Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000673549
Ethics application status
Approved
Date submitted
30/04/2024
Date registered
27/05/2024
Date last updated
27/05/2024
Date data sharing statement initially provided
27/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
The M&M Trial: Evaluating micronutrients and mindfulness for emotional dysregulation in children: A community-based randomised placebo-controlled trial
Scientific title
Efficacy of broad-spectrum micronutrients delivered via oral mucosa alongside an online mindfulness programme as an intervention for emotional dysregulation in children aged 6–10 years: a randomised controlled trial
Secondary ID [1] 311078 0
None
Universal Trial Number (UTN)
U1111-1305-7885
Trial acronym
M&M
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Emotional dysregulation 332223 0
Condition category
Condition code
Mental Health 328939 328939 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomly allocated to one of four groups:
1. micronutrient + active monitoring
2. micronutrient + mindfulness
3. placebo + active monitoring
4. placebo + mindfulness
The micronutrient intervention will begin first over an eight-week period, followed by the mindfulness intervention over a six-week period beginning week 3 of the micronutrient intervention. This initial eight-week period is the Randomised Controlled Trial (RCT) phase and will be followed by a second eight-week period where all participants receive micronutrients, and those who did not receive the mindfulness intervention in the RCT will now have access to the online program.

Intervention 1: Micronutrient intervention.
Participants will be randomly assigned to receive either a micronutrient formula or a placebo for eight weeks. After eight weeks, all participants will enter into an open-label phase whereby all participants can choose to take the micronutrient formula for another eight weeks. Both the micronutrients and placebo are in powdered form and are to be taken orally (dissolved on the tongue) at one powdered sachet per day (2.6g). The micronutrient intervention is a blend of 36 vitamins, minerals, and amino acids. The formula, Truehope Ultimate Sticks, is being manufactured and donated by Truehope Nutritional Support Ltd. and consists of the following ingredients: Vitamin A (as retinyl palmitate) 0.03 mg, Vitamin C (ascorbic acid) 10.00mg, Vitamin D (as cholecalciferol) 0.60 mcg, Vitamin E (as d-alpha tocopheryl succinate) 4.00 mg, Thiamin (as thiamin mononitrate) 0.30 mg, Riboflavin 0.23 mg, Niacin (as niacinamide) 1.50 mg, Vitamin B6 (as pyridoxine hydrochloride) 0.60 mg, Folic acid 0.02mg, Vitamin B12 (as cyanocobalamin) 0.02 mg, Biotin 0.02mg, Pantothenic acid (as calcium pantothenate) 0.35 mg, Calcium (as chelate) 22.00 mg, Iron (as chelate) 0.23 mg, Phosphorus (as chelate) 14.00 mg, lodine (from pacific kelp) 3.40 mcg, Magnesium (as chelate) 10.00 mg, Zinc (as chelate) 0.80 mg, Selenium (as chelate) 3.40 mcg, Copper (as chelate) 0.12 mg, Manganese (as chelate) 0.16 mg, Chromium (as chelate) 0.01 mg, Molybdenum (as chelate) 2.40 mcg, Potassium (as chelate) 4.00 mg,
Proprietary blend 27.72mg: [Choline bitartrate, DL-phenylalanine, vanadium chelate, citrus bioflavonoids, Inositol, L-glutamine, L-methionine, boron chelate, grape seed extract, ginkgo leaf extract, germanium sesquioxide, nickel chelate]
Other ingredients: erythritol, natural flavors, malic acid.

Adherence to the intervention will be assessed fortnightly with any missed dosages reported via Qualtrics.

