1.1 Study design
The study is a multicentered, four-arm, and single-blinded randomised controlled trial (RCT). The control group serves as a baseline to compare the effects of the interventions.
1.2 Participants
Inclusion criteria:
(1) Are 6- to 18-year-old school children;
(2) Have had obesity (BMI> 30 kg/m²) for at least one year;
(3) With a diagnosis of depression or apparent features of depressive symptoms as indicated by the eight-item Patient Health Questionnaire-9 (PHQ-9) scores of 10 or above (12).
Exclusion criteria:
(1) have a history of practising or receiving training in any form of mind-body or regular exercises (including tai chi, yoga, and Qigong, or regular physical activity > three times/week) during the six months before intervention;
(2) severe cognitive or language impairment as defined as a score of less than 18 on the Montreal Cognitive Assessment (MoCA) (13);
(3) undergoing electroconvulsive therapy, psychotherapy, or psychoeducation for a psychological or psychiatric condition.
Discontinuing criteria:
(1) the participants don’t want to continue;
(2) participants experience uncomfortable symptoms such as dizziness.
1.3 Study setting
To collaborate with the project team, we will conduct recruitment, intervention, and most assessments at four Hong Kong schools. The evaluations with EEG will be conducted at a school lab.
1.4 Interventions
Qigong (Eight-Section Brocades). Participants will receive 24 sessions of qigong practice over 12 weeks (2 sessions per week). Each session will last for 60 minutes. The qigong intervention will be delivered by an instructor after training by the project team. The movements of the Eight-Section Brocades are shown in Table 1—an illustration of some actions reported in a previous study (4). Table 2 summarises the plan of one session, which applies to all 24 sessions.
Mindfulness-based intervention. Participants will receive mindfulness-based intervention with the same duration and frequency as the qigong group. The intervention is adapted from Mindfulness-based Stress Reduction (14).
The mindfulness-based intervention will focus on the mind and minimise the physical component. An experienced facilitator trained by the project team will deliver the intervention. The plans for all 24 sessions are reported in Table 3. A typical session will start with the recapture of learning from the previous session (the first session will start with sharing and discussing psychological distress experienced by participants). The intervention facilitator will then introduce new mindfulness practice elements, build on old components, and guide the participants to practice for 3-5 rounds. The facilitator will ask about the participants' feelings and thoughts between the practice rounds to ensure they can follow well. Finally, all participants will share what they learned from the session.
Low-intensity physical exercise. The physical exercise group participants will receive training in low-intensity physical activities for the same duration and frequency as the qigong group. Biological activities were selected from conventional low-intensity exercise for school children. Half of the activities will train the upper limbs, and the other half will train the lower limbs. The training will be delivered by an instructor, who will train the project team. The plan of one session is summarised in Table 4 and applies to all 24 sessions.
Necessary precautions for patients participating in any one arm of interventions will be taken before commencement.
1.5 Outcomes
Primary outcomes.
(i) Depressive symptoms: The PHQ-9 (15);
(ii) Serum BDNF and plasma adiponectin: Participants will be asked to remain fasting (no eating, smoking, drinking tea or coffee for 24 hours before collecting blood samples). A peripheral blood sample will then be collected in the morning at baseline and post-intervention. Serum and plasma will be extracted from the blood and assayed with an ELISA kit. Serum BDNF will be measured in ng/mL, and plasma adiponectin will be measured in mg/L.
(iii) Obesity status: BMI: measured height and weight first and waist circumference.
Secondary outcomes.
(i) The research assistant will assess hand grip strength with a Jamar handheld dynamometer (Bolingbrook, IL) following the steps described in a previous RCT (16).
(ii) Positive and Negative Affect: Positive and Negative Affect Schedule (17)
(iii) Cognitive function: MoCA (13).
(iv) Neurophysiological measures of positive mood and attention with EEG: The eyes-closed resting state EEG of 19 electrodes, according to the International 10-20 System (18), will be assessed at baseline and post-intervention. Participants will be guided to perform diaphragmatic breathing for 5 minutes, and then, they will be asked to remain eyes-closed for another 5 minutes to capture resting state EEG data. Data will be extracted to calculate frontal alpha asymmetry (about positive mood) and intra- and interhemispheric theta coherence in front posterior and posterior brain regions (about attention) following the steps described in the previous study of DMBI (18).
Demographic and baseline characteristics.
Participants’ age, sex, ambulatory status, exercise habits, diagnosis of obesity, and trait mindfulness (Cognitive and Affective Mindfulness Scale-Revised) will be collected at baseline.
