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Trial registered on ANZCTR


Registration number
ACTRN12620000551998
Ethics application status
Approved
Date submitted
9/04/2020
Date registered
11/05/2020
Date last updated
11/05/2020
Date data sharing statement initially provided
11/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A micronutrient intervention for students experiencing stress
Scientific title
A randomized placebo-controlled trial investigating the efficacy of a micronutrient formula on stress in undergraduate University of Canterbury (UC) students.
Secondary ID [1] 300861 0
Nil known
Universal Trial Number (UTN)
U1111-1249-6702
Trial acronym
STAR trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stress 316767 0
Overall wellbeing 316769 0
Anxiety 316819 0
Condition category
Condition code
Mental Health 314999 314999 0 0
Anxiety
Mental Health 315387 315387 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Previous research suggests that some vitamins and minerals might help people with a variety of psychological concerns such as stress, anxiety, poor attention and low mood. One of the challenges associated with this research is that the doses are relatively high and some people don’t like or have problems with swallowing capsules. This research plans to address these challenges.
The product that will be used in this study represents a new delivery modality that has not been researched before. The Lightning Stiks are powdered candy straws that contain a micronutrient blend of vitamins, minerals, and amino acids (see below for the ingredient list for the active intervention and the matching placebo). They are simple and easy to take and are available in multiple flavours, which means that no swallowing of pills is necessary. Participants in the STAR trial will be taking Stiks that are berry flavoured. The powder is held in the mouth for 30 seconds to a minute and absorbed sublingually and then swallowed.
Participants will be taking 1 Lightning Stik or placebo per day for four weeks during RCT. After four weeks, all participants will be taking the active intervention (1 Lightning Stik per day) for another four weeks during the open-label phase.
At the end of the RCT questionnaire, we will be asking participants as to how many Stiks they have left in their sachets. They will then count them and report it back to us, which will give us an indication of their adherence to the intervention.

Ingredient list (active intervention):
Servings per Container: 30
Serving Size: 1 Stik (2.6 g)
Amount per Serving:
Vitamin A (retinyl palmitate) 0.03 mg
Vitamin C (ascorbic acid) 10.00 mg
Vitamin D (cholecalciferol) 0.60 mcg
Vitamin E (d-alpha tocopheryl succinate) 4.00 mg
Thiamin (thiamin mononitrate) 0.30 mg
Riboflavin 0.23 mg
Niacin (niacinamide) 1.50 mg
Vitamin B6 (pyridoxine hydrochloride) 0.60 mg
Folic Acid 0.02 mg
Vitamin B12 (cyanocobalamin) 0.02 mg
Biotin 0.02 mg
Pantothenic Acid (d-calcium pantothenate) 0.35 mg
Calcium (as chelate) 22.00 mg
Iron (as chelate) 0.23 mg
Phosphorus (as chelate) 14.00 mg
Iodine (from Atlantic 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 (27.72 mg):
Choline Bitartrate, DL-Phenylalanine, Vanadium Chelate, Citrus Bioflavonoids, Inositol, L-Glutamine, L-Methionine, Boron Chelate, Grape Seed Extract, Ginkgo Biloba Leaf, Germanium Sesquioxide, Nickel Chelate

Ingredient list placebo: Erythritol, Natural Flavors, Malic Acid
Intervention code [1] 317188 0
Treatment: Other
Comparator / control treatment
Placebo and control group
The study will use a randomized, double-blind, placebo-controlled design. The placebo group will take a product that looks identical compared with the active intervention, however, it contains erythritol, natural flavors, and malic acid only.
In addition, there will also be a control group of students (16 years or older) who were either not eligible for the trial or decided not to participate. They will serve as a convenient treatment-as-usual control group.
Control group
Placebo

