DBS and Levodopa for Treating Freezing of Gait in Parkinson's Disease

Phase 4

Recruiting

• Conditions: Parkinson Disease; Freezing of Gait
• Interventions: Device: STIM ON plus; Drug: MED ON plus

• Registration Number: NCT06316232
• Lead Sponsor: IRCCS Istituto delle Scienze Neurologiche di Bologna

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.

Study Timeline

• Study Start: 2023-10-10
• Status Verified: 2024-03
• Study First Submitted: 2024-03-01
• Study First Submitted QC: 2024-03-11
• Last Update Submitted: 2024-03-11
• Study First Posted: 2024-03-18
• Last Update Posted: 2024-03-18
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MED ON plus/STIM ON plus	MED ON plus	Patients were evaluated in two following morning sessions under different treatment conditions: 1. MED ON plus (intervention 2) 2. STIM ON plus (intervention 1)
STIM ON plus/MED ON plus	STIM ON plus	Patients were evaluated in two following morning sessions under different treatment conditions: 1. STIM ON plus (intervention 1) 2. MED ON plus (intervention 2)
STIM ON plus/MED ON plus	MED ON plus	Patients were evaluated in two following morning sessions under different treatment conditions: 1. STIM ON plus (intervention 1) 2. MED ON plus (intervention 2)
MED ON plus/STIM ON plus	STIM ON plus	Patients were evaluated in two following morning sessions under different treatment conditions: 1. MED ON plus (intervention 2) 2. STIM ON plus (intervention 1)

Primary Outcome Measures

Name	Time	Method
Time spent with FOG during protocol	immediate post monitoring	Video-assessed reduction in the total time of FoG during the standardize walking protocol in MED ON plus or STIM ON plus condition compared to baseline.

Secondary Outcome Measures

Name	Time	Method
Trail Making test A and B	immediate post monitoring	Change in Trail Making test A and B scores during MED ON plus or STIM ON plus protocol compared to baseline.
Gait performance	immediate post monitoring	Changes in gait parameters measured by a system of 3 wearable inertial sensors, including: gait speed, stride lenght, number of step, cadence, gait variability, left-right asymmetry during MED ON plus or STIM ON plus protocol compared to baseline.
MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III	immediate post monitoring	Change in items 3.10 and 3.11 MDS UPDRS part III and total score between MED ON plus or STIM ON plus condition and baseline.
Patient global impression of change (PGI-C)	immediate post monitoring	Change in PGI-C scores on MED ON plus or STIM ON plus condition compared to baseline.
Phonemic/Semantic alternate Fluency test	immediate post monitoring	Change in during Phonemic/Semantic alternate Fluency test scores between MED ON plus or STIM ON plus condition and baseline.

Trial Locations

Locations (1)

IRCCS Istituto delle Scienze Neurologiche di Bologna; 🇮🇹 Bologna, Italy