Automated Mechanical Peripheral Stimulation to Treat Freezing of Gait in Patients With Parkinson's Disease and STN-DBS (AMBITION)

Automated Mechanical Peripheral Stimulation to Treat Freezing of Gait in Patients With Parkinson's Disease and Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) - a Randomized Double-blind, Sham Controlled, Cross-over Trial

The objective is to investigate whether AMPS (Automated Mechanical Peripheral Stimulation) is effective in reduction of FOG measured via the FOG-AC (Freezing Of Gait Assessment Course) in people with Parkinson Disease and STN-DBS (Subthalamic Nucleus Deep Brain Stimulation) in a randomized, double-blind, sham-controlled, cross-over trial

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Gait Disorders, Neurologic
• Intervention / Treatment: Device: GONDOLA AMPS

Detailed Description

The effects of AMPS treatment (effective vs sham) will be measured using the FOG-AC assessment. Patients will be randomized to receive either AMPS treatment and then sham or sham and then AMPS. Each treatment phase will be 4 weeks of treatment, separated by a 6-week washout period.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael Barbe, MD; Phone Number: 0221 478 7494; Email: michael.barbe@uk-koeln.de

Study Locations

• Germany
  • North Rhine-Westphalia
    • Köln, North Rhine-Westphalia, Germany, 50937
      • Recruiting
      • Uniklinik Koln
      • Contact: Elfriede Stubbs; Phone Number: +49 221 478 98842; Email: elfriede.stubbs@uk-koeln.de
      • Principal Investigator: Michael Barbe, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed Consent as documented by signature (Appendix Informed Consent Form)
• ≥18 years old
• Diagnosis of Parkinson's Disease according to the United Kingdom Brain Bank Criteria
• Bilateral STN-DBS for at least 6 months
• Moderate to severe FOG i.e. FOG-AC ≥8 pts.

Exclusion Criteria:

• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Pregnancy
• Enrolment of the investigator, his/her family members, employees and other dependent persons,
• L-Dopa induced-freezing (defined by medical history),
• DBS-induced freezing (defined by medical history),
• Clinically relevant depression
• Clinically relevant cognitive impairments
• Shoe size greater than 46

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A AMPS - sham; Treatment phase 1: AMPS Treatment phase 2: sham	Device: GONDOLA AMPS; The Gondola device is composed of two units, one per foot, each having two motors that activate rounded stimulation tips that interact with the target points. It delivers mechanical, pressure-based stimulations, sequentially in each of the four points, for the duration of 6 seconds per point. This treatment cycle is repeated 4 times, for an overall treatment duration of less than 2 minutes
Experimental: Group B sham - AMPS; Treatment phase 1: sham Treatment phase 2: AMPS	Device: GONDOLA AMPS; The Gondola device is composed of two units, one per foot, each having two motors that activate rounded stimulation tips that interact with the target points. It delivers mechanical, pressure-based stimulations, sequentially in each of the four points, for the duration of 6 seconds per point. This treatment cycle is repeated 4 times, for an overall treatment duration of less than 2 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freezing of gait assessment course	The primary outcome is the change in FOG severity measured by the freezing of gait assessment course (FOG-AC) and evaluated by a blinded observer using video recordings (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment). Min: 0 Max: 36 Higher score indicates worse symptoms.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freezing of Gait Questionnaire	FOG-Q (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment). Min: 0 Max: 24 Higher score indicates worse symptoms.	4 weeks
Timed up and go test	TUG (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment). Min: 16 Max: 64 Higher score indicates worse symptoms.	4 weeks
Movement Disorder Society - Unified Parkinson's Disease Rating Scale part I-IV	MDS-UPDRS I-IV (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment). Minimum score for all sections is 0, with higher scores indicating worse symptoms. Maximum value per section: I: 44 II: 52 III: 108 IV: 24	4 weeks
Parkinson's Disease Questionnaire	PDQ-39 (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment) Min: 0 Max: 100 Higher score indicates worse symptoms.	4 weeks
Clinical Global Impression Severity and Improvement Scores	CGI-S and CGI-I (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment). Min per scale: 1 Max per scale: 7 With higher score indicating worse symptoms.	4 weeks
Falls Efficacy Scale - International	FES-I (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment)	4 weeks
Fast 360° turns	Detection of freezing of gait in patients with Parkinson's disease (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment)	4 weeks
30-meter walk	Assessment to measure walking speed, functional mobility, gait, and vestibular function. (difference between the change after 4 weeks of effective AMPS treatment and after 4 weeks of sham-treatment)	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parkinson Neuropsychometric Dementia Assessment	PANDA Minimum value is 0, and the maximal raw scores of the subtests are associate learning immediate: 12, fluency: no maximum, working memory: 6, spatial imagery: 3, associate learning delayed: 4. Higher score indicate lesser symptoms.	Duration of study, from screening to last follow-up visit, approximately 26 weeks
Beck's Depression Inventory	BDI Min per scale: 0 Max per scale: 63 With higher score indicating worse symptoms.	Duration of study, from screening to last follow-up visit, approximately 26 weeks
Levodopa equivalent daily dose	LEDD	Throughout the duration of study, approximately 26 weeks
Deep Brain Stimulation - Total Electrical Energy Delivered	DBS TEED	Throughout the duration of study, approximately 26 weeks

