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

March 11, 2024 updated by: Ilaria Cani, IRCCS Istituto delle Scienze Neurologiche di Bologna

Efficacy of Deep Brain Stimulation and Levodopa on Freezing of Gait in Advanced Parkinson's Disease: a Comparative Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Bologna, Italy, 40139
        • Recruiting
        • IRCCS Istituto delle Scienze Neurologiche di Bologna
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Giovanna Calandra Buonaura, MD, PhD
        • Sub-Investigator:
          • Ilaria Cani, MD
        • Sub-Investigator:
          • Carlo Alberto Artusi, MD, PhD
        • Principal Investigator:
          • Giulia Giannini, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: STIM 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)
Device: STIM ON plus
increase of intensity of stimulation of 0.5 mA bilaterally
Drug: MED ON plus
administration of a 2x levodopa morning dose
Active Comparator: MED 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)
Device: STIM ON plus
increase of intensity of stimulation of 0.5 mA bilaterally
Drug: MED ON plus
administration of a 2x levodopa morning dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time spent with FOG during protocol
Time Frame: 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.
immediate post monitoring

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gait performance
Time Frame: 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.
immediate post monitoring
MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III
Time Frame: 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.
immediate post monitoring
Patient global impression of change (PGI-C)
Time Frame: immediate post monitoring
Change in PGI-C scores on MED ON plus or STIM ON plus condition compared to baseline.
immediate post monitoring
Trail Making test A and B
Time Frame: immediate post monitoring
Change in Trail Making test A and B scores during MED ON plus or STIM ON plus protocol compared to baseline.
immediate post monitoring
Phonemic/Semantic alternate Fluency test
Time Frame: immediate post monitoring
Change in during Phonemic/Semantic alternate Fluency test scores between MED ON plus or STIM ON plus condition and baseline.
immediate post monitoring

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Istituto delle Scienze Neurologiche di Bologna

Collaborators

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Investigators

  • Principal Investigator: Ilaria Cani, IRCCS Istituto delle Scienze Neurologiche di Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 1, 2024

First Submitted That Met QC Criteria

March 11, 2024

First Posted (Actual)

March 18, 2024

Study Record Updates

Last Update Posted (Actual)

March 18, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DBS-FOG 2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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