Efficacy and long-term effects of the intervention of Zhan Zhuang Qigong on Pisa syndrome in Parkinson’s disease: the study protocol for a randomised control trial

Abstract

Introduction

Pisa syndrome (PS) is a postural abnormality that frequently manifests in various neurological disorders. In recent years, the dangers associated with Parkinson’s disease (PD) and PS have been increasingly acknowledged, leading to heightened research efforts directed toward the treatment of PS. Nevertheless, the underlying causes of PS remain complex, and no clinically effective treatments have been established. While several studies have demonstrated the significant effects of Qigong in treating PD, there is currently no evidence to support the efficacy of Qigong in the treatment of PS.

Objective

To assess the immediate and long-term effects of Zhan Zhuang Qigong on PS in participants with PD using a rigorous randomised, parallel-control design with assignment concealment and evaluator-blinding methodologies.

Methods

60 PD participants meeting the inclusion criteria will be recruited and randomly assigned to one of two groups: conventional treatment (n=30) or Zhan Zhuang Qigong (n=30). The conventional treatment group will receive standard medications and physical therapy. The Zhan Zhuang Qigong group will receive conventional medicine plus 30 min of Zhan Zhuang Qigong practiced five times per week. The long-term effects of Qigong on PS will be evaluated after 6 months and 1 year of follow-up. Assessment tools will include the NeuroPostureApp, the B-PHY(A model of a balance testing system) balance check training system, the Unified Parkinson’s Disease Rating Scale and the Parkinson’s Disease Quality of Life Questionnaire, which will measure total camptocormia, upper hump degree, Pisa angles, plantar pressure distribution, motor function and quality of life in participants with PD.

Ethics and dissemination

The local ethics committee approved this study (approval number: 2023-K068). The committee will oversee the study throughout its duration and will be notified of any protocol modifications. The results of the study will be disseminated through publication in an international journal or presentation at a conference.

Trial registration number

ChiCTR2400079696.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This is a single-centre randomised controlled trial with a limited sample size, which may lead to controversial results. Future trials should involve multiple centres and larger sample sizes to yield reproducible and robust findings.

• The study focuses on a specific population by targeting participants with Pisa syndrome (PS) who have Parkinson’s disease, while excluding those with PS secondary to other conditions.

• The study focuses solely on the effects of the intervention and does not investigate the underlying mechanisms of action.

• Staff turnover during the intervention period may introduce bias into the final results.

Introduction

Pisa syndrome (PS) is a postural disorder associated with various neurological conditions, characterised by a lateral curvature of the body that worsens during walking and may diminish with passive activity or when in the supine position.^{1 2} Its incidence is approximately 8%.^{3 4}

Due to its resemblance to the common presentation of scoliosis in the elderly,⁴ PS has historically been overlooked among cases of scoliosis, only gaining recognition by the public in the early 21st century.⁵ Increasing research indicates that PS has a distinct pathophysiology compared with camptocormia (CC), which is relevant not only to the progression and treatment of Parkinson’s disease (PD),⁶ but also significantly affects participants’ cognitive functions, reduces balance and walking ability, heightens the risk of falls and is an independent risk factor for early mortality in individuals with PD.⁴

Current clinical approaches to treating PS encompass medication, surgery and exercise rehabilitation. Botulinum toxin is among the most researched medications; however, several studies have reported unsatisfactory outcomes.⁷ Surgical interventions have been shown to be effective only in mild cases of PS,⁸ while deep brain stimulation for PD has been proposed as a contributing factor to PS.^{9 10} Furthermore, the effects of all treatment modalities—including medication and surgery—tend to dissipate within 1-year post-intervention, demonstrating a lack of lasting benefits.^{9 11}

The International Parkinson’s Disease and Movement Disorders Association emphasises the importance of early rehabilitation for PS, yet treating this condition remains a considerable challenge in motor rehabilitation for PD participants.¹² Historically, symptomatic treatments targeted potential organic causes of PS, such as alterations in core muscle strength or tone in the lumbar spine and pelvis, and sensory abnormalities regarding trunk position.13,15 However, some participants with PS exhibit no organic changes in muscle or sensory function; consequently, these symptomatic treatments have often failed to yield desired outcomes, and there is currently no unified evidence owing to the variability and contradictions across existing studies.¹⁴