Intervention 2: Mindfulness programme.
Participants will be randomly assigned to receive either access to an online weekly mindfulness programme or to active monitoring (treatment as usual) for eight weeks. After eight weeks, all participants in the active monitoring condition will be given access to the mindfulness programme in the open-label phase.
The mindfulness programme is an adaptation of an existing programme; Mindkiwi. The original Mindkiwi programme was created for children with ADHD and their families. The adapted programme for this study is abbreviated (6 weeks instead of 8), and has removed all reference to ADHD in order to make it generic to any child with emotion regulation challenges. It consists of weekly videos to watch which involve interactive activities to promote mindfulness such as meditation, muscle relaxation, and mindful breathing. Participants will be supplied both hard-copy materials (e.g. resources required for activities such as balloons, pens, paper etc) and online materials such as weekly worksheets. These materials have been selected specifically from the original Mindkiwi programme for use in this study.
Participation requires both the child and a nominated parent/caregiver to engage with the mindfulness videos. There are separate videos for child and parent/caregiver which can be completed at a convenient time throughout the week. Participants will have exclusive access to this programme via their unique login to the Mindkiwi website. Engagement for children per week is approximately twenty minutes. Engagement for parents/caregivers per week is approximately thirty minutes.
For participants who are randomly selected to receive this programme, only the micronutrient/placebo formula will be delivered for the first two weeks, after which the mindfulness programme will commence (hence the adapted programme being only 6 weeks instead of 8). This is to allow for the optimisation of brain function before learning takes place.
Adherence to the programme will be monitored by website analytics. Participants must complete modules and click to move on, therefore it is possible to see each participant's progress through the course at any given time. As each week has specific tasks, it will be apparent if participants have not completed the tasks required for that week. It is not possible for participants to skip modules.
Intervention code [1] 327528 0
Treatment: Other
Comparator / control treatment
Intervention 1: Placebo controlled.
The placebo is manufactured and donated by Truehope Nutritional Support Ltd. and consists of the following ingredients taken orally at a dose of 1 powdered sachet per day (2.6g):
Erythritol, natural flavours, malic acid

All participants will report on missed doses each fortnight as part of the fortnightly monitoring via Qualtrics.


Intervention 2: Active monitoring
Participants who are not randomised to the mindfulness programme in the Randomised Controlled Trial (RCT) phase will receive active monitoring. This will consist of 'treatment as usual', as they will be continually monitored fortnightly throughout the RCT phase regardless of whether they have been randomised to the micronutrient or placebo condition groups.
Control group
Placebo

