Protocol of a randomized controlled trial investigating Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS-MODE)

(2023) 23:160 Sisodia et al. BMC Neurology https://doi.org/10.1186/s12883-023-03142-5 BMC Neurology Open Access STUDY PROTOCOL Protocol of a randomized controlled trial investigating Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS‑MODE) V. Sisodia1,2, B. E. K. S. Swinnen1,2, J. M. Dijk1,2, E. Verwijk3, G. van Rooijen2,4, A. W. Lemstra2,5, P. R. Schuurman2,6 and R. M. A. de Bie1,2*    Abstract Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor symptoms of Parkinson’s disease (PD) that persist despite optimal pharmacological treatment. Currently, DBS is not performed if there is concomitant significant cognitive impairment based on concerns of cognitive deterioration, higher complication rate and less functional improvement. However, this has not been investigated so far. Methods A single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial is being performed. Patients are eligible for the trial if they have PD dementia (PDD), are able to provide informed consent, and experience disabling motor response fluctuations, bradykinesia, dyskinesia, or painful dystonia, despite optimal pharmacological treatment. In total 44 patients will be randomized to either STN-DBS accompanied by best medical treatment (DBS group) or to best medical treatment alone (BMT group). The primary outcome measure is the change from baseline to 30 weeks on the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale part III score in a standardized off-drug phase. The main secondary outcome measures consist of scales assessing cognitive aspects of daily living, neuropsychiatric symptoms and impulsive compulsive disorders. Additional secondary outcome measures include motor signs during on-drug phase, dyskinesia, motor fluctuations, cognitive performance, (severe) adverse events, treatment satisfaction, and caregiver burden. Patients will be followed during 52 weeks after randomization. Discussion The Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBSMODE) trial directly compares the effectiveness and safety of DBS with BMT in patients with PDD. Trial registration The DBS-MODE trial has been registered in the International Clinical Trial Registry Platform (NL9361) on the 24th of March 2021 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9361). Keywords Parkinson’s disease, Dementia, Deep brain stimulation, Randomized controlled trial *Correspondence: R. M. A. de Bie Full list of author information is available at the end of the article © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Sisodia et al. BMC Neurology (2023) 23:160 Background Parkinson’s disease (PD) is a neurodegenerative disorder that affects the motor, autonomic, cognitive, affective, and sensory systems [1]. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor response fluctuations and dyskinesia that persist despite optimal pharmacological treatment [2]. After DBS surgery, patients with advanced PD generally have significant improvement of motor symptoms, functioning in daily living, and health-related quality of life (QoL). Cognitive impairment is an important and disabling feature of PD. Within ten years after diagnosis up to 70% of patients with PD will have developed PD dementia (PDD); meaning there is an obvious deficit in at least two cognitive domains impairing functioning in daily life [3, 4]. Currently, PDD is considered a relative contra-indication for treatment of motor symptoms with DBS [5]. There is a concern that DBS might worsen cognitive impairments and that the former generally routine procedure of the patient being awake during DBS surgery might be too burdensome for patients with dementia. Yet, the rationale to withhold these patients from DBS is weak and current literature even suggests otherwise. First, PD patients with mild cognitive impairment (MCI) treated with DBS do not experience a significant additional cognitive decline compared to patients who have not undergone DBS [6, 7]. The impact of DBS on cognition and development of delirium and psychosis in patients with PDD however is unclear. The current evidence consists of a case series, in which this did not seem to be an obvious issue [8]. In patients with PD who underwent DBS surgery of the nucleus basalis of Meynert aimed at improving cognitive symptoms, the risk of developing delirium and psychosis did not appear to be increased [9–11]. Second, the burden of DBS surgery has been significantly reduced now that DBS surgery of the STN under general anesthesia is becoming standardof-care and seems equally effective for motor symptom control [12–14]. Lastly, the presence of dementia is not an absolute exclusion criterion for other (invasive) procedures, such as surgery after hip fracture and dialysis for end stage renal disease [15, 16]. The improvement in motor function with DBS in PDD patients is possibly similar to PD patients without dementia [8, 17]. However, this has never been formally tested in this population and hence this is the primary objective of this pilot trial. Our main secondary objective is to investigate possible changes in cognitive functioning and psychiatric symptoms following DBS compared with best oral medical treatment (BMT). The findings of this pilot trial will help determining the merits of conducting Page 2 of 8 a future large-scale clinical trial to assess the clinical usefulness of DBS in PDD. Methods Study design The study is a single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial. The effectiveness and safety of STN DBS surgery with current standard practice of medical treatment will be assessed (Fig. 1). Patients Patients will be recruited from Amsterdam UMC, The Netherlands (...truncated)