Outcomes
Primary outcome [1] 323307 0
Stress measured with the Depression Anxiety and Stress Scale-21 (DASS). The DASS is a 21-item, publicly available questionnaire which assesses an individual’s current severity of symptoms relating to depression, anxiety and stress.
Timepoint [1] 323307 0
Screening, baseline, week 2 RCT, week 4 RCT (primary timepoint), week 6 open-label, week 8 open-label, 3 month follow-up.
Primary outcome [2] 323308 0
Modified Clinical Global Impressions Scale (CGI). The CGI is a self-administered scale that asks the participant to rate how much better/worse they feel since participation in the trial. Each item has 7 answer possibilities from very much improved to very much worse.
Timepoint [2] 323308 0
week 2 RCT, week 4 RCT (primary timepoint), week 6 open-label, week 8 open-label, 3 month follow-up
Secondary outcome [1] 381496 0
Depression (Patient Health Questionnaire-9). The PHQ-9 is a self-administered measure of depression over the last 2 weeks, including 9 items that refer to potential problems that might have occurred. How often such problems have occurred can be scored on a 0 – 3 Likert scale. By means of a 10th item, the scale also asks as to how difficult potential problems have made it for the individual to work, to take care of things at home, or to socialize.
Timepoint [1] 381496 0
baseline, week 4 RCT, week 8 open-label, 3 month follow-up
Secondary outcome [2] 381497 0
Anxiety (Generalized Anxiety Scale-7). The GAD-7 is a self-administered measure that assesses generalized anxiety disorder and screens for social anxiety, panic, and post-traumatic stress disorder (PTSD). It contains seven items, and each item can be scored from 0 - 3. The total score can range from 0 – 21, and scores of 5, 10, and 15 are used as the cut-off points for mild, moderate and severe anxiety.
Timepoint [2] 381497 0
baseline, week 4 RCT, week 8 open label, 3 month follow up
Secondary outcome [3] 381498 0
Stress (Perceived Stress Scale). The PSS measures the perception of stress and asks about thoughts and feelings during the past 4 weeks. It assesses the degree to which situations in one's life are appraised as stressful (Cohen, Kamarck, & Mermelstein, 1983; Cohen & Williamson, 1988). The PSS incorporates 10 items that can be scored on a 0 to 4 Likert Scale that refers to how often the individual feels in a certain way.
Timepoint [3] 381498 0
baseline, week 4 RCT, week 8 open-label, 3 month follow up
Secondary outcome [4] 381499 0
Wellbeing (Warwick-Edinburgh Mental Well-being Scale (WEMWBS)): A self-administered, 14 item, 1 to 5 Likert scale that measures hedonic and eudaimonic positive mental well-being over the past 2 weeks.
Timepoint [4] 381499 0
baseline, week 2 RCT, week 4 RCT, week 6 open-label, week 8 open-label, 3 month follow-up
Secondary outcome [5] 381500 0
Wellbeing (Abbreviated Profile of Mood States Questionnaire (POMS)): A 35-item scale with Likert items rated 0 – 4 that measures various aspects of mood and yields a total mood index, one positive mood index, and five negative indices.
Timepoint [5] 381500 0
baseline, week 4 RCT, week 8 open-label, 3 month follow up
Secondary outcome [6] 381502 0
Irritability (The DSM-5 Level 2-Irritability-Affective Reactivity Index (ARI)): A concise, self- or parent-report scale for the dimensional measurement of irritability. It is an adapted version of the ARI and incorporates 7 items that ask about feelings of irritability during the past seven days, and how true a statement is can be scored on a 0-2 Likert scale. It has been shown to have good internal consistency and is considered an appropriate measure to assess irritability.
Timepoint [6] 381502 0
baseline, week 4 RCT, week 8 open-label, 3 month follow up
Secondary outcome [7] 381504 0
Side effects (The Side-Effect Checklist (SEC)): Based on the Antidepressant Side Effect Checklist (ASEC), this questionnaire has been modified in the lab to assess common side effects associated with taking pills. It includes 21 items that can be scored on a 0-3 Likert scale. In addition, it asks whether it is likely that those side effects are a consequence of the intervention. Possible side effects include headaches, stomach aches, and nausea.
Timepoint [7] 381504 0
Baseline, week 2 RCT, week 4 RCT, week 6 open-label, week 8 open-label, 3 month follow-up
Secondary outcome [8] 381505 0
Alcohol consumption (Alcohol Use Disorder Identification Test (AUDIT-C)): The AUDIT-C is a 3-item alcohol screen that can help identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence), with each 5 different answer possibilities. For the purposes of this study, we have changed one of the answer possibilities for question 2: As an answer to the question: how many standard drinks containing alcohol do you have on a typical day? - an individual can now choose ‘0’ (instead of “1” in the original).
Timepoint [8] 381505 0
baseline, week 4 RCT, week 8 open-label, 3 month follow up
Secondary outcome [9] 381507 0
Life events (Impact of Events Scale Revised (IES-R)): The IES-R is a 22-item measure of commonly experienced symptoms following a distressing event. The IES-R subscales, intrusion (8 items), avoidance (8 items) and hyperarousal (6 items) correspond with the core diagnostic criteria in the DSM-IV for post-traumatic stress disorder (PTSD).
Timepoint [9] 381507 0
baseline, week 4 RCT, week 8 open-label, 3 month follow up
Secondary outcome [10] 381508 0
Sleep (The Minimal Insomnia Symptom Scale (MISS)): The MISS measures the quality of sleep by means of a 3-item, 0-4 Likert scale. Scores under a score of 6 are considered within the normal range.
Timepoint [10] 381508 0
baseline, week 2 RCT, week 4 RCT, week 6 open-label, week 8 open-label, 3 month follow-up
Secondary outcome [11] 381509 0
Diet (Dietary Screening Tool (DAST). The DAST is a measure of nutrition that assesses some daily food habits including frequency/regularity of eating breakfast, servings of fruit and vegetables, and fast food intake. It has 25 items with each having 2 to 5 answer possibilities either in form of a Likert scale or dichotomous (Yes/No) response. However, for the purposes of this study item 25, which refers to the use of nutritional supplements, will be removed from the measure.
Timepoint [11] 381509 0
Screening, baseline, week 4 RCT, week 8 open-label
Secondary outcome [12] 381510 0
Health Anxiety Inventory (HAI) (short form): The short form of the HAI comprises of 14 questions that have four answer possibilities each. We will be using the ‘week’ version of the HAI, asking participants about symptoms of health anxiety, attitudes and behaviour over the past week. For purposes of the proposed study, we have adapted the HAI to capture anxiety specific to COVID-19.