Outcomes
Primary outcome [1] 336835 0
Emotion Dysregulation
Timepoint [1] 336835 0
Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, & 6 month follow up. End of RCT (week 8) is considered the primary endpoint.
Primary outcome [2] 337620 0
Global improvement
Timepoint [2] 337620 0
Weeks 4, 8 (primary endpoint), 12, 16, and 6-month follow up
Primary outcome [3] 337621 0
Emotion Dysregulation
Timepoint [3] 337621 0
Baseline, Weeks 4, 8 (primary endpoint), 12, 16, and 6-month follow up
Secondary outcome [1] 429776 0
Parental Stress
Timepoint [1] 429776 0
Baseline; Weeks 4, 8, 12, 16, and 6-month follow up
Secondary outcome [2] 429777 0
Child Sleep Habits
Timepoint [2] 429777 0
Baseline; Weeks 8, 16, and 6-Month follow up
Secondary outcome [3] 429778 0
Diet Quality
Timepoint [3] 429778 0
Baseline; Weeks 4, 8, 12, 16, and 6-Month follow up
Secondary outcome [4] 429779 0
Attentional Difficulties and Hyperactivity Symptomology
Timepoint [4] 429779 0
Baseline; Weeks 4, 8, 12, 16 and 6-month follow up
Secondary outcome [5] 429780 0
Child Anxiety.
Timepoint [5] 429780 0
Baseline. Weeks 8, 16. 6-month follow up
Secondary outcome [6] 429781 0
Parenting mindfulness
Timepoint [6] 429781 0
Baseline; weeks 2, 4, 6, 8, 10, 12, 14, 16, 6-month follow up
Secondary outcome [7] 432549 0
Stress in relation to parenting
Timepoint [7] 432549 0
Baseline; weeks 4, 8, 12, 16, and 6-month follow up
Secondary outcome [8] 432550 0
Gastrointestinal Symptoms
Timepoint [8] 432550 0
Baseline; weeks 4, 8, 12, 16, and 6-month follow up
Secondary outcome [9] 432551 0
Defiant and Oppositional Behaviour
Timepoint [9] 432551 0
Baseline; weeks 4, 8, 12, 16, and 6-month follow up.
Secondary outcome [10] 432589 0
Parental Coping
Timepoint [10] 432589 0
Baseline; weeks 8, 16 and 6-month follow up
Secondary outcome [11] 432590 0
Parental: Main Concern in Regards to their Child
Timepoint [11] 432590 0
Baseline, Weeks 4, 8, 12, 16, and 6-month follow up.
Secondary outcome [12] 432591 0
Emotional Dysregulation
Timepoint [12] 432591 0
Baseline; weeks 4, 8, 12, 16, and 6-month follow up.
Secondary outcome [13] 432592 0
Child Strengths and Difficulties
Timepoint [13] 432592 0
Baseline, Week 8, Week 16, and 6-Month follow up
Secondary outcome [14] 432593 0
Adverse Effects
Timepoint [14] 432593 0
Baseline, weeks 2, 4, 6, 8, 10, 12, 14, 16, and 6-month follow up
Secondary outcome [15] 432999 0
Microbiome
Timepoint [15] 432999 0
Baseline, Week 8 (end of RCT).
Secondary outcome [16] 433000 0
DNA Methylation
Timepoint [16] 433000 0
Baseline, Week 8 (end of RCT).
Secondary outcome [17] 433017 0
Emotional Dysregulation.
Timepoint [17] 433017 0
Baseline; weeks 2, 4, 6, 8, 10, 12, 14, 16, and 6-month follow up
Secondary outcome [18] 434801 0
Impairment Severity
Timepoint [18] 434801 0
Baseline
Secondary outcome [19] 435058 0
Parental Anxiety
Timepoint [19] 435058 0
Baseline; Weeks 4, 8, 12, 16, and 6-month follow up
Secondary outcome [20] 435059 0
Parental Depression
Timepoint [20] 435059 0
Baseline; Weeks 4, 8, 12, 16, and 6-month follow up
Secondary outcome [21] 435060 0
Child Depression
Timepoint [21] 435060 0
Baseline. Weeks 8, 16. 6-month follow up

Eligibility
Key inclusion criteria
1) Participants must meet criteria for emotional dysregulation as indicated by scores of 10 or more on the Emotion Dysregulation Inventory-Reactivity subscale (parent report) and an average score of 1 or more on the Parent-rated Affective Reactivity Index (ARI) and be assessed as moderate impairment by the Clinical Global Impression Severity (CGI-S),
2) Must be aged between 6 and 10 years of age,
3) Participants must have English competency sufficient to correctly interpret and complete study materials and questionnaires,
4) Must be medication free (psychiatric) for >4 weeks,
5) Be able to ingest 1 powder sachet per day,
6) Have at least one parent/caregiver/whanau member able to attend 6 weekly therapy sessions online with the child and access to the internet. To ensure the data collected are valid, it is important that the same parent/caregiver is available for reviews and sessions. This will be made clear in the consent meeting.
Minimum age
6 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Any serious medical or psychiatric condition potentially requiring hospitalisation,
2) Known allergy to any of the Stick or Placebo ingredients, or known abnormality of mineral metabolism (e.g., Wilson’s disease, hemochromatosis),
3) Epilepsy and,
4) Any serious mental health or behavioural concerns for either parents or child that may interrupt their ability to engage with the online programme or compromise therapeutic learning (e.g., severe conduct disorder, low intellectual functioning, traumatic brain injury, pervasive developmental disorder, severe parental substance abuse or psychiatric disorder).

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 involves contacting the holder of the allocation schedule who has no direct involvement in the study outside of allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation of 8
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
Factorial
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power analysis was conducted to determine the sample size required to detect a moderate effect size of d = 0.6, to a significance level of p = .05 at 80% power, using pre- and post-intervention measures. Based on similar previous studies on ADHD (Rucklidge et al., 2018), stress in students (Katta et al., 2023), and emotional dysregulation in children aged 5-10 (under review) which yielded effect sizes of 0.6, 1.25, and 0.54, respectively, an effect size of 0.6 is a reasonable expectation of this study. Results suggested a total sample size of 160 participants, with 40 participants per arm, would provide sufficient power to detect these effects. However this is conservative, as participant progress will be measured at multiple time points (measure-dependent) throughout the RCT, resulting in more power to detect effects compared to a pre-post design.

