Parkinson disease (PD), an idiopathic, neurodegenerative, and progressive movement disorder, is accompanied by movement and nonmovement symptoms, such as bradykinesia, postural instability, and cognitive and mood disorders, which all negatively affect the quality of life (QoL) [1]. Furthermore, all the aforementioned PD symptoms seem to relate to the reduction of physical activity, muscle mass, and strength levels, as well as movement performance of patients with PD, thus increasing sarcopenia and frailty [2-4]. It is well accepted that systematic physical exercise enhances neuroplasticity [5]; prevents or delays frailty [4,6]; and improves symptoms such as balance, gait, and QoL in people with PD [7].

In dance, the human body and its purposefully selected movements are the basic tools for expression in various rhythmical and cultural contexts, whether artistic, educational, training, recreational, therapeutic, or religious [8,9]. As an art form expressed through movement, dance is a physical activity accompanied by musical stimuli that seems to activate the reward system [1] and has the potential to improve QoL of participants across various age groups [10], while the targeted use of auditory rhythmical information itself seems to be therapeutic for movement and nonmovement symptoms, as well as for QoL, in people with PD [11].

Humans, as social animals, have a fundamental need to belong [12], and dance-based interventions seem to reduce social isolation and loneliness among older people [13], while also facilitating their social inclusion [14], even during the social isolation caused by the COVID-19 pandemic [15]. Positive memories directly connected with dance experiences from a young age, as well as the supportive nature of dance, which enhances social interaction, and the emotional experiences that accompany the dance process, may be some of the reasons older adults prefer dance to other physical activities [16-18].

While physical exercise seems to induce neuroplasticity in people with PD [5], dance has been associated with favorable changes in the corticospinal tract, the corpus callosum, the superior longitudinal fasciculus, the dorsolateral prefrontal cortex, the bilateral putamen, the mirror neuron system, and sensorimotor pathways of healthy dancers [9,19]. Following the aforementioned effects of dance in neuroplasticity, dance in PD seems to enhance psychological flexibility (thus the person tends to adapt to environmental changes more efficiently) and creative self-efficacy (thus the person tends to think creatively and execute these thoughts) [20]. Dance, compared to other types of exercise, improves PD symptoms, such as balance, functional mobility, and cognition [21-24]. Moreover, dance is a substantial motivational means of exercise for patients with PD, enhancing their adherence rates to exercise programs [25,26], as well as a safe, feasible, and enjoyable intervention for patients with early- to midstage PD [27], even when the classes are remotely conducted [28].

Dance for Parkinson’s Disease (DfPD) is a structured dance program under appropriate care and supervision especially designed for people with PD, which integrates different dance genres [29]. Various studies have already described the content of the DfPD class that was followed [30-32]. To our knowledge, there is no published study investigating the effect of DfPD on the frailty and sarcopenia experienced by patients with PD. In addition, no randomized controlled trial to date has been conducted to investigate either the effect of this program on any clinical parameter in Greek patients with PD or the possible differential effect of in-person versus online DfPD. Furthermore, there is no published protocol of any patient-centered or culturally tailored dance intervention for the PD population showing the exact methodology that was followed and the content of the dance intervention. This study aims to fill the above gaps by publishing all the aforementioned data of our research protocol.

The primary aim of this study is to investigate the possible effectiveness of a patient-centered and culturally tailored dance intervention delivered both in-person (in-person DfPD) and remotely (online DfPD) on QoL of Greek patients with early- to midstage PD. The key secondary aim is to investigate the safety and feasibility of the aforementioned interventions (ie, in-person DfPD and online DfPD) and its possible effectiveness on fatigue, depressive symptoms, stress, anxiety, sarcopenia, frailty, balance, cognitive functions, movement and nonmovement PD symptoms, and BMI of Greek patients with early- to midstage PD.

This is a single-centered 3-arm crossover and open-label randomized controlled trial (in-person DfPD vs online DfPD vs control) of UPGRADE-PD (Upbeating Greek Application of Dance in Parkinson’s Disease). Blinding among participants and researchers is not possible due to the nature of the study. There are 6 possible research sequences, as shown in Table 1, and 3 possible carryover effects (1, 2, and 3) for each period from the prior intervention, as shown in Table 2. The study will last 10 months for each participant, including three 2-month research periods and two 2-month washout periods. Assessments will be conducted at enrollment (T₋₀=week −1), baseline periods (T₀=week 0, T₂=week 18, and T₄=week 36), and postinterventional periods (T₁=week 9, T₃=week 27, and T₅=week 45), as shown in Table 3. Allocation to each of the 6 possible sequences will occur after the completion of the first baseline assessment, as shown in the participant flow in Figure 1.