COVID 19: We will also be asking questions about the participant’s current situation and stress regarding COVID-19.
Timepoint [12] 381510 0
baseline, week 4 RCT, week 8 open-label, 3 month follow-up

Eligibility
Key inclusion criteria
1) Participants must be enrolled in an undergraduate degree at UC, 2) 16 years of age and older as long as they possess a level of understanding sufficient to complete the questionnaires and examinations required by the protocol and be considered reliable and compliant with the protocol (including the ingestion of 1 Lightning Stik/day), 3) Participants require English language competence sufficient to understand study materials and answer questionnaires, 4) Scores on the DASS-21 indicating at least mild levels of stress will be used as cut-offs for inclusion; specifically, participants will be eligible if they score 15 or above on the DASS-21 stress scale at screening (using adjusted scoring).
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Potential participants must not have been taking psychotropic medications (e.g. antidepressants) in the prior 4 weeks nor for the trial period. 2) Any serious medical condition that might require hospitalization, 3) Any participant known to be allergic to the ingredients of the Stiks or placebo, 4) Pregnancy or breastfeeding, 5) Any medication with primarily central nervous system activity, including mood stabilizers, 6) Participation in study period 1 (semester 1) in either the active intervention or placebo group will exclude participation in study period 2 (semester 2). Participants won’t be excluded if taking any hormonal contraceptives.

