10 dilution with avicel (used as a colour tag) and gelatin capsules.

In more detail, the Madopar capsules will contain: an active ingredient (madopar) plus Avicel (Microcrystalline cellulose), Riboflavin 1:10 dilution with avicel (used as a colour tag) and gelatin capsules.
Control group
Placebo

Outcomes
Primary outcome [1] 324059 0
New word recognition accuracy will be investigated. Participants will have to select the correct new word out of 4 choices displayed on a screen.
Timepoint [1] 324059 0
New word recognition accuracy will be investigated at 6 time points while in the scanner (i.e., 3 times for the first 20 new words and 3 times for the second 20 new words) and once approximately 20 minutes after the scan. The scan will start approximately 15 minutes after ingesting placebo/madopar and therefore, new word recognition accuracy will be tested approximately 20, 25, 30, 35, 40, 45 and 65 minutes post-ingestion of placebo/madopar.
Primary outcome [2] 324060 0
New word recall accuracy will be investigated. Using a laptop computer, participants will be asked to type the new words to the best of their memory.
Timepoint [2] 324060 0
New word recall accuracy will be investigated approximately 20 minutes after the end of the scan (i.e., approximately 65 minutes after ingesting the placebo/madopar capsule).
Primary outcome [3] 324242 0
New word recognition reaction time will be investigated. Response time to select the correct new word out of 4 choices will be recorded as part of the recognition tasks completed in the scanner and outside the scanner (20 minutes after the scan). Reaction time will be recorded by MATLAB software.
Timepoint [3] 324242 0
Reaction time will be recording for all 6 recognition time points performed while in the scanner and for the out of scanner recognition task performed approximately 20 minutes after the scan.
Secondary outcome [1] 383644 0
The 16 mood dimensions from Bond and Lader (1974) will be used to assess change in mood over the duration of the intervention session.
Timepoint [1] 383644 0
Prior to ingesting the placebo/madopar tablet (i.e., prior to the completing the in-scanner new word learning task) and immediately after the in-scanner new word learning task (i.e., outside the scanner).
Secondary outcome [2] 383645 0
Heart rate while learning will be measured using an MRI safe pulse-oximeter.
Timepoint [2] 383645 0
Heart rate will be collected throughout the duration of the MRI scan, while participants are learning new words, using a pulse-oximeter.
Secondary outcome [3] 384131 0
Neural correlates related to language learning brain regions and reward mechanisms will be investigated, as participants will receive $1 per correctly learned word. Whole-brain analysis will be performed and a region of interests analysis will also be performed to investigate specific brain regions such as the hippocampus, the left superior temporal gyrus and the left inferior frontal gyrus.
Timepoint [3] 384131 0
Neural correlates will be investigated using the fMRI data collected while participants performed the in-scanner new word learning task.

Eligibility
Key inclusion criteria
The inclusion criteria for this project requires that participants speak English as a first language, are aged between 18 and 35 and are right-handed, have normal or corrected-to-normal vision and/or hearing, are MRI compatible, and can safely be administered a 125 mg dose of Madopar.
Minimum age
18 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
The exclusion criteria for this project stipulates that participants will not be able to take part if they have a history of developmental learning or speech-language or other psychiatric disorder, neurological injury or disease, mental illness, currently taking neuroactive drugs for medicinal or recreational purposes (e.g., antidepressants, sedatives, stimulants, analgesics), use of hormone replacement therapy, is currently pregnant, and/or any other reason that might make it unsafe to undergo an MRI.

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 intervention (i.e., between-group placebo or Madopar, within-group white noise received first or no white noise received first and allocation to new word learning task version 1, 2 or 3) will be performed independently by an off-site researcher using the response adaptive randomization tool (RARtool) (Ryeznik, Sverdlov, & Wong, 2015) in MATLAB.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Dynamic (adaptive) random allocation method using the response adaptive randomization tool (RARtool) (Ryeznik, Sverdlov, & Wong, 2015) in MATLAB.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Mixed design with a between-group condition (i.e., placebo or Madopar) and a within-group counterbalanced condition (i.e., half of the participants will learn the first 20 new words with white noise in the background, whereas the other half of the participants will learn the first 20 new words without white noise in the background).
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
To evaluate the main aims of the research, analysis of word learning performance will utilise linear mixed effects modelling. Word recall, recognition accuracy and latency will be included as dependent variables with subject included as a random factor and group and trial as fixed factors. An alpha level of 0.05 will define statistical significance. For fMRI data obtained during the associative word learning paradigm specific regions of interest (i.e., hippocampus, the left superior temporal gyrus, the left inferior frontal gyrus) will be analysed. Whole brain analyses will also be undertaken and will examine BOLD signal changes over learning blocks and block by group (white noise vs. no white noise; Levodopa vs. placebo) interactions. The BOLD signal recorded during recognition trials and learning trials will be correlated with word learning accuracy during scanning. Covariates such as mood, heart rate, oxygen level, height, weight, body mass index, level of education, and more will be investigated.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
2/06/2020
Date of last participant enrolment
Anticipated
21/12/2020
Actual
2/12/2020
Date of last data collection
Anticipated
23/12/2020
Actual
2/12/2020
Sample size
Target
60
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 305898 0
Government body
Name [1] 305898 0
Australian Research Council
Country [1] 305898 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
St Lucia QLD 4072
Country
Australia
Secondary sponsor category [1] 306354 0
Hospital
Name [1] 306354 0
Royal Brisbane and Women's Hospital
Address [1] 306354 0
Royal Brisbane and Women’s Hospital
Cnr Butterfield St and Bowen Bridge Rd
HERSTON QLD 4029
Country [1] 306354 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306156 0
RBWH human research ethics committee
Ethics committee address [1] 306156 0
Ethics committee country [1] 306156 0
Australia
Date submitted for ethics approval [1] 306156 0
26/02/2020
Approval date [1] 306156 0
20/03/2020
Ethics approval number [1] 306156 0
2019002194

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

Contacts
Principal investigator
Name 102906 0
Prof David A. Copland
Address 102906 0
The University of Queensland Centre for Clinical Research
Building 71/918 RBWH Herston, Brisbane City QLD 4029
Country 102906 0
Australia
Phone 102906 0
+61 7 3365 2817
Fax 102906 0
Email 102906 0
[email protected]
Contact person for public queries
Name 102907 0
David A. Copland
Address 102907 0
The University of Queensland Centre for Clinical Research
Building 71/918 RBWH Herston, Brisbane City QLD 4029
Country 102907 0
Australia
Phone 102907 0
+61 7 3365 2817
Fax 102907 0
Email 102907 0
[email protected]
Contact person for scientific queries
Name 102908 0
David A. Copland
Address 102908 0
The University of Queensland Centre for Clinical Research
Building 71/918 RBWH Herston, Brisbane City QLD 4029
Country 102908 0
Australia
Phone 102908 0
+61 7 3365 2817
Fax 102908 0
Email 102908 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics approval to share individual participant data has not been obtained.


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.