We aim at examining whether following a twice per week DfPD class in-person or remotely for 8 weeks improves the study clinical parameters compared to usual care alone. A total of 40 patients with early- to midstage PD have been randomized to undergo a total of sixteen 60-minute DfPD classes twice weekly for more than 8 weeks, both in-person and online. The study will be conducted following the ethical principles of the Declaration of Helsinki and its later amendments [33], and the Pre-emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) trial guide [34], and will conform with the CONSORT (Consolidated Standards of Reporting Trials) guidelines for randomized crossover trials [35], as shown in Figure 1, and the Standard Protocol Items Recommendations for Interventional Trials (SPIRIT) [36-38]. Eginition University Hospital Neurological Outpatient PD Clinic is the participating center, and the first participant was enrolled in April 2023.

The study protocol was approved by the Medical Ethics Committee of the Eginition University Hospital (approval 688/07.09.2022) and the Research and Ethics Committee of the University of West Attica (approval 92282/10/10/2023) and registered at ClinicalTrials.gov (NCT06220084). Written informed consent will be obtained from all participants. At the time of manuscript submission, recruitment has been concluded, but the trial is ongoing.

The inclusion criteria for patients were set as follows: (1) age ≥18 years; (2) established diagnosis of idiopathic early to moderate PD, from 0 to 2.5 according to Hoehn and Yahr stages [39]; (3) being patient of the Eginition University Hospital Neurological Outpatient PD Clinic and under a stable medication for ≥4 weeks; (4) absence of other comorbidities or conditions that seriously affect or may affect mobility (eg, musculoskeletal or cardiovascular issues, pregnancy, terminal illnesses—such as cancer) according to attending physician’s discretion; (5) ability to understand, write, and speak in Greek; (6) written consent for participating in the study; (7) a consent of attending physician for participating in an exercise program, given they are totally aware of the patient’s clinical and physical status and medications; (8) smart device (either smartphone or tablet, laptop, or computer) access for the dance intervention that will be conducted remotely; (9) absence of serious cognitive impairment, according to attending physician’s discretion.

The exclusion criteria for patients were set as follows: (1) a non-PD tremor disorder diagnosis; (2) moderate to severe PD (≥3 Hoehn and Yahr stages) [39] because of a high fall risk [40]; (3) serious health or disability issues (either physical or mental, including pregnancy), because of which exercise is not permitted or exercise instructions cannot be followed; (4) hearing issues for which patient cannot follow music or verbal guidance; (5) non-PD related mental or mobility disorder; (6) any electronic internal medical device or implant, such as a pacemaker or a deep brain stimulation, due to contraindication in the use of bio-electrical impedance analysis [41]; (7) no access of the participant or patient’s carer to any smart device (either smart phone or tablet, laptop, or computer).

A prospective, nonrandomized, uncontrolled, open-label pilot study has already been conducted in a Greek population of 16 patients with early- to midstage PD, showing that in-person DfPD is safe and feasible, and can improve QoL, as well as several movement and nonmovement PD symptoms [45]. According to the results of the above pilot clinical trial for our primary outcome (QoL), the Cohen equations for sample size calculation [124], and considering the power of the study equal to 80% and the level of statistical significance of the controls equal to the conventional limit of statistical significance (α=.05), a power analysis was applied with the a priori formula for the F test statistical control through analysis of variance with repeated measures using G*Power software (version 3.1) [125].

Taking in consideration that the number of experimental groups will be 3, the number of repeated measurements for each participant will be 6, and the average correlation coefficient between repeated measurements will be 0.64, it was estimated that for this study, which has a 1:1:1:1:1:1 distribution ratio of participants to the groups, at least 6 participants are required in each group (18 in total). On the basis of the equations that adjust the sample size to the expected dropout rate [126], which is expected to be up to the 15% acceptable value, based on the Physiotherapy Evidence Database Scale [99], the minimum sample size required to achieve the study’s primary end point (QoL) is 21 participants.

Recruitment started 6 months before the starting date of the program via relevant printed information material and health care practitioners (neurologists and nurses) of the Eginition University Hospital Neurological Outpatient Clinic. All study procedures have been discussed face-to-face individually with each potential participant before screening for eligibility by the primary researcher. The primary researcher (ME) has obtained written informed consent from the potential clinical trial participants before the study’s inclusion.