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)
Sealed opaque, white sachets
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
We are randomizing in blocks of 4 up to 120. That means for every 4, 2 are active and 2 are placebo
Example:
1. Active
2. Placebo
3. Placebo
4. Active
5. Active
6. Active
7. placebo
8. placebo
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
Other
Other design features
The study design is a double-blind, randomized, placebo-controlled trial (RCT) for the first four weeks of the trial, where participants are randomized to either a micronutrient or a placebo group. After four weeks, all participants will be part of an open-label phase, where everyone will knowingly take the active intervention.
We will also include a nonrandomized treatment-as-usual group - they are either not eligible for the trial or chose not to participate.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All statistical analyses will be carried out using the Statistical Package for Social Science (SPSS), Excel and Sigma Plot.
N = 120 participants will be sought for the study, split 60:60 as cohorts in Semester 1 and 2 of the university calendar year. Of the 60 participants in each cohort, n=30 will receive the active intervention and n=30 the placebo. This number of participants is sufficient to detect a moderate effect size (.5), which is a reasonable expectation as a moderate effect size has previously been detected in similar studies that investigated the effect of micronutrients on stress (Rucklidge et al., 2012 & 2014). We cannot anticipate the size of the control group – however, their data will be compared to the other two groups using the same statistical methodology as those used to compare the two RCT groups.
For the primary outcome measures (DASS-21 and Modified CGI), the repeated measures of the outcomes will be analysed using generalized linear mixed effects regression models. These models will permit the testing of differences between the micronutrient group and the placebo group over the course of the trial. The pooled mean scores (and standard deviations) throughout the trial on each of the outcomes will be used to compute estimates of effect size (Cohen’s d). For the Modified CGI, the groups will be compared at the end of the study treatment using t-tests. For secondary outcomes, linear mixed effects models will also be used. For data from randomized trials, this modelling procedure allows the researcher to fit individual-specific slopes and intercept terms, which can account for individual variability in treatment response more precisely than methods based on Analysis of Variance. The statistical test for differences between groups will be an F test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/05/2020
Actual
Date of last participant enrolment
Anticipated
1/10/2020
Actual
Date of last data collection
Anticipated
1/03/2021
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment outside Australia
Country [1] 22453 0
New Zealand
State/province [1] 22453 0
Canterbury

Funding & Sponsors
Funding source category [1] 305314 0
University
Name [1] 305314 0
University of Canterbury, School of Psychology, Speech and Hearing Research Funds
Country [1] 305314 0
New Zealand
Funding source category [2] 305336 0
Charities/Societies/Foundations
Name [2] 305336 0
University of Canterbury Foundation - donations given to the principal investigator
Country [2] 305336 0
New Zealand
Funding source category [3] 305337 0
Commercial sector/Industry
Name [3] 305337 0
True Hope
Country [3] 305337 0
Canada
Primary sponsor type
University
Name
University of Canterbury, School of Psychology, Speech, and Hearing
Address
School of Psychology, Speech, and Hearing
University of Canterbury
Private Bag 4800
Christchurch 8140
Country
New Zealand
Secondary sponsor category [1] 305680 0
None
Name [1] 305680 0
Address [1] 305680 0
Country [1] 305680 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305652 0
Health and Disability Ethics Committee
Ethics committee address [1] 305652 0
Ethics committee country [1] 305652 0
New Zealand
Date submitted for ethics approval [1] 305652 0
23/03/2020
Approval date [1] 305652 0
21/04/2020
Ethics approval number [1] 305652 0
20/NTB/70

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

Contacts
Principal investigator
Name 101098 0
Prof Julia Rucklidge
Address 101098 0
Mental Health and Nutrition Research Group Te Puna Toiora
School of Psychology, Speech and Hearing University of Canterbury
Private Bag 4800
Christchurch 8140
Country 101098 0
New Zealand
Phone 101098 0
+64 3 3694398
Fax 101098 0
Email 101098 0
[email protected]
Contact person for public queries
Name 101099 0
Nurina Maria Katta
Address 101099 0
Mental Health and Nutrition Research Group Te Puna Toiora
School of Psychology, Speech and Hearing University of Canterbury
Private Bag 4800
Christchurch 8041
Country 101099 0
New Zealand
Phone 101099 0
+64 22 010 5522
Fax 101099 0
Email 101099 0
[email protected]
Contact person for scientific queries
Name 101100 0
Julia Rucklidge
Address 101100 0
Mental Health and Nutrition Research Group Te Puna Toiora
School of Psychology, Speech and Hearing University of Canterbury
Private Bag 4800
Christchurch 8041
Country 101100 0
New Zealand
Phone 101100 0
+64 3 3694398
Fax 101100 0
Email 101100 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
This study does not ask for participants' consent to share their data beyond this study.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7446Informed consent form    379510-(Uploaded-09-04-2020-13-41-27)-Study-related document.doc
7447Study protocol    379510-(Uploaded-26-03-2020-14-38-31)-Study-related document.docx



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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No additional documents have been identified.