directSTIM™ Deep Brain Stimulation System Post-Market Clinical Follow-up Study on Essential Tremor

A Prospective, Multi-center, Single Arm, Observational, Post-market Clinical Follow-up Study on the Use of the directSTIM™ Deep Brain Stimulation System to Treat Essential Tremor

This is a prospective, multi-center, single arm post-market clinical follow-up study.

The present study investigates a product authorized on the European market that will be used per its intended use, and all procedures involved follow the standard of care.

This is an observational study to provide clinical evidence in support of DBS effectiveness in the treatment of ET when delivered by the directSTIM DBS system.

Twenty-one patients will be enrolled in this study. Subjects selected to participate in the study will be ET patients referred to uni- or bilateral DBS implant who meet the inclusion criteria and none of the exclusion criteria.

Primary effectiveness variables will be measured at baseline for the identification of the worst limb (most affected by the disease), then 3 months post-surgery. Safety events will be collected between implant and 3-month visit, to evaluate potential confounding factors.

After completing the 3-month visit, subjects will exit the study, and continue to be followed by their physician per usual care.

Study will be conducted at minimum 3 centers in Europe.

Study Overview

• Status: Terminated
• Conditions: Essential Tremor
• Intervention / Treatment: Device: Deep Brain Stimulation

Detailed Description

This study investigates the benefits and safety of the use of the directSTIM Deep Brain Stimulation (DBS) system within its intended use, to deliver DBS therapy to patients suffering from Essential Tremor (ET) whose motor symptoms are no longer optimally controlled through pharmaceutical treatment.

The objective of this study is to show that directSTIM is not inferior to competitor DBS Systems at alleviating postural or kinetic symptoms of Essential Tremor through the delivery of Deep Brain Stimulation therapy.

Data to be analyzed will be collected from ET patients referred for DBS surgery, who chose to get the directSTIM DBS System implanted after discussing its risks and benefits with their clinician.

All procedures involving the patient and the device follow the standard of care in place at the site for DBS.

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Münster, Germany, 48149
    • Universitätsklinikum Münster

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Twenty-one patients suffering from Essential Tremor, referred for DBS surgery, who chose directSTIM, will be enrolled in a minimum of 3 sites in Europe to collect primary safety and effectiveness variables baseline and 3 months post-surgery.

The sample size has been determined for the primary effectiveness endpoint. Study subjects will be representative of the target population since they will be recruited among patients who discussed the need and agreed with their clinician upon the implant of a DBS System to treat their motor symptoms caused by Essential Tremor.

Description

Inclusion Criteria:

• Patient is 18 years of age or older.
• Patient with main tremor symptoms in upper limbs.
• Patient was referred for DBS surgery to treat Essential Tremor and chose the directSTIM DBS System
• Patient has a postural or kinetic tremor severity score of at least 3 out of 4 in the extremity intended for treatment on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor with medication, for the worst limb (i.e. most affected by disease)
• Patient accepts to abstain from caffeine for 8 hours and from alcohol for 12 hours before visit.
• Patient accepts to turn stimulation off for 1 hour prior to the 3-month follow-up visit.
• Patient is willing to provide a written informed consent.
• Patient is available for the study visit, and other study requirements.

Exclusion Criteria:

• Cognitive impairment, or any characteristic that would limit study candidate's ability to complete study assessments, such as:

  • Active major psychiatric disorder (including clinically significant depression as rated by the clinician)
  • Patient had dementia interfering with their ability to co-operate or comply with study requirements or comprehend the informed consent (mini-mental exam score <24 or otherwise not capable of discernment)
  • Presence of an electrical or electromagnetic implant (e.g. cochlear implant, pacemaker)
  • Previous brain ablation/surgical procedure
  • Neurological injury, evidence of supraspinal central nervous system disease
  • History of seizures
  • Diathermy
  • Abuse of drugs or alcohol.
• Patient had botulinum toxin injection less than 6 months prior to enrollment
• Patient is participating in another clinical study that would confound data analysis.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the motor performance subscale of the Fahn Tolosa Marin Essential Tremor Rating Scale (FTM ETRS) score of target limb	The motor scale of the Fahn Tolosa Marin Essential Tremor Rating Scale (FTM ETRS) measures the maximum tremor severity in various body regions in different positions (rest, postural, kinetic). Each body area is evaluated in Part A of the FTM ETRS, which is composed of 10 questions. The FTM ETRS utilizes a 0 to 4 point scale where 0 indicates non-symptomatic (normal) and 4 indicates the most severe rating of the patient's tremor symptoms. The target limb (arm) will be identified at baseline for each patient as the limb most severely affected by tremors (highest score in postural or kinetic assessment in part A). The primary efficacy outcome is the mean percentage difference, 3 months post-implant, between the with and without stimulation states, as measured on the target limb identified at baseline, by the individual performance subscale score (i.e. postural or kinetic) on the FTM ETRS.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions of Adverse Events and Device Deficiencies observed	Proportions of the following events from DBS implant through study completion: Adverse Events:Surgery-relatedDevice-relatedTherapy-related; Device deficiencies	3 months
Change in total motor score on the Fahn Tolosa Marin Essential Tremor Rating Scale	The motor scale of the Fahn Tolosa Marin Essential Tremor Rating Scale (FTM ETRS) measures the maximum tremor severity in various body regions in different positions (rest, postural, kinetic). FTM ETRS is divided into 3 parts (A, B and C). The total motor score is calculated by summation of the individual scores to questions 1-15 of parts A and B. Maximum score of Part A is 88 points while that of Part B is of 36 points. The secondary efficacy OBJECTIVE is the mean difference between the with and without stimulation states, 3 months post-implant, as measured by the total motor score on the FTM ETRS. A high total motor score (i.e. close to 124) indicates overall poor motor performance - i.e. severe tremor. High difference value between total motor score measured with and without stimulation indicates a strong improvement.	3 months

Collaborators and Investigators

• Sponsor: Aleva Neurotherapeutics SA
• Investigators: Study Director: Alexandre Michalis, Aleva Neurotherapeutics SA

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2021
• Primary Completion (Actual): August 8, 2024
• Study Completion (Actual): August 8, 2024

Study Registration Dates

• First Submitted: July 5, 2022
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: CLI-12082

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