Thalamic-Burst-DBS for Neuropathic Pain

NCT ID: NCT05204472

Last Updated: 2024-10-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2027-02-28

Brief Summary

Central post-stroke pain (CPSP) is a neuropathic pain syndrome and one of the major sequelae after ischemic or hemorrhagic cerebral stroke.

Recently, a modified stimulation paradigm has been developed in the field of spinal cord stimulation (SCS) for a variety of neuropathic pain disorders. To date, this stimulation paradigm has not yet been evaluated systematically for deep brain stimulation to treat neuropathic pain disorders.

The purpose of this clinical investigation is to investigate if Burst-DBS of the thalamus is more effective compared to classical continuous low-frequency stimulation DBS to reduce the subjective pain intensity in patients with chronic neuropathic pain after stroke or in patients with neuropathic facial pain.

Detailed Description

Central post-stroke pain (CPSP) is a neuropathic pain syndrome and one of the major sequelae after ischemic or hemorrhagic cerebral stroke. Neuropathic facial pain (NFP) can arise after damage to or affection of the trigeminal nerve caused by trauma, infection or postsurgery and results in characteristic burning and shooting pain of the affected area in the face.

The lack of effective analgesic treatment for these two conditions continues to be an unmet medical need and led to the investigation of alternative treatments of CPSP and NFP such as deep brain stimulation (DBS). DBS is an invasive neuromodulation therapy that consists of placing small electrodes into confined anatomical structures of the brain to deliver small therapeutic currents.

Recently, a modified stimulation paradigm has been developed in the field of spinal cord stimulation (SCS) for a variety of neuropathic pain disorders. This so-called burst stimulation provides pulse trains of five high-frequency pulses at 500 Hz (= 500 Hz spike frequency) occurring 40 times a second (= 40 Hz burst frequency). Burst SCS has been demonstrated to provide a better pain relief compared to classical tonic (continuous application of 50 Hz stimulation) SCS without causing paresthesia. To date, this stimulation paradigm has not yet been evaluated systematically for deep brain stimulation to treat neuropathic pain disorders.

The purpose of this clinical investigation is to investigate if Burst-DBS of the thalamus is more effective compared to classical continuous low-frequency stimulation DBS to reduce the subjective pain intensity in patients with chronic neuropathic pain after stroke or in patients with neuropathic facial pain.

Conditions

Central Post-stroke Pain; Neuropathic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Burst DBS first, Tonic DBS second

10 days of Burst-stimulation followed by 10 days of active tonic stimulation (Burst-DBS -\> tonic-DBS)

Group Type: EXPERIMENTAL

Burst DBS

Intervention Type: DEVICE

Patients undergo stereotactic implantation of DBS electrodes in the thalamus under local anesthesia. The DBS electrodes will be connected to an external pacemaker for a time period of four weeks. On the first day following surgery, patients will undergo an empirical clinical testing of the stimulation parameter settings. At the same day patients will undergo somatosensory- and contact heat-evoked potential recording for phenotype-stratification (post-hoc analysis).During the next 24 days with the electrodes externalized and connected to the external pacemaker, patients will be randomly assigned in a 1:1 ratio to one of the two groups that undergo two blocks of stimulation:

12 days of of Burst-stimulation followed by 12 days active tonic stimulation (Burst-DBS -> tonic-DBS) Between each stimulation block the stimulator will be switched off for one day to prevent any hang-over effects of stimulation (wash-out period).

Tonic DBS

Intervention Type: DEVICE

Patients undergo stereotactic implantation of DBS electrodes in the thalamus under local anesthesia. The DBS electrodes will be connected to an external pacemaker for a time period of four weeks. On the first day following surgery, patients will undergo an empirical clinical testing of the stimulation parameter settings. At the same day patients will undergo somatosensory- and contact heat-evoked potential recording for phenotype-stratification (post-hoc analysis).During the next 24 days with the electrodes externalized and connected to the external pacemaker, patients will be randomly assigned in a 1:1 ratio to one of the two groups that undergo two blocks of stimulation:

12 days of active tonic stimulation followed by 12 days of Burst-stimulation (tonic-DBS -> Burst-DBS) Between each stimulation block the stimulator will be switched off for one day to prevent any hang-over effects of stimulation (wash-out period).

Tonic DBS first, Burst DBS second

10 days of active tonic stimulation followed by 10 days of Burst-stimulation (tonic-DBS -\> Burst-DBS)

Group Type: ACTIVE_COMPARATOR

Burst DBS

Intervention Type: DEVICE

Patients undergo stereotactic implantation of DBS electrodes in the thalamus under local anesthesia. The DBS electrodes will be connected to an external pacemaker for a time period of four weeks. On the first day following surgery, patients will undergo an empirical clinical testing of the stimulation parameter settings. At the same day patients will undergo somatosensory- and contact heat-evoked potential recording for phenotype-stratification (post-hoc analysis).During the next 24 days with the electrodes externalized and connected to the external pacemaker, patients will be randomly assigned in a 1:1 ratio to one of the two groups that undergo two blocks of stimulation:

12 days of of Burst-stimulation followed by 12 days active tonic stimulation (Burst-DBS -> tonic-DBS) Between each stimulation block the stimulator will be switched off for one day to prevent any hang-over effects of stimulation (wash-out period).