1.6 Sample size
For the main RCT comparing qigong, mindfulness, low-intensity exercise, and control groups: Since the study has 245 participants to distribute across four groups, we would divide them equally to ensure each group has a similar number of participants, which is vital for maintaining statistical power and validity in comparisons. The calculation is 245 / 4 = 61.25, so each group should start with 62 participants. The interventions will be conducted two times a week for twelve weeks.
The effect of the 12-week qigong training on baseline-to-post intervention changes in depressive symptoms and BDNF had a small to large effect size (f ranged from 15 to 56), as shown in preliminary research (9). The effect size of qigong-related changes in adiponectin in school children remains unknown, and it is reasonable to assume a small effect size. Hence, a small effect size f = 0.15 is adopted for sample size estimation. The sample size calculation will depend on the anticipated effect size, the power of the study, and the acceptable level of Type I error for each group. A power of 0.80 and Type I error of 0.0125 (as adjusted with four primary outcomes) are assumed, which should apply to each group, determining that the study has sufficient power to detect a statistically significant effect if one exists within each intervention group. According to a priori power analysis on a linear mixed model considering within-between interactions in GLIMPSE 3.0, a sample size of 196 is needed. This study needs to account for the potential dropout rate in initial recruitment to ensure that each group retains enough participants by the end of the study. The study takes an attrition rate of 20% so that it will enrol a sample of 245.
Sequential mediation models will be tested for the mediation model analysis, and the sample size will be estimated based on Monte Carlo power analysis for indirect effects (19). The correlations among changes in depressive symptoms and changes in neurobiological mediators ranged from 0.5 to 0.7 (9, 11), and r = 0.6 was adopted for sample size estimation. After assuming a power of 0.80, a sample size of 120 is needed for each mediation model. Hence, a total sample of 240 is needed to test mediation. Considering 20% attrition, the study will recruit 300 participants, powered for analyses with a linear mixed model.
For the EEG study component: Since it is preliminary to explore the effects of Qigong on EEG patterns of mood and attention, a pragmatic sample size of 30 participants from the Qigong group and 30 from the waiting-list control group will be randomly selected to obtain EEG data. This calculation is separate from the RCT and mediation model, so the study must recruit these 60 participants and the others.
In summary, the study needs to recruit
245 participants for the RCT, with 62 participants in each of the four groups (Qigong, Mindfulness, Low-Intensity Exercise, Control).
An additional 300 participants if the mediation model participants are to be different from those in the RCT.
Within the RCT, 30 participants from the Qigong group and 30 from the control group will be selected for the EEG study, but this does not require additional recruitment beyond the 245 RCT participants.
It’s crucial to ensure that the selection of participants for the EEG study does not compromise the balance and integrity of the main RCT. If the same participants are being used for the mediation models, then we must plan our analysis accordingly to ensure valid and reliable results.
1.7 Randomisation
Schools will stratify randomisation. Participants in every school will be randomly assigned to one of the following groups based on random numbers generated by IBM SPSS Statistics: (i) qigong group, (ii) mindfulness meditation group, (iii) physical exercise group, and (iv) waiting-list control group. Concealing the allocation in an RCT is crucial to ensure the study's integrity and minimise bias. A research assistant blinded to the research objectives will perform the randomisation. This allocation process reduces the likelihood of unintentional bias.
1.8 Procedures
The study assessors will be independent and blinded to treatment assignment. Assessment will be conducted at baseline and postintervention (12 weeks after baseline). Recruitment, intervention, and judgment will be conducted in three batches over 24 months (see Gantt Chart), starting September 2024. Fidelity checklists will be developed to monitor intervention fidelity at all schools.
1.9 Data management and analysis
The study utilises standardised data collection forms or electronic data capture systems. Ensure all data collectors are trained uniformly across centres to maintain consistency.
Data analysis will follow the “intention-to-treat” principle, and missing data will be replaced with values based on multiple imputations assuming a linear mixed model. Baseline variables and demographic group differences will be evaluated using a t-test or chi-square test. Separate data analysis stratified by the centre will be performed to test all hypotheses to consider centre effects for our multicenter trial. Next, the random centre effects (RCE) model (20) will be used to calculate the overall treatment effect by combining the results of individual centres. A linear mixed model will be performed to test group differences in changes in the primary outcomes from baseline to postintervention; when a significant Group × Time interaction effect emerges, post hoc analyses will be conducted to compare the changes in the preliminary results between an intervention group and wait-list control group. Mediation analyses will be performed with the IBM SPSS macro. The indirect effect of the independent variable on the dependent variable through the mediators will be tested with bootstrapping. A linear mixed model will be performed for secondary analyses to test intervention-related changes in secondary outcomes from baseline to post-intervention. The study will conduct a Pearson correlation analysis to explore the association among the differences in all primary and secondary outcomes.