The repeated measures of the outcomes will be analysed using generalised linear mixed-effects regression models. These models will permit the testing of differences between the four groups (micronutrient + active monitoring, micronutrient + mindfulness, placebo + active monitoring, placebo + mindfulness) over the course of the trial. Possible moderators of the intervention(s) will also be included. These include SES, age, gender, diet, and marital status. Statistical differences between groups will utilise and report an F test. The pooled mean scores (and standard deviations) throughout the trial on each of the primary outcomes will be used to compute estimates of effect size (Cohen’s d). Chi-square analysis/odds ratios will be reported for the CGI-I by group as responder/non-responder. Scores of 1 and 2 will signify responders as ‘much improved’ or ‘very much improved’, respectively. All tests will be two-tailed, with significance levels determined as p < 0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/06/2024
Actual
Date of last participant enrolment
Anticipated
19/09/2025
Actual
Date of last data collection
Anticipated
21/08/2026
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment outside Australia
Country [1] 26027 0
New Zealand
State/province [1] 26027 0

Funding & Sponsors
Funding source category [1] 315335 0
University
Name [1] 315335 0
University of Canterbury
Country [1] 315335 0
New Zealand
Primary sponsor type
Individual
Name
Professor Julia Rucklidge
Address
University of Canterbury, 20 Kirkwood Road, Christchurch
Country
New Zealand
Secondary sponsor category [1] 317395 0
Individual
Name [1] 317395 0
Parris Theobald
Address [1] 317395 0
University of Canterbury, 20 Kirkwood Road, Christchurch
Country [1] 317395 0
New Zealand
Secondary sponsor category [2] 317486 0
Individual
Name [2] 317486 0
Alix Harding
Address [2] 317486 0
University of Canterbury, 20 Kirkwood Road, Christchurch
Country [2] 317486 0
New Zealand
Other collaborator category [1] 282983 0
Individual
Name [1] 282983 0
Dr. Mairin Taylor
Address [1] 282983 0
Country [1] 282983 0
New Zealand
Other collaborator category [2] 282984 0
Individual
Name [2] 282984 0
Professor Elena Moltchonova
Address [2] 282984 0
Country [2] 282984 0
New Zealand
Other collaborator category [3] 282985 0
Individual
Name [3] 282985 0
Dr. Aaron Stevens
Address [3] 282985 0
Country [3] 282985 0
New Zealand
Other collaborator category [4] 282986 0
Individual
Name [4] 282986 0
Dr. Katherine Donovan
Address [4] 282986 0
Country [4] 282986 0
New Zealand
Other collaborator category [5] 282987 0
Individual
Name [5] 282987 0
Associate Professor Laurie McLay
Address [5] 282987 0
Country [5] 282987 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314258 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 314258 0
Ethics committee country [1] 314258 0
New Zealand
Date submitted for ethics approval [1] 314258 0
22/12/2023
Approval date [1] 314258 0
15/03/2024
Ethics approval number [1] 314258 0

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

Contacts
Principal investigator
Name 130958 0
Prof Julia Rucklidge
Address 130958 0
University of Canterbury, 20 Kirkwood Road, Christchurch, 8140
Country 130958 0
New Zealand
Phone 130958 0
+64 33694398
Fax 130958 0
Email 130958 0
[email protected]
Contact person for public queries
Name 130959 0
Parris Theobald
Address 130959 0
University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand
Country 130959 0
New Zealand
Phone 130959 0
+64 27 435 9448
Fax 130959 0
Email 130959 0
[email protected]
Contact person for scientific queries
Name 130960 0
Julia Rucklidge
Address 130960 0
University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand
Country 130960 0
New Zealand
Phone 130960 0
+64 33694398
Fax 130960 0
Email 130960 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
Participants in this trial have not consented to their data being shared in such a way.


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.