Zhan Zhuang Qigong, a form of aerobic exercise focusing on spinal alignment, trunk stabilisation and limb coordination, represents a traditional Chinese exercise therapy.¹⁶ The Chinese Parkinson’s Disease Treatment Guidelines (fourth edition) recommend incorporating traditional exercise therapies, such as Tai Chi and Baduanjin, into PD rehabilitation.¹⁷ Given its relatively static and simple-to-learn nature, Zhan Zhuang Qigong is well-suited for geriatric PD participants with diminished learning capacity. Several studies have demonstrated that Zhan Zhuang Qigong significantly enhances locomotion, balance, cognition and tremor management in individuals with PD.¹⁸

Zhan Zhuang Qigong achieves spinal alignment and postural stability by actively engaging both large and small trunk muscle groups.¹⁹ This approach contrasts with passive localised treatments employed in conventional clinical practice, such as core muscle training and proprioceptive stimulation. Zhan Zhuang Qigong emphasises the unity of mind and body, coordinating high-frequency, low-amplitude antagonistic contractions of limb and trunk muscles, thereby facilitating the brain’s overall control of muscle and sensory function. This holistic approach aims to promote coordination, unity and bodily relaxation through guided practice.²⁰ Hence, it is anticipated that this treatment will exert a more significant therapeutic impact on PS, given its enigmatic aetiology, partial absence of organic changes and the difficulty of symptomatic local treatments.

Method/design

This study is a randomised, parallel-controlled, two-arm trial featuring concealed allocation and assessor blinding. The primary objective is to investigate the effects of Zhan Zhuang Qigong on PS, ultimately providing PD participants with a safe, effective, low-cost and easily accessible form of aerobic exercise therapy.

Materials and methods

Study design and setting

The study will be conducted at Nantong Fourth People’s Hospital. Recruitment will commence on 1 June 2024, and continue until 1 June 2025. It will be a parallel, single-centre, randomised, controlled trial, involving 60 participants diagnosed with PD who exhibit PS. Using a random number table, these participants will be assigned to one of two groups: a conventional treatment group and a blank control group, at a 1:1 ratio. The participants’ demographic information, including sex, age, disease duration, education level, residence status and medication usage, will be documented (figure 1).

Figure 1. Test flow chart. PDQ-39, 39-item Parkinson’s Disease Quality of Life Questionnaire; UPDRS-III, Unified Parkinson’s Disease Rating Scale, Part III.

The conventional treatment group will receive standard medications and physiotherapy five times per week for 30 min per session over the course of 8 weeks. Physiotherapy will include core muscle strength training, muscle tension reduction training and proprioceptive training.

The Zhan Zhuang Qigong group will engage in Zhan Zhuang Qigong training, with week 1 designated as the learning phase and weeks 2 through 8 as the practice phase, also participating five times per week for 30 min per session.

Zhan Zhuang Qigong movement instruction

Stand with feet approximately 30 cm apart and parallel to the midline, with knees flexed at about 10 degrees and hips flexed at approximately 10 degrees. Maintain an erect spine, wrap the arms around each other and keep a distance of approximately 15 cm between the fingertips of both hands (figure 2).

Figure 2. Demonstration of Qigong movement of Zhan Zhuang.

Recruitment strategy

The study will use two methods for participant recruitment: (1) Recruitment through rehabilitation and neurology outpatient clinics and wards; (2) announcing recruitment information through the WeChat public account and the hospital’s advertising platform. Data collection schedule and visit assessments are shown in table 1.

Table 1. Data collection schedule and visit assessments.

Measures	Baseline week	Intervention period(0–8 weeks)	End of intervention(9 weeks)	Follow-up period(6 months and 12 months)	Follow-up(6 months and 12 months later)
Participant characteristics	√
PS angle	√		√		√
Plantar pressuredistribution	√		√		√
UPDRS-III	√		√		√
PDQ-39	√		√		√
Adverse events*		√		√
Combined medication†		√		√

^*Adverse events: adverse event at any visit during treatment sessions and over the 36 weeks will be monitored. The research team will review all trial protocols, monitor patient safety and investigate any adverse events.

^†Combined medication: patients will be asked if they have used other medications during the treatment. If they have medications type and dose will be recorded. UPDRS- III: Unified Parkinson's Disease Rating Scale III; PDQ-39: 39-item Parkinson’s Disease Quality of Life Questionnaire.

PSPisa syndrome

Participants and recruitment

The diagnostic criteria for PS were established according to the 2011 Dougherty definition:²¹ (1) flexion angle >10°; (2) worsening with walking; (3) improvement with supine or passive activity; and (4) onset after the diagnosis of PD.

