Chronic Outcome Monitoring for DBS in Dystonia

ConditionDystonia

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age5-80

SponsorCharite University, Berlin, Germany

About this trial

Dystonia is a severe movement disorder involving increased muscular activity and can be very variable. To date, the treatment of dystonia is challenging. One effective therapy is deep brain stimulation (DBS), an invasive therapy, where stimulation electrodes are inserted in deep brain regions and a continuous electrical therapy is delivered via a pacemaker. However, the optimization of the therapy is a long process, up to months and there is no immediate adaptation to different disease states.

This project aims to improve DBS therapy: The first aim is to learn more about electrical brain activity that could be the feedback signal for individualized therapy. Secondly, the investigators want to gather information about the long-term development of the signal and potential hints for optimal therapy locations that could be acutely used to accelerate therapy optimization. To date, recordings mainly in lab settings, have suggested low-frequency activity as a biomarker for dystonia. Biomarkers are signals that are changed with therapy and that reflect symptom severity. Further understanding of the low-frequency biomarker for dystonia and its applicability in everyday life is one of the objectives in this study. Therefore, using a pacemaker that can also record brain activity, biomarker activity will be recorded for 12 months. At the same time, development of clinical symptoms will be assessed using an application with weekly questionnaires on symptoms and a video diary. At monthly appointments for data saving, resting state as well as motor activity during a finger tapping task will be recorded to also assess the development of side-effects, such as stimulation-induced slowing, and their biomarkers.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Ability to give informed consent for the study, or in pediatric patients, legal guardian or parent willing to give informed consent

Diagnosis of dystonia, which may be isolated or generalized

Wish to receive surgical intervention with DBS to the internal pallidal globe (GPi)

Decision to receive the sensing-enabled neurostimulator (Percept neurostimulator) PC/RC

Disqualifiers

Severe psychiatric disorders (BDI>20)

Other severe medical conditions, that may interfere with the successful paritcipation in the study protocol

No consent given

Trial population

All patients with dystonia who receive pallidal deep brain stimulation with the Percept IPG in the study centers are offered to participate in the study. Since dystonia is a variable condition that might also affect young patients, also children and youths will, together with their parents/legal guardians, be informed about the study and consented as possible.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

Not listed

Trial groups

No trial groups listed

Trial outcomes

Primary outcomes

Amount of low-frequency band oscillatory suppression

Local field potential recordings of pallidal neuronal activity will be recorded using the Percept neurostimulator. On the one hand, automatically preprocessed peak-biomarker activty in the low-frequency range (7.8-12 Hz) will be recorded continuously using the Chronic BrainSense function of the Percept neurostimulator for one year at a temporal resolution of 1 sample/10 min. Over time and with optimization of clinical DBS settings, low frequency dynamics will change in correlation with symptom improvement. On the other hand, at monthly recordings, local field potentials at a sampling frequency of 250 Hz will be recorded ON and OFF stimulation at various intensities up to the therapeutic stimulation intensity. After preprocessing and transformation to the time-frequency domain, low frequency activity will be compared between different therapy settings.

Time frame

monthly recordings for 12 months

Proportion of pathological increase in beta band oscillatory activity

Local field potential recordings of pallidal neuronal activity will be recorded using the Percept neurostimulator. On the one hand, automatically preprocessed peak-biomarker activity in the beta band (13-35 Hz) will be recorded continuously using the Chronic BrainSense function of the Percept neurostimulator for one year at a temporal resolution of 1 sample/10 min. Over time and with chronic DBS settings, beta band activity will increase in correlation with development of bradykinesia. On the other hand, at monthly recordings, local field potentials at a sampling frequency of 250 Hz will be recorded ON and OFF stimulation at various intensities up to the therapeutic stimulation intensity. After preprocessing and transformation to the time-frequency domain, beta band activity will be compared between different therapy settings.

Time frame

monthly recordings for 12 months

Secondary outcomes

Proportion of dystonic symptom improvement in patient reported outcomes

Weekly patient reported outcomes focused on motor symptoms (4 items: general movement, walking, use of hands, neck muscle tenseness) will provide insights into subjective evaluation of participants, on a 9-points likert scale. Lower scores imply improved symptoms.

Time frame

weekly, through study completion, up to 12 months

Proportion of dystonic symptom improvement in kinematic video-based analysis

Based on weekly video recordings or at least monthly recordings at the lab visits, automated models will be used to assess symptom severity. With DBS optimization, an improvement of symptom severity is expected, that can be objectified in video kinematics as angle of deviation from midline, smaller angles imply reduced deviation and symptom improvement.

Time frame

weekly, through study completion, for up to 12 months

Proportion of dystonic symptom improvement based on validated scales - Burke Fahn Marsden Dystonia Rating Scale

At the monthly recordings, trained clinicians and movement disorder specialists will assess the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), lower scores indicate symptom improvement.

Time frame

monthly, through study completion, for up to 12 months

Proportion of dystonic symptom improvement based on validated scales - Toronto Western Spasmodic Torticollis Rating Scale

At the monthly recordings, trained clinicians and movement disorder specialists will assess Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in patients with cervical dystonia, lower scores indicate symptom improvement.

Time frame

monthly, through study completion, for up to 12 months

Other outcomes

Unified Parkinson's Disease Rating Scale

At the first recording (post-operatively) and the last recording (12 months post-surgery) the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) is assessed. We expect a stimulation-induced increase (deterioration) of the UPDRS-III.

Time frame

at beginning and completion of the study, up to 12 months

Beck's Depression Inventory

At the first recording (post-operatively) and the last recording (12 months post-surgery) the Beck's Depression Inventory-II (BDI-II) is assessed. We expect a stimulation-associated reduction (=improvement) of the BDI-II.

Time frame

at beginning and end of study, up to 12 months

Apathy Scale

At the first recording (post-operatively) and the last recording (12 months post-surgery) the Starkstein Apathy Scale is assessed. We expect a stimulation-induced improvement of the Starkstein Apathy Scale.

Time frame

at beginning and end of study, up to 12 months

Obsessive-Compulsive Symptoms

At the first recording (post-operatively) and the last recording (12 months post-surgery) the Obsessive Compulsive Inventory (OCI) is assessed. We expect a stimulation-induced improvement of the OCI.

Time frame

at beginning and end of study, up to 12 months