Tonic DBS

Intervention Type: DEVICE

Patients undergo stereotactic implantation of DBS electrodes in the thalamus under local anesthesia. The DBS electrodes will be connected to an external pacemaker for a time period of four weeks. On the first day following surgery, patients will undergo an empirical clinical testing of the stimulation parameter settings. At the same day patients will undergo somatosensory- and contact heat-evoked potential recording for phenotype-stratification (post-hoc analysis).During the next 24 days with the electrodes externalized and connected to the external pacemaker, patients will be randomly assigned in a 1:1 ratio to one of the two groups that undergo two blocks of stimulation:

12 days of active tonic stimulation followed by 12 days of Burst-stimulation (tonic-DBS -> Burst-DBS) Between each stimulation block the stimulator will be switched off for one day to prevent any hang-over effects of stimulation (wash-out period).

Interventions

Burst DBS

Patients undergo stereotactic implantation of DBS electrodes in the thalamus under local anesthesia. The DBS electrodes will be connected to an external pacemaker for a time period of four weeks. On the first day following surgery, patients will undergo an empirical clinical testing of the stimulation parameter settings. At the same day patients will undergo somatosensory- and contact heat-evoked potential recording for phenotype-stratification (post-hoc analysis).During the next 24 days with the electrodes externalized and connected to the external pacemaker, patients will be randomly assigned in a 1:1 ratio to one of the two groups that undergo two blocks of stimulation:

12 days of of Burst-stimulation followed by 12 days active tonic stimulation (Burst-DBS -> tonic-DBS) Between each stimulation block the stimulator will be switched off for one day to prevent any hang-over effects of stimulation (wash-out period).

Intervention Type: DEVICE

Tonic DBS

Patients undergo stereotactic implantation of DBS electrodes in the thalamus under local anesthesia. The DBS electrodes will be connected to an external pacemaker for a time period of four weeks. On the first day following surgery, patients will undergo an empirical clinical testing of the stimulation parameter settings. At the same day patients will undergo somatosensory- and contact heat-evoked potential recording for phenotype-stratification (post-hoc analysis).During the next 24 days with the electrodes externalized and connected to the external pacemaker, patients will be randomly assigned in a 1:1 ratio to one of the two groups that undergo two blocks of stimulation:

12 days of active tonic stimulation followed by 12 days of Burst-stimulation (tonic-DBS -> Burst-DBS) Between each stimulation block the stimulator will be switched off for one day to prevent any hang-over effects of stimulation (wash-out period).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Signed informed consent
• Age 18-75 years
• Patients suffering from chronic (duration > 12 months) unilateral neuropathic pain caused by an ischemic or haemorrhagic cerebral stroke or
• Patients suffering from chronic (duration > 12 months) unilateral neuropathic facial pain due to one of the following causes:

1. post-herpes-zoster-neuralgia,

2. posttraumatic, neuropathic facial pain,

3. atypical trigeminal neuralgia after surgical intervention

• Severe baseline pain intensity (VAS score > 6/10) considered as resistant to medication specific to neuropathic pain at sufficient doses and durations (including at least antiepileptics and antidepressants)

Exclusion Criteria

• Significant cognitive impairment (total MOCA score < 1.5 standard deviations from age- and education adapted mean values),
• DSMIV axis I or II psychiatric disorder
• Relevant psychosocial risk factors (any of): history of other chronic pain syndrome, pain catastrophizing, substance abuse, secondary gain
• Contra-indication to surgery, anesthesia, or MRI
• Known or suspected non-compliance or inability to operate the DBS system
• Woman with childbearing potential
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia. etc. of the subject
• Participation in another interventional clinical trial within 30 days prior to this trial or during the trial
• Previous enrollment into the current trial
• Enrolment of the investigator's family members, employees, and other dependent persons
• Patients who are planned to undergo diathermy, electroshock therapy or transcranial magnetic stimulation (TMS)
• Patients with implanted electric devices (i.e. cardiac defibrillator, pacemaker)
• Patients who are at poor surgical risk (i.e. patients with multiple severe illnesses or active general infections)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andreas Nowacki, MD

Role: PRINCIPAL_INVESTIGATOR

Insel Gruppe AG, University Hospital Bern

Locations

Dep. of Neurosurgery, Bern University Hospital

Bern, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Andreas Nowacki, MD

Role: CONTACT

andreas.nowacki@insel.ch

+41 31 6320014

Söll Nicole

Role: CONTACT

nicole.soell@insel.ch

+41316323164

Facility Contacts

Andreas Nowacki, MD

Role: primary

andreas.nowacki@insel.ch

+41 31 632 2409

Claudio Pollo, MD

Role: backup

claudio.pollo@insel.ch

+41 31 632 2409

Other Identifiers

DBS for neuropathic pain

Identifier Type: -

Identifier Source: org_study_id