Description

OBJECTIVE: The PANDA trial aims to examine the feasibility, acceptability and safety of two physical activity (PA) interventions - pedometer-based walking combined with treatment as usual and karate training combined with treatment as usual - compared to treatment as usual alone. The trial will also explore a range of secondary objective and subjective outcomes. The specific objectives are to:

1. Assess feasibility for a future full-scale trial by measuring screening, recruitment, retention and attendance rates, and intervention safety.
2. Describe changes in objective (body composition and physical fitness) and subjective (patient-reported measures of emotion regulation, personality disorder symptoms and severity, interpersonal functioning, personal recovery, PA behavior, body awareness, and body image) outcomes within and between groups, to estimate the standard deviation of each outcome to inform sample size calculations for a future definitive trial.
3. Explore participant experiences using qualitative methods to assess acceptability and perceived impact of the interventions.

RECRUITMENT: Participants will be recruited from two psychotherapeutic clinics. Eligible patients will be identified during routine treatment by clinical staff based on predefined criteria. Staff will provide brief information about the trial and refer interested individuals to the research team. Additionally, potential participants may self-refer in response to posters in the two clinics. However, all self-referred patients must still meet the trial's inclusion criteria.

Detailed information about the study will then be provided in an information session, which can be conducted either in person or via telephone. Participants will have the option to be accompanied by a support person during this session. A minimum of 24 hours will be provided for reflection before scheduling the baseline visit. At the baseline visit, written informed consent will be obtained prior to any study assessments. Recruitment will continue until 60 participants are included or until July 1, 2026, whichever comes first. If fewer than 20 participants are recruited by April 1, 2026, the study will proceed as a non-randomized trial, allowing participants to select their preferred intervention arm.

STUDY VISITS: Participants will be assessed at three time points: baseline, 8 weeks, and 12 weeks. Baseline and 8-week assessments will be conducted in person, including completion of self-report questionnaires and physical measurements (body composition and cardiorespiratory fitness). The 12-week follow-up consists of questionnaires only and can be completed online at home via REDCap, with no in-person visit required.

After completing the 12-week follow-up (T2), participants originally assigned to the control or walking groups may choose to join the karate program if they wish.

SAMPLE SIZE: The trial aims to include a total of 60 participants, with 20 per arm, adhering to the sample size recommendations for feasibility and pilot trials which suggest that 15 to 25 participants per arm are needed to detect small to medium effect sizes in a subsequent main (definitive) trial with 90% power and 5% significance.

RANDOMIZATION: Eligible participants who provide written informed consent will be randomized 1:1:1 to either treatment as usual (TAU), karate plus TAU (KI+TAU), or pedometer-based walking plus TAU (PI+TAU) after the baseline assessment. Randomization will be performed using a computer-generated list created in the statistical software R and managed in Research Electronic Data Capture (REDCap) by a member of the research team not involved in the PANDA trial, ensuring that allocation remains concealed from PANDA study personnel. Randomization will be conducted in blocks of three and six throughout the study. This approach ensures that the karate intervention can start as a group of six once a total of 18 participants have been randomized, providing six participants in each study arm. Thereafter, inclusion will continue on a rolling, slow-open basis.

ANALYTICAL PLAN:

Analysis will be primarily descriptive. Quantitative outcomes will be summarized using standard methods for rates, proportions, percentages, and sample means, with means, standard deviations, and 95% confidence intervals reported for secondary outcomes at baseline, 8-week, and 12-week follow-ups for each group. Participants will be analyzed according to their allocated group regardless of post-randomization behavior (i.e., intention-to-treat analysis). Missing data will be reported, and no imputation will be performed for feasibility outcomes.

QUALITATIVE SUB-STUDY: Postintervention semi-structured individual interviews will be conducted with participants in the intervention groups. In addition, participants who withdraw from the trial will be invited to take part in an interview. An interview guide, informed by theoretical frameworks on motivation for health behavior change and the theoretical framework of acceptability including affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy will be used to explore participants' experiences of the interventions, perceived value, and barriers to engagement. Participants will be purposefully sampled. The investigators estimate that 7-8 interviews per intervention arm will be sufficient. However, the final sample size will be assessed continuously and guided by the concept of information power. Qualitative data from participant interviews will be analyzed using reflexive thematic analysis as described by Braun and Clarke, and all analyses will be conducted using appropriate software.

SAFETY: The trial will be conducted in accordance with the Declaration of Helsinki (2008), and adverse events (AEs) and serious adverse events (SAEs) will be defined according to International Council for Harmonisation - Good Clinical Practice (ICH-GCP). All participants will complete bi-weekly online questionnaires to report AEs related to the interventions, such as minor sports-related injuries during karate sessions or signs of psychological strain. Mild fatigue or lightheadedness may occur during the submaximal cycling test. Bioimpedance assessment is non-invasive, conducted according to manufacturer guidelines, and excludes participants with contraindications (e.g., pregnancy, pacemaker). Karate instructors and research staff are trained to recognize warning signs of distress or escalating tension and to respond according to predefined safety procedures. SAEs will be reported immediately to the principal investigator (JMi) and trial physician (PV), with intervention-related SAEs also reported to the Ethics Committee. Participants are monitored until resolution, with coverage provided by the Danish Patient Compensation Scheme and karate-related injuries covered by the Danish Karate Federation.

PPI: Three advisors with lived experience are involved from the inception of the PANDA trial, contributing to safety considerations, trial procedures, and the refinement and piloting of questionnaires, participant materials, and trial equipment. During the trial, advisors with lived experience will offer general guidance to support the conduct of the study and help ensure that participant perspectives are considered throughout. They will also contribute to the interpretation and communication of study results.

ETHICS: The trial follows the ethical principles of the Declaration of Helsinki and the standards of the ICH-GCP. The protocol has been approved by the Ethics Committee for the Capital Region of Denmark (H-25047904, protocol version 6) and reviewed by the Capital Region of Denmark's Research Legal Office (p-2025-20202). The study complies with the General Data Protection Regulation (GDPR) and the Data Protection Act.

Any changes to the protocol will be documented in protocol amendments, which must be approved by the Ethics Committee for the Capital Region of Denmark and reported when the study is disseminated.

The risk of serious adverse events is expected to be low. Minor adverse effects related to the interventions may occur, and appropriate monitoring will be in place to ensure participant safety. The anticipated benefits of the interventions justify conducting the trial.

FINANCES, INTEREST OF CONFLICTS AND PARTICIPANT COMPENSATION:

The PANDA Trial is funded by the Danish Council for Independent Research (DKK 1,924,524; grant number 4309-00019B) and Helsefonden, Denmark (DKK 200.000; grant number 25-B-0171). The fundings are administered through the Mental Health Centre Glostrup, covering all trial-related costs. The funders had no role in the trial design and will have no role in its conduct, analysis, reporting, or ethical oversight.

The investigators report no conflicts of interest. Participants are compensated in accordance with the guidelines of the Danish National Committee on Health Research Ethics: karate group members receive access to the 8-week program and may keep the uniform, while walking group participants receive a pedometer. Travel expenses for in-person assessments or karate sessions may be reimbursed, with no additional financial incentives offered.

DISSEMINATION: Qualitative, and quantitative results, including feasibility outcomes assessed at weeks 0, 8, and 12, will be reported in separate publications. Affect (Positive and Negative Affect Schedule \[PANAS\]) will be reported separately in an independent publication, following the publication of the primary and other secondary outcomes.