Clinical trial NCT06316232: DBS and Levodopa for Treating Freezing of Gait in Parkinson's Disease
Official title: Efficacy of Deep Brain Stimulation and Levodopa on Freezing of Gait in Advanced Parkinson's Disease: a Comparative Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Freezing of Gait
Parkinson Disease
Keywords: freezing of gait
gait disturbances
parkinson disease
Lead sponsor: IRCCS Istituto delle Scienze Neurologiche di Bologna
Sponsor class: OTHER
Collaborators: name: A.O.U. Città della Salute e della Scienza
First posted: 2024-03-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In addition to baseline gait assessment performed in a morning session on MED ON/STIM ON condition (after usual levodopa morning dose and usual parameters of stimulation), patients are evaluated in two following morning sessions under different treatment conditions:

1. STIM ON plus: evaluation after the administration of levodopa morning dose and the increase of intensity of stimulation of 0.5 mA bilaterally,
2. MED ON plus: evaluation after the administration of a 2x levodopa morning dose with usual parameters of stimulation.
Primary purpose: TREATMENT

Brief summary: Freezing of gait (FoG) is a complex symptom of Parkinson's disease (PD) that cause falls and disability in PD patients, heavily affect patients' autonomy and quality of life. Gait disturbances and FoG are difficult to manage as they usually do not complete respond to both dopaminergic treatment and subthalamic nucleus deep brain stimulation (STN-DBS). One therapeutic strategy suggested in literature for improving gait disturbances is to increase the dose of dopaminergic drugs according to the hypothesis of pseudo-ON-freezing. The pseudo-ON-FoG in patients treated with STN-DBS can easily occur as the result of a suboptimal stimulation or the consequence of a post-operative reduction of the dopaminergic therapy. Therefore, it is reasonable hypothesize both the increase of stimulation and levodopa as good therapeutic strategies to improve pseudo-ON-FoG. At present there are no evidence for suppose that one option is better than the other, even though two recent studies on gait analysis reported a positive additive effect of levodopa therapy on gait parameters in patients treated with STN-DBS.

In this study, the investigators aim to objectively evaluating the improvement of FoG in PD patients treated with STN-DBS at different treatment conditions consisting of increased intensity of stimulation or higher dosage of levodopa.

Detailed description: This is a cross-over, blind, randomized study to evaluate the improvement of FoG in a group of PD patients treated with bilateral STN-DBS by increasing the intensity of stimulation (STIM plus) or administering a higher dose of levodopa (MED plus).

Patient will be videorecorded for evaluation of freezing episodes and gait cinematic parameters by means of 3 wearable inertial sensors on the feet and at lumbar level during a standardized walking protocol including: Timed Up and Go, Turn 360°, Gait 18 m and a Complex task in single task and dual task (serial-3 subtractions) conditions. In each condition, Tinetti scale, Trail Making Test, alternate fluency test, Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and MDS Unified Dyskinesia Rating Scale (UDysRS) will be also perform.

In addition, other demographic and clinical information such as age, sex, MMSE, MoCA, New Freezing of Gait Questionnaire, Falls Efficacy Scale will be collected.

The primary endpoint of this study is to investigate the efficacy of increasing intensity of stimulation (STIM plus) or levodopa (MED plus) on freezing of gait (FOG).

Secondary outcome measures include cinematic gait parameters, global motor outcomes and cognitive functions.

Eligibility criteria: Inclusion Criteria:

* Patients with Parkinson's disease treated with STN-DBS who achieved a good control of motor fluctuations and cardinal motor symptoms (bradykinesia, rigidity, tremor)
* History of FoG in daily-ON condition after optimal DBS programming, defined by a score of 1 on Question 1 and score ≥ 2 on Question 2 of the New Freezing of Gait Questionnaire.

Exclusion Criteria:

* inability to walk independently for 10 meters.
* limited therapeutic windows of stimulation without the possibility of increase the intensity of stimulation of 0,5 mA for the appearance of side effects
* previous evidence of severe adverse effects with high levodopa dose ore increased STN-DBS intensity, such as psychosis, hallucinations, painful dyskinesias, severe hypotension, digestive symptoms.
* dementia (MMSE score ≤ 18)

Primary outcomes:
measure: Time spent with FOG during protocol
timeFrame: immediate post monitoring
Secondary outcomes:
measure: Gait performance
timeFrame: immediate post monitoring
measure: MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
timeFrame: immediate post monitoring
measure: Patient global impression of change (PGI-C)
timeFrame: immediate post monitoring
measure: Trail Making test A and B
timeFrame: immediate post monitoring
measure: Phonemic/Semantic alternate Fluency test
timeFrame: immediate post monitoring
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna
Study officials:
affiliation: IRCCS Istituto delle Scienze Neurologiche di Bologna
name: Ilaria Cani
role: PRINCIPAL_INVESTIGATOR
References: