Effects of Microelectrode-based Brain Stimulation in Humans (HDBS)

The currently available treatments of Parkinson's disease (PD) and Essential Tremor (ET) are inadequate and accompanied by adverse side effects making the treatment much less effective. This includes treatments with pharmaceuticals as well as electrical brain stimulation (DBS; Deep Brain Stimulation). To address this challenge, we have systematically worked to identify and overcome the shortcomings with current brain stimulation. Essential has been to achieve an understanding of the mechanisms behind the ubiquitous tissue reactions (often referred to as "foreign body reactions"), with loss of nerve cells near implanted electrodes and how to accomplish minimal tissue reactions/damage, which is necessary to enable therapeutically efficient low-intensity stimulation at precise locations. A further challenge relates to individual differences at the level of neuronal networks, making the exact sites in the brain that cause therapeutic and adverse side effects when stimulated not known in advance and thus requiring individual determination. Our strategy has therefore been to develop highly biocompatible microelectrodes (thinner than a human hair and highly flexible) and a guiding investigational device for controlled insertion of a cluster of such microelectrodes in deep target tissue. This enables individualized selection of appropriate stimulation sites. This technique, termed by us "High Definition Brain Stimulation" (HDBS), proved remarkably successful in animal models of both Parkinson's disease and pain by reliably providing powerful symptom relief without noticeable adverse side effects. For this first in human (FIH) investigation of microelectrode-based brain stimulation, we have systematically minimized all identified and foreseeable risks through optimization of the microelectrodes, the design of the investigational device for HDBS and development of simple minimally invasive surgical insertion methods. Extensive monitored safety tests in animals have confirmed the picture of negligeable tissue reactions/damage and absence of bleeding in the target area. Biological safety is also ensured by using only well-established materials documented for chronic implantation in the brain, established sterilization methods, identified safe stimulation intensities, and that the insertion procedures are adapted to well-established precision neurosurgical instruments and routines. The study is an early (FIH) feasibility clinical investigation which will be conducted in up to 12 patients with Parkinson's disease and/or Essential Tremor who are already scheduled for implantation of established DBS. The HDBS device will be inserted into awake patients in the same track as planned for the established DBS electrode. The evaluation will follow a protocol that includes stimulation of predetermined subsets of microelectrodes at up to 4 predetermined levels (depth) in the brain. The stimulation intensity for each subgroup is gradually increased until either a therapeutic effect or an undesirable side effect has been achieved. If an unacceptable effect is elicited, stimulation is immediately interrupted and a new subset of electrodes will be tested. After completion of the evaluation, the HDBS cluster electrode is removed and the implantation of an established permanent DBS electrode is completed. The evaluation will take up to 2.5 hours per patient. The patient's verbal responses, gestures, changes (if any) in tremors, rigidity, speech ability (such as slurring) or facial expressions before, during and after stimulation will be linked to the stimulation parameters (stimulation intensity, subgroup of microelectrodes, depth in the brain and time of reaction) and documented in writing and through video recordings. The analysis will only be made on anonymized data. The primary objective of this early feasibility, FIH, clinical investigation is to clarify whether HDBS (High Definition Brain Stimulation), through individualized stimulation of appropriate subgroups of implanted biocompatible microelectrodes, can provide a powerful therapeutic effect with minimal negative side effects also in humans. In addition, it is intended to simultaneously obtain important information that can be used by the neurosurgeon to improve the subsequent placement of the already scheduled permanent DBS electrode in the individual patient and thereby improve the treatment. Consequently, the secondary objective is to clarify whether HDBS can be used by the neurosurgeon to improve the placement of a permanent DBS electrode. The project paves the way for permanent HDBS with completely new opportunities for powerful, sustainable therapy with minimal side-effects in Parkinson's disease, Essential Tremor and other intractable neurologic disorders. Moreover, the HDBS technology enables new and potent opportunities for brain research.

Study Overview

• Status: Not yet recruiting
• Conditions: Essential Tremor; Parkinsons Disease (PD)
• Intervention / Treatment: Device: High Definition Brain Stimulation (HDBS)

Detailed Description

The primary objective of this early feasibility clinical investigation is reached if any of the tested subgroups/sites enable powerful therapeutic effects with minimal adverse effects in a patient. A continuous assessment is made as data from different patients accumulate over time to enable an estimation of the success rate.

To address the secondary objective, areas from which appropriate effects are elicited are marked with green and inappropriate areas are marked with red on the last page of the Case Report Form (CRF) for each stimulation depth to provide an overview of the results for each individual patient. This is compared to results obtained from the subsequent evaluation of different contacts on the permanent DBS 3-8 weeks after surgery to assess to what extent the mapping using HDBS can predict DBS outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jens Schouenborg, PhD; Phone Number: +46702924572; Email: jens.schouenborg@med.lu.se
• Study Contact Backup: Name: Hjalmar Bjartmarz, MD; Phone Number: +46705343055; Email: hjalmar.bjartmarz@skane.se

Study Locations

• Sweden
  • Skåne County
    • Lund, Skåne County, Sweden, SE-12185
      • Skåne University Hospital
      • Contact: Hjalmar Bjartmarz, MD; Phone Number: +46705343055; Email: hjalmar.bjartmarz@skane.se
      • Contact: Hakan Widner, MD; Phone Number: +4646171000; Email: hakan.widner@skane.se
      • Principal Investigator: Hjalmar Bjartmartz, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The target population for the clinical device to be investigated are adult patients with Parkinson's disease or essential tremor that are already scheduled for permanent implantation of devices for deep brain stimulation. This implies that these patients are an already selected group of patients deemed to be appropriate patients for DBS.
• Patients that are fully capable of understanding the patient information.
• Patients that accept to be awake during the investigation
• Patients that accept to be video-filmed during the investigation.

Exclusion Criteria:

• Patients that do not accept to be awake during the stimulation procedure.
• Patients for which the intended extension of surgery time (up to 2,5 hours) is considered by the neurosurgeon to be an unacceptable risk.
• Patients with a known history of blood clotting disorder.
• Patients with a known history of bleeding disorder.
• Patients under age 18.
• Pregnant women and women that are breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: High Definition Brain Stimulation; The investigational device, comprising multiple microelectrodes, will be stereotactically inserted into the brain of awake patients in the same track as planned for the established Deep Brain Stimulation (DBS) electrode.

Device: High Definition Brain Stimulation (HDBS); The investigational device will be inserted into the brain of awake patients in the same track as planned for the established Deep Brain Stimulation (DBS) electrode. The evaluation will follow a protocol that includes stimulation of predetermined subsets of microelectrodes at up to 4 predetermined levels (depth) in the brain. The stimulation intensity for each subgroup is gradually increased until either a therapeutic effect or an undesirable side effect has been achieved. If an unacceptable effect is elicited, stimulation is immediately interrupted and a new subset of electrodes is tested. After completion of the evaluation, the investigational device will be removed and the implantation of an established permanent DBS electrode is completed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in motor performance during microelectrode based deep brain stimulation	Primary outcome measure is, for each combination of stimulation sites (i.e. subgroup of stimulated microelectrodes), an aggregated outcome measure based on the following components: symptom relief using the clinically established instruments Unified Parkinson Disease Rating Scale (UPDRS, item III) for patients with Parkinson's disease (PD) symptoms: tremor and rigidity and Essential Tremor Rating Scale (ETRS) for patients with Essential tremor; both instruments use a scale from 0 to 4; a lower score is better and; unwanted side effects such as verbal responses, gestures, slurring of speech, dystonia or facial expressions are scored as zero (0), mild (1), moderate (2) and severe (3) for which the worst unwanted side effect measured is used in the aggregated outcome measure. For each combination of stimulation sites, the (aggregated) primary outcome measure is either 1 or 0, depending on whether or not a powerful therapeutic effect with minimal unwanted side effects is reached.	2.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate	• Number of patients, expressed as percentage of all tested patients, for which it was possible to substantially reduce recorded symptoms with minimal unwanted side effects.	2.5 hours
Thresholds for beneficial effects	If possible, for each combination of stimulation sites, a threshold expressed in micro-Amps per pulse for at least one of the following effects will be documented: 1) beneficial effects on one symptom, and 2) potent relief of one symptom. If no beneficial effect/potent relief is achieved for a particular combination of stimulation sites this will also be documented.	2.5 hours
Aggravation of already existing symptoms	Unwanted side effects, consisting in aggravation of existing symptoms by the stimulation. These include increased tremor estimated using ETRS for patients with Essential tremor and worsened PD symptoms (tremor and rigidity) rated using the UPDRS (item III) instrument. Both instruments use a scale from 0 to 4 where a lower score is better. These outcome measures are documented together with stimulation intensity (in micro-Amps) and respective subgroup of microelectrodes used.	2.5 hours
Other unwanted side effects for PD and ET patients:	Other unwanted side effects than aggravated PD/ET symptoms, such as verbal responses, gestures, slurring of speech, dystonia or facial expressions are documented and scored as zero (score=0), mild (score=1), moderate (score=2) and severe (score=3). These outcome measures of unwanted side-effects are documented together with stimulation intensity (in micro-Amps), respective subgroup of microelectrodes used (i.e. the stimulated brain sites).	2.5 hours
Effects of DBS	Recordings of therapeutic and unwanted side effects caused by stimulation of each of the different contacts on the implanted established DBS electrodes 3-8 weeks after surgery.	8 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other observations	Explorative outcomes: Other observations, such as patient-reported effects on perception, thoughts, emotions during the evaluation, will be documented.	2.5 hours

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Skane University Hospital
• Investigators: Study Director: Jens Schouenborg, PhD, Lund University, Lund, Sweden

Publications and helpful links

General Publications

• Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Van Hilten JJ, LaPelle N. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan. Mov Disord. 2007 Jan;22(1):41-7. doi: 10.1002/mds.21198.
• Fahn S, Tolosa E, Marin C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders. 2nd ed. Baltimore, MD: Williams & Wilkins; 1993:225-234.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: August 24, 2026
• First Submitted That Met QC Criteria: September 9, 2026
• First Posted (Actual): September 15, 2026

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Essential Tremor; Parkinson's disease; First in human feasibility study; Microelectrode based deep brain stimulation
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Essential Tremor
• Other Study ID Numbers: CIV-ID 25-10-054717

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Summary data will be made available via ClinicalTrials.gov within 1 year of the study's conclusion.

Individual participant data underlying the results in a publication will be anonymized and will be available with a publication to the extent that they do not allow identification of individual participants. The study is a first in human early feasibility investigation with a small number of participants. This means that only limited individual data can be shared without identifying participants.

• IPD Sharing Time Frame: Summary data will be made available via ClinicalTrials.gov within 1 year of the study's conclusion

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No