Inclusion criteria

1. Participants diagnosed with PD who meet the criteria outlined in the Chinese Clinical Diagnostic Criteria for PD (2016).

2. Age between 45 and 70 years.

3. Modified Hoehn-Yahr staging of stages 1–3.

4. Participants must be in a stable condition and able to remain standing after taking conventional PD medications.

5. No severe cognitive dysfunction, with the ability to learn the stance movement (Minimum Mental State Examination scores: illiterate >17, primary education >20, secondary education >22).

6. Informed consent must be obtained, and participants must agree to participate in the study and its subgroups.

Exclusion criteria

1. Participants with severe dysfunction of the heart, lungs, liver or kidneys, or those diagnosed with cancer.

2. Participants with severe knee osteoarthritis, knee trauma or other serious knee conditions that hinder the ability to stand.

3. Participants with a history of organic impairment of the spine or its associated muscles and ligaments, rendering them unsuitable for spinal training.

Criteria for termination

1. Participants who voluntarily withdraw prior to the completion of the intervention.

2. Participants whose condition deteriorates during the trial and are deemed unsuitable to continue.

3. Participants exhibiting inadequate compliance or a lack of cooperation with the treatment regimen.

Randomisation, allocation concealment and blinding

This study will employ a single-blinded design. While it is not feasible to blind participants to the Qigong intervention, evaluators will remain blinded. The implementers, evaluators and data statisticians will operate independently and will not exchange information with one another. Participants will be assigned to groups A and B using sealed envelopes, ensuring that evaluators and data statisticians are unaware of the group assignments. The blinding will be lifted by the quality monitor after data processing is completed.

Assessment results

Primary outcomes

1. Measurement of the PS angle

Participants’ postures were video-recorded following a standardised protocol. Frontal screenshots of each participant’s posture were extracted from the videos, and the PS angle was subsequently measured using NeuroPostureApp (http://www.neuroimaging.uni-kiel.de/), referencing the international consensus on angle measurements for CC.²²

• 2 1Measurement of plantar pressure distribution

Using the B-PHY (A balance testing system) type balance check training system manufactured by Changzhou Qianjing Rehabilitation Company, the ellipse area of the centre of pressure trajectory for both patient groups was measured. Participants were evaluated under two conditions: eyes open and eyes closed, with each condition measured for 30 s, followed by a 10 s rest between the evaluations.

Secondary outcomes

1. Evaluation of motor function

Participants with PD have their motor function assessed using the Unified Parkinson’s Disease Rating Scale, Part III (UPDRS-III). The UPDRS-III is comprised of 18 items, which include speech, limb movement, rigidity, locomotion, posture and tremor ratings. Each item is scored from 0 to 4, with greater scores indicating more severe symptoms.

• 2 1Quality of life assessment

The 39-item Parkinson’s Disease Quality of Life Questionnaire (PDQ-39) is used to assess the participants’ quality of life. The PDQ-39 consists of 39 items assessing 8 dimensions of cognition, communication, spirituality and daily living, with scores ranging from 0 to 4 for each item. At the conclusion of the scoring period, the scores were converted to standardised scores; higher scores are associated with a lower quality of life.

Adherence and dropouts

During the intervention, researchers will keep a journal to track the number of interventions and reasons for missed training, as well as encourage participants and their families to attend training on time. During the follow-up period, the researchers will return visits via phone, text message and other methods. In the intervention group, protocol adherence was defined as attending at least 80% of the training sessions.

Data management

The Data Monitoring Committee will be composed of an ethics committee that approves the programme. Our research team will construct a secret database that will only be accessible to key team members and the data monitoring committee, documenting all data from the time participants sign up to the end of the intervention. We will ensure that all subjects sign an informed consent form (online supplemental material 1).

Adverse events

All adverse events during the study period will be documented using a case report form. For this trial, an adverse event will be defined as an unfavourable or unexpected sign, symptom or illness related to the intervention, such as falls, muscle injuries, fractures. Adverse events will be categorised into three levels based on severity and will be treated accordingly.

Grade 1: Mild adverse reactions, subjects dizziness, chest tightness, muscle aches and pains and other symptoms of mild fatigue, subjects can tolerate, no effect on the health of the subject, no need to deal with, instruct the patient to pay attention to rest. The test can be continued.

Grade 2: The emergence of moderate adverse reactions, the subject fell, joint swelling and pain, transient dizziness, etc, the subject cannot tolerate, need to immediately suspend the test or give appropriate symptomatic treatment.