A block randomization will be conducted after the completion of the first baseline assessment (Figure 1) in equal ratio (1:1:1:1:1:1) to 1 of the 6 study sequences (ABC, BCA, CAB, ACB, BAC, or CBA), as further shown in Table 1 [127]. Concealment is ensured by keeping study material in sealed, opaque envelopes and by using paper assignment. After baseline 1 assessment completion (Figure 1), each participant will be randomized to 1 of the 6 study sequences by the data analyst, and the document with the final groups’ formation will be delivered in a sealed envelope to the principal investigator, who is the responsible for participants’ enrollment.

All assessments will be conducted face-to-face by an independent investigator to eliminate possible detection bias, except of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and Montreal Cognitive Assessment, which will be conducted face-to-face by specialized neurologists of the Eginition University Hospital Neurological Outpatient Clinic.

Participants are free to quit at any time if they wish to discontinue the study. In that case, reasons for withdrawal will be recorded, if this is possible. Participant’s enrollment will be followed by the research team’s assistance during the entire study period, including scheduling of data collection appointments, reminding of intervention’s appointments, and communicating the starting time of each research period.

Data, including consent forms, completed paper-based data files, and study notes, will be securely stored in the main investigator’s office, which will be locked. Raw data will be encrypted and stored digitally on a local computer with access rights to the main investigator. All original data will be archived for 5 years after the completion of the research and then destroyed, according to local regulations. All written data will be stored in a locked cabinet of the main investigator’s locked office for 5 years and then destroyed. Digital data will be stored on a password-protected local computer.

The primary analysis will evaluate the between group differences in total score of the Greek version of Parkinson’s Disease Questionnaire-8 after each research period. Mean (SD) or summary statistics appropriate to the distribution of the QoL total score will be reported by study group (in-person DfPD vs online DfPD vs control). Study groups will be compared in terms of QoL using mixed model repeated measures considering the correlated data from the same patient [128]. Mixed model repeated measures are robust in small sample size studies; thus, a decreased risk of type II errors occurs [129]. For all secondary end points, summary statistics will be tabulated by study group, and study groups will be compared with a statistical method appropriate to the type of the end point (eg, continuous and categorical end point). Bonferroni correction will be used to account for multiple comparisons of secondary outcomes.

A secondary analysis of the primary end point will adjust for those prerandomization variables which might reasonably be expected to be predictive of favorable QoL total score. Any deviations from the protocol will be recorded and agreed by the investigators. Missing data will not be imputed neither for primary nor secondary analyses, and no interim analyses will be conducted in this study. All the P values are 2-sided at an α level of .05. Analyses will be conducted with SPSS (version 20.0; IBM Corp) and R (version 4.4.1; R Foundation for Statistical Computing).

This is a 3-arm crossover and open-label randomized controlled trial (in-person DfPD vs online DfPD vs control), which aims to evaluate the efficacy, safety, and feasibility of a patient-centered and culturally tailored DfPD intervention delivered both in-person and online as a complementary therapy for a series of movement and nonmovement PD symptoms, as well as for QoL, sarcopenia, and frailty of Greek patients with PD.

Frailty is a state most common in older people, characterized by high vulnerability to acute stressors, such as falls, which are associated with increased hospitalization and mortality risk as well as disease severity or progress [130]. Patients with PD, accompanied by sarcopenia and frailty, seem to have lower cognitive function, movement performance, and QoL; recurrent falls; and higher fatigue, orthostatic hypotension, and inpatient mortality. Physical exercise programs seem to reduce or prevent the risk of both conditions; thus, they may improve the QoL of patients with PD [2,4,6,131]. The possible effect of DfPD on sarcopenia and frailty of Greek patients with early-to-midstage PD has not been examined. Furthermore, there is no controlled study investigating any possible differential effect of in-person and remote delivery of the aforementioned program on the QoL of patients with PD, fatigue, depressive symptoms, stress, anxiety, sarcopenia, frailty, balance, cognitive functions, movement and nonmovement PD symptoms, and BMI. We expect that our results will aid in the implementation of well-organized patient-centered and culturally tailored dance programs for patients with PD, thus providing reliable evidence for better recommendations for clinical practice.

The results of this study are expected to show the possible differential effect of a patient-centered and culturally tailored DfPD intervention, delivered in-person versus online, on several movement and nonmovement symptoms, as well as on QoL, sarcopenia, and frailty in people living with PD in Greece.