Efficacy and cost-effectiveness of a Transdiagnostic group-based exercise intervention: study protocol for a pragmatic multi-site randomized controlled trial

Global symptom severity will be assessed by the Global Severity Index (GSI) of the German version of the Brief Symptom Inventory [BSI-18] [58]. The GSI reflects the general mental distress rating on the symptom scales somatization, depression, and anxiety. Each symptom scale consists of 6 items. Thus, 18 items are rated on a 5-point Likert scale (range: 0–4). Higher scores indicate higher distress. Cut-off scores were evaluated separately for men (≥ 10) and women (≥ 13) and have high sensitivity (91.2%) and specificity (92.6%) [59]. Among patients with affective disorders, the GSI has demonstrated good internal consistency (α = .89) and construct validity (r = 0.71). Among patients with anxiety disorders the BSI-18 has an internal consistency of Cronbach’s α = .88 and a construct validity of r = 0.67 [60].

The secondary endpoint depressive symptoms will be assessed with the PHQ-9 module, assessing symptoms over the last two weeks with nine items, each of them representing one of the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) criteria for a depressive episode [61, 62]. All items are rated on a 4-point Likert scale (range: 0–3). The sum of all items represents the total score (range: 0–27). Higher scores indicate higher levels of depression. Regarding depressive symptomology, individuals are classified according to the degree of depression severity: absence of depressive disorder (0–4), mild degree of severity (5–10), medium major depression (10–14), severe major depression (15–19) and most severe major depression (20–27). In medical settings the cut-off of ≥10 is used to detect a major depressive disorder [61, 63]. This cut-off was shown to have a sensitivity and specificity of 88 and 85%, respectively [64]. The scale measuring depressive symptoms has an internal consistency of Cronbach’s α = .87 among a representative German sample [61, 65].

Nonorganic insomnia will be assessed with the German version of the Insomnia Severity Index [ISI] [66, 67]. The ISI consists of seven items and assesses the severity of sleep onset difficulties, sleep maintenance difficulties, early morning awakening, satisfaction with current sleep, interference with daytime functioning, noticeability of impairment attributed to sleep problems and degree of distress or concern caused by the sleep problem of the past two weeks. The total score ranges from 0 to 28 (range of component scores: 0–3), with a higher score reflecting greater insomnia severity. The cut-off score of ≥11 has shown a high sensitivity (91.4%) and specificity (84.4%) in identifying insomnia. The ISI has shown an internal consistency of Cronbach’s α = .83 among a representative German sample [66].

Sleep Quality will be assessed with the global sleep quality score of the German version of the Pittburgh Sleep Quality Index [PSQI; 68]. The global sleep quality score is the sum of seven sleep component scores (range of component scores: 0–3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. The global sleep quality score can vary from 0 to 21 with a cut-off score of 5, identifying clinically raised sleep impairment [68]. It has shown a high sensitivity (98.7%) and specificity (84.4%) in identifying insomnia [69].

The seven-item Generalized Anxiety Disorder scale [GAD-7] [70, 71] assesses symptom severity of generalized anxiety during the last 2 weeks, however shows good performance as a screening measurement for panic disorder and agoraphobia [72, 73] and will therefor serve as a measure for panic agoraphobia symptoms. Items are rated on a four-point Likert scale (range: 0–3). The sum of all items represents the total score (range: 0–21), with scores of ≥5 representing mild, scores of ≥10 moderate and scores of ≥15 severe anxiety symptom levels, respectively. The cut-off score of ≥10 has shown high sensitivity (89%) and specificity (82%) [71]. Among a representative German sample, the GAD-7 has an internal consistency of Cronbach’s α = .85 [74].