Grade 3: The emergence of severe adverse reactions that may threaten the patient’s life, such as death, disability, requiring immediate discontinuation of treatment. And immediately report to the ethics committee.

If a subject withdraws from the trial, either actively or passively, due to any adverse event, the study team will follow the subject throughout the trial until the adverse event is resolved and the original information will be recorded and filed and reported to the ethics committee.

Sample size estimation

The study is designed as a randomised controlled trial. The primary outcome is the remission rate of PS following treatment. A review of previous studies indicates that the remission rate associated with standard treatment is approximately 50%, whereas the anticipated remission rate for the intervention group following the training is estimated to be 85%. The significance level (α) is set at 0.05 (two-tailed), with a statistical power (1-β) established at 0.80 and the ratio of the control group to the intervention group is 1:1. Using Epitools, the calculated sample size is 54 (27 in each group). However, accounting for an estimated dropout rate of approximately 10%, a total of 60 participants with PS will be included.

Statistical analysis

Data will be collected at the conclusion of the 9th week of the intervention. The statistical analysis will be conducted using SPSS V.26.0 software for data processing and evaluation. Follow-up assessments will be performed 6 months and 1-year post-intervention to evaluate the long-term effects of the treatment.

Before conducting any statistical tests, the distribution of the data will be examined for normality using the Shapiro-Wilk test. If the data is normally distributed, it will be summarised using mean±SD (x̄±s). If the data does not follow a normal distribution, it will be expressed as a median and IQR.

The following statistical methods will be employed for analysis:

1. Independent t-test: This test will be used when the data is normally distributed and the variances of the two groups are equal, which will be assessed using Levene’s test for equality of variances.

2. Welch’s t-test: This test will be applied when the data is normally distributed, but the variances are unequal.

3. Wilcoxon rank-sum test: This non-parametric test will be used when the data does not conform to a normal distribution.

4. Repeated measures analysis of variance: If applicable, this will be used for comparing means across multiple time points in the follow-up assessments.

Discussion

The underlying mechanisms of PS are not yet fully understood; however, accumulating evidence suggests that central mechanisms play a significant role.23,25 Research conducted by Sasaki et al²⁶ demonstrated that PS is associated with attention deficits, executive dysfunction and vestibular imbalances in participants with PD. Participants with PS often find it more challenging to switch their focus and adapt to shifting demands.^{2 27}

During stance training, the muscles of the body engage in dynamic and continuous antagonistic contractions, requiring participants to maintain constant concentration on their weaker areas and make subtle adjustments to local muscle contractions to achieve trunk stabilisation.28,31 This process may enhance the ability of PS participants to focus and adjust their attention levels. Studies by Xinyi et al^{32 33} suggest that Zhan Zhuang Qigong can improve the selectivity and stability of practitioners’ focus.

In individuals with PS, the trunk tends to tilt to one side, leading to asymmetrical gravitational forces applied to the feet and contributing to gait and balance deficits.^{34 35} Zhan Zhuang Qigong emphasises maintaining an upright posture, thereby facilitating adjustments to ensure the torso’s alignment is symmetrical. Several studies have confirmed that standing mound Qigong can enhance spinal mobility and stability.²⁹ Jingjing’s research²⁸ indicated that Zhan Zhuang Qigong can reduce fluctuations in the centre of gravity and balance plantar pressure between the two feet. Consequently, training in Zhan Zhuang Qigong may mitigate symptoms of lateral flexion by improving spinal stability and adjusting plantar pressure distribution. In addition, Zhan Zhuang Qigong is easier to learn and safer than other traditional Chinese exercises, such as Tai Chi and Baduanjin. It can be mastered by elderly individuals in a relatively short period.³⁶

This study aims to evaluate the intervention effects and long-term impact of Zhan Zhuang Qigong on Pisa syndrome in Parkinson’s disease participants, as well as to investigate the underlying mechanisms involved. It is anticipated that this study will provide novel insights and empirical evidence for the treatment of PS.

Ethics and dissemination

The study will be conducted according to the principles of the Declaration of Helsinki and the Medical Research Involving Human Subjects Act (WMO). The study was approved by the local ethics committee (approval number: 2023-K068).

All participants should be thoroughly informed about the trial content, including the random assignment process, research design and the treatment methods and risks between the different groups. They will also be informed that they can withdraw at any time during the protocol without facing any penalties.