Collaborators and Investigators

• Sponsor: Gondola Medical Technologies SA
• Collaborators: University of Cologne
• Investigators: Principal Investigator: Michael Barbe, MD, Department of Neurology, University Hospital Cologne

Publications and helpful links

General Publications

• Stocchi F, Sale P, Kleiner AF, Casali M, Cimolin V, de Pandis F, Albertini G, Galli M. Long-term effects of automated mechanical peripheral stimulation on gait patterns of patients with Parkinson's disease. Int J Rehabil Res. 2015 Sep;38(3):238-45. doi: 10.1097/MRR.0000000000000120.
• Quattrocchi CC, de Pandis MF, Piervincenzi C, Galli M, Melgari JM, Salomone G, Sale P, Mallio CA, Carducci F, Stocchi F. Acute Modulation of Brain Connectivity in Parkinson Disease after Automatic Mechanical Peripheral Stimulation: A Pilot Study. PLoS One. 2015 Oct 15;10(10):e0137977. doi: 10.1371/journal.pone.0137977. eCollection 2015.
• Prusch JS, Kleiner AFR, Salazar AP, Pinto C, Marchese RR, Galli M, Pagnussat AS. Automated mechanical peripheral stimulation and postural control in subjects with Parkinson's disease and freezing of gait: a randomized controlled trial. Funct Neurol. 2018 Oct/Dec;33(4):206-212.
• Pinto C, Pagnussat AS, Rozin Kleiner AF, Marchese RR, Salazar AP, Rieder CRM, Galli M. Automated Mechanical Peripheral Stimulation Improves Gait Parameters in Subjects With Parkinson Disease and Freezing of Gait: A Randomized Clinical Trial. Am J Phys Med Rehabil. 2018 Jun;97(6):383-389. doi: 10.1097/PHM.0000000000000890.
• Pagnussat AS, Salazar AP, Pinto C, Redivo Marchese R, Rieder CRM, Alves Filho JO, Franco AR, Kleiner AFR. Plantar stimulation alters brain connectivity in idiopathic Parkinson's disease. Acta Neurol Scand. 2020 Sep;142(3):229-238. doi: 10.1111/ane.13253. Epub 2020 May 5.
• Pagnussat AS, Kleiner AFR, Rieder CRM, Frantz A, Ehlers J, Pinto C, Dorneles G, Netto CA, Peres A, Galli M. Plantar stimulation in parkinsonians: From biomarkers to mobility - randomized-controlled trial. Restor Neurol Neurosci. 2018;36(2):195-205. doi: 10.3233/RNN-170744.
• Kleiner AFR, Souza Pagnussat A, Pinto C, Redivo Marchese R, Salazar AP, Galli M. Automated Mechanical Peripheral Stimulation Effects on Gait Variability in Individuals With Parkinson Disease and Freezing of Gait: A Double-Blind, Randomized Controlled Trial. Arch Phys Med Rehabil. 2018 Dec;99(12):2420-2429. doi: 10.1016/j.apmr.2018.05.009. Epub 2018 Jun 11.
• Kleiner A, Galli M, Gaglione M, Hildebrand D, Sale P, Albertini G, Stocchi F, De Pandis MF. The Parkinsonian Gait Spatiotemporal Parameters Quantified by a Single Inertial Sensor before and after Automated Mechanical Peripheral Stimulation Treatment. Parkinsons Dis. 2015;2015:390512. doi: 10.1155/2015/390512. Epub 2015 Oct 1.
• Galli M, Vicidomini C, Rozin Kleiner AF, Vacca L, Cimolin V, Condoluci C, Stocchi F, De Pandis MF. Peripheral neurostimulation breaks the shuffling steps patterns in Parkinsonian gait: a double blind randomized longitudinal study with automated mechanical peripheral stimulation. Eur J Phys Rehabil Med. 2018 Dec;54(6):860-865. doi: 10.23736/S1973-9087.18.05037-2. Epub 2018 Feb 19.
• Barbic F, Galli M, Dalla Vecchia L, Canesi M, Cimolin V, Porta A, Bari V, Cerri G, Dipaola F, Bassani T, Cozzolino D, Pezzoli G, Furlan R. Effects of mechanical stimulation of the feet on gait and cardiovascular autonomic control in Parkinson's disease. J Appl Physiol (1985). 2014 Mar 1;116(5):495-503. doi: 10.1152/japplphysiol.01160.2013. Epub 2014 Jan 16.
• Zamuner AR, Shiffer D, Barbic F, Minonzio M, Andrade CP, Corato M, Lalli S, Dipaola F, Cairo B, Albanese A, Porta A, Furlan R. Mechanical somatosensory stimulation decreases blood pressure in patients with Parkinson's disease. J Hypertens. 2019 Aug;37(8):1714-1721. doi: 10.1097/HJH.0000000000002084.

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2021
• Primary Completion (Anticipated): April 27, 2022
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Parkinson Disease; Deep Brain Stimulation; Freezing Of Gait; FOG
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Nervous System Diseases; Gait Disorders, Neurologic
• Other Study ID Numbers: UKK - AMBITION

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan

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