Besides the GAD-7, symptoms of panic disorder and agoraphobia symptoms will be assessed with the three-items subscale panic of the 6-items scale anxiety of the BSI-18 [58]. Current evidence suggests a four-factor structure of the BSI-18 that retains the somatization and depression symptom scales but splits the anxiety symptom scale in two factors: General anxiety and panic [75, 76]. The subscale panic of the BSI-18 consists of three items that are rated on a five-point Likert scale (range: 0–4). Among a German outpatient sample that was surveyed five times after the 2nd, 6th, 10th, 18th and 26th therapy session the best fitting model according to Akaike Information Criterion (AIC) was always the model with four factors, compared to one- and three-dimensional models [75]. Among patients with anxiety disorders, the GSI of the symptom scale anxiety has demonstrated good internal consistency (α = .83) and construct validity (r = 0.67) [60].

To assess symptoms of PTSD, the German version of the PTSD Checklist for DSM-5 (PCL-5) [77] will be used. The questionnaire is a self-report measure that consists of 20 items corresponding to the DSM-5 criteria for PTSD. Participants report their intensity of symptoms over the past four weeks on a five-point Likert scale (0 = not at all to 4 = extremely; total range 0–80). Higher scores indicate higher levels of PTSD. The German Version shows high internal consistency (α = .95), high test-retest reliability (r = .91) and a high construct validity (r = .77). A cut-off of 33 indicates clinically relevant symptomatology.

Health related quality of life will be assessed by the German version of the EQ-5D-5L questionnaire [78, 79]. It consists of five items concerning the domains mobility, self-care, usual activities, pain or discomfort and anxiety or depression with five answer alternatives each (range: 1–5). The combinations of the answer alternatives can be described with a five-digit number (i.e. the pattern 11,111 indicates the optimal health state). Through the EQ-5D-5L questionnaire Quality Adjusted Life Years (QALY) are captured for the economic evaluation. The EQ-5D-5L has an internal consistency of Cronbach’s α = .86 among German chronic heart failure patients. Current data concerning internal consistency in patients with mental disorders exists for the Spanish version of the EQ-5D-5L. Among Spanish patients with major depression the EQ-5D-5L has an internal consistency of Cronbach’s α = .77 [80].

For the economic evaluation, patients’ routine data collected 6 months before the intervention, during the time of the intervention, and six months after the intervention will be provided by the two participating statutory health insurers (AOK and TK). This data will include patients’ master data, such as gender and age, as well as patient treatment costs. Parameters for treatment costs will comprise costs of inpatient and outpatient care as well as medication, medicals aids or days of incapacity to work. Routine data for each patient will be provided for the time of the intervention as well as one year prior and one year after. The relevant costs are assessed and aggregated as quantities. In addition, cost parameters resulting from the intervention and the implementation will be considered. Subsequently, routine insurance data will be linked to primary data collected.

The assessment of self-reported exercise duration and frequency and the assessment of accelerometer -based moderate to vigorous physical activity will serve as two proxies for MVAE. Exercise in minutes per week will be assessed using the self-report Exercise Activity Index of the Physical Activity, Exercise, and Sport Questionnaire ([BSA questionnaire [81];). Participants specify type, duration, and frequency of exercise in the last four weeks. Moderate to vigorous physical activity (MVPA) will be assessed via accelerometer-based sensors (Move 4, movisens GmbH). The sensor assesses physical activity of a person based on kinematic data in three dimensions and atmospheric air pressure. This allows to estimate the amount of physical activities of different intensities for a specified time period based on validated algorithms [82]. Patients will wear the sensors for seven consecutive days. Volume of moderate to vigorous physical activity will be indicated in minutes/week and calculated by the daily physical activity of at least moderate intensity (≥ 3 MET)/minutes.

A drop-out rate less than 30% and attendance rate ≥ 80% is assumed. Attendance within the supervised (weeks 0–4; please refer to Fig. 3) and partially supervised (weeks 5–24) period will be assessed via the ImPuls smartphone application and attendance lists by the exercise therapists/study site. Participants who miss more than 4 consecutive sessions during the four weeks of the supervised phase (of weeks 0–4) of the intervention (≥40%, due to any reason) but continue the study assessments are defined as treatment-dropout, since they did not receive the intended dose of the intervention. They can still participate in the remaining sessions of the intervention and will be asked to complete all remaining assessments. Participants who miss more than 4 consecutive sessions during the four weeks of the supervised phase (of weeks 0–4) of the intervention (≥40%, due to any reason) and discontinue the study assessments will be defined as study dropout. Participants who will discontinue the treatment as well as the assessments will be defined as study dropout. All participants agree to be asked to specify their reasons for study/treatment-dropout on a voluntary basis (once, after treatment/study dropout). If available, reasons for discontinuation will be reported. If more than 50% of participants will discontinue their participation in the intervention group during the first five weeks (weeks 0–4) of the delivery, discontinuation of the group due to lack of economic efficiency for the study sites is possible. If only one participant of the intervention group remains, he or she can no longer receive the intervention, since delivery of the intervention to less than two participants no longer qualifies as “group-based intervention”.

Frequency (at least twice a week), intensity (mean intensity of least 64% of maximum heart rate) and duration (at least 30 min of MVAE in each session) of exercise during the supervised period (weeks 1–4) will be assessed via the ImPuls smartphone application.

Validated scales adapted for use in the context of ImPuls will be employed to assess patients’ outcome expectations [83], motivation [84] and satisfaction with the intervention [85], as well as exercise therapists’ motivation [86], and satisfaction with the intervention [87]. On all scales, mean scores falling within the upper quartile will be judged as indicative of high motivation for and acceptability of treatment, respectively, in patients and exercise therapists.

In addition to the goals related to investigating efficacy and cost-effectiveness of ImPuls reported in this study protocol, the overall project pursues additional goals focusing on process evaluation and implementation of ImPuls based on the Medical Research Council Guidance [57] in the routine health care system, which will be described in a separate study protocol.

The TAU condition will be modelled to represent the typical treatment patients receive in the German outpatient health care system. Therefore, patients will not be actively provided with any treatment but patients are allowed to receive any intervention that is available to them. Any evidence-based treatment provided by the outpatient mental health care system will be recorded, i.e., any psychiatric/pharmacological or psychological/psychotherapeutic intervention. Interventions, delivery or dosage of the intervention can be changed and adapted during the course of the study.

The exercise intervention “ImPuls” [88] will be delivered to groups consisting of 6 patients and will be divided into a supervised and partially-supervised period. BCTs, such as goal setting, self-monitoring, formation of concrete exercise plans and coping planning, will be integrated to promote sustained exercise behaviour change [45, 46, 89]. The intervention structure and contents are displayed in Fig. 3 and Table 1. Please also refer to the TIDieR-Checklist (Additional file 1_TIDieR-Checklist.pdf as supplementary material). Participants will receive ImPuls in addition to TAU.

Patients will participate in a combination of supervised MVAE sessions and group sessions with educative elements integrating BCTs (see Table 1) in groups with a total duration of 120 min each session. Supervised MVAE will be provided twice a week and will consist of either running or fast walking. MVAE will last 30 min and participants can choose between a standardized interval-based or endurance method protocol. Both training methods will be conducted with at least moderate intensity, which is tracked by a heart rate monitor (SIGMA iD.FREE) combined with a chest strap (SIGMA R1 Bluetooth Duo Comfortex+) and the Borg Rating of Perceived Exertion (RPE) Scale [90]. Moderate to vigorous intensity is defined as at least 64% of maximum heart rate, subtracting age from 220 [91] and at least 13 points of the RPE Scale [90]. The ImPuls smartphone application (“ImPuls-App”) developed specifically for ImPuls supports the participants and therapists during MVAE. In weeks 2, 3 and 4 patients will engage in additional 30-min MVAE, which is chosen based on their own interests and preferences. Therapists provide a list of MVAE highlights in each study site (i.e. offers in local sport clubs, yoga studio, gyms) which can be found and selected in the “ImPuls-App”.

Participants will be asked to engage in 30-min non-supervised MVAE at least twice a week. Regular MVAE will be planned through specific training schedules and accompanied by activity diaries, self-monitoring of goals and volitional strategies and weekly (weeks 5–12)/biweekly (weeks 13–24) phone calls with the exercise therapist, intending to maintain motivation, volition, and adherence to exercise. Training plans and all documentations will be executed and coordinated via the “ImPuls-App”. Information will be shared with the therapists in advance prior to the phone calls. A session for patient’s supporters (e.g., friends, partner) will be scheduled in Week 5 to inform them about the possibilities to support the participants in transforming their intentions into action.

The ImPuls App will support the participants with options for exercise planning (training plans), exercise guidance (interval training, resistance program, ratings of perceived exertion), self-monitoring of goal achievements (analysis and feedback of FITT criteria and goal achievements), mitigation of barriers and a knowledge base. A web-based application for exercise therapists will support planning and logging individual and group sessions with clients (calendar, attendance, active participation, notes). Furthermore, the participants can share some or all of their data (such as their exercise schedule or their plans for overcoming barriers) with their exercise therapists via the secure channels between the ImPuls App and the web-based platform. This will enable direct feedback of therapists to their clients. Both Apps run on Google Android and on Apple iOS. All data generated in the apps will be protected by encryption on the smartphone. All communication between smartphones (ImPuls App), browsers (Therapist’s App) and the central server will be protected by established encryption protocols, too. All components in Table 1 will be documented in or provided by the ImPuls App.

To carry out the intervention, exercise therapists will be required to have one of the following academic or comparable basic qualifications as physical activity and exercise professionals with a training period of at least 3 years: academic degree in exercise or movement science with at least 10 ECTS e.g.(i.e., 250 h) practice and 20 ECTS (i.e., 500 h) theory (e.g. Magister, Bachelor, Master, Diploma Physical Education, Exercise Science, Exercise Physiology), non-academic technical college degree Exercise and Caring/Therapeutic Gymnastics with at least 21 semester hours per week, non-academic technical college degree „Physical Educator as liberal profession“, academic and non-academic degrees in Physiotherapy. Moreover, a specific additional therapeutic qualification DVGS e.V. with 5 ECTS (i.e. 150 h) overall is required with the following content: Physical Activity-related Health Competence (2 ECTS, i.e. 100 h), Basics in Health Science and Health Pedagogy (1 ECTS; i.e. 50 h), Basics in Psychiatry, Psychosomatics and Addiction (1 ECTS, i.e. 50 h), Affective Disorders (1 ECTS, i.e. 50 h).

All exercise therapists will be trained in ImPuls and will receive a two-day and a one-day training at the University of Tuebingen. In case of missing a part of the training, therapists will be offered an individual training to catch up the missed elements. After the start of the first intervention at each study site, exercise therapists will receive a specific inhouse training within the first two weeks to discuss and solve problems and questions that arise with intervention start. After the inhouse training, exercise therapists will be offered monthly online-supervisions by two external and independent supervisors, one with a background in cognitive-behavioral therapy (CBT) and one with a background in exercise therapy. Supervision can be attended on a voluntary basis.

Study sites are local outpatient rehabilitative and medical care facilities which were selected to cover the different regions in Baden-Württemberg. They are required to have premises for the group discussions (a room for patient education, more than 12 square meters) and the supporters’ session (a suitable room for 10–20 persons; more than 30 square meters). An outdoor area for endurance-oriented exercise has to be available and emergency equipment must be on-hand. Every study site needs to have two to three employed exercise therapists with the described specific qualifications. Study sites enter into contracts with the German Association for health-related fitness and exercise therapy (DVGS e.V.) to ensure compliance to the above-mentioned structural requirements and reimbursement for conducting ImPuls.