Thalamic-Burst-DBS for Neuropathic Pain

Neuropathic Pain Clinical Trial

Official title:

Burst-Deep Brain Stimulation of the Thalamus for Neuropathic Facial Pain and Central Poststroke Pain: a Prospective, Randomized Cross-over Feasibility Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05204472
• Other study ID #: DBS for neuropathic pain
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: February 2027

Study information

• Verified date: October 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Andreas Nowacki, MD
• Phone: +41 31 6320014
• Email: andreas.nowacki[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 2027
• Est. primary completion date: August 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Neuralgia
• Neuropathic Pain

Intervention

Device:
• 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).
• 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).

Locations

Country	Name	City	State
Switzerland	Dep. of Neurosurgery, Bern University Hospital	Bern

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage reduction of pain intensity	Percentage reduction of pain intensity on the numeric rating scale (NRS 1-10) after each stimulation-block compared to the baseline pain intensity before surgery. Score 0-10 with 0 representing no pain, and 10 maximum pain intensity	1 week after surgery
Primary	Percentage reduction of pain intensity	Percentage reduction of pain intensity on the numeric rating scale (NRS 1-10) after each stimulation-block compared to the baseline pain intensity before surgery. Score 0-10 with 0 representing no pain, and 10 maximum pain intensity	2 weeks after surgery
Secondary	Change of pain intensity on the numeric rating scale	Efficacy of DBS after 12 months of open-label stimulation measured as the percentage change of pain intensity on the numeric rating scale compared to baseline. Score 0-10 with 0 representing no pain, and 10 maximum pain intensity	12 months after surgery
Secondary	Percentage change of pain intensity on the Neuropathy pain scale	Efficacy of DBS after 12 months of open-label measured as the percentage change of pain intensity on the Neuropathy pain scale (DN-4) compared to baseline. Score 0-10 with 0 representing no pain, and 100 maximum pain intensity	12 months after surgery
Secondary	Percentage improvement of quality of life measured by the EuroQoL 5D-5L	Efficacy of DBS after 12 months of open-label measured as the percentage improvement of quality of life measured by the EuroQoL 5D-5L questionnaire (Mobility, Self-Care, Usual Activities, Pain/Discomfort, Anxiety/ Depression (rating from no problems to extreme problems) and health status self rating by patient (Score 0-100, 0 the worst health and 100 the best health)) compared to baseline.	12 months after surgery
Secondary	Change of dosage of analgesic medication(s)	Change of dosage of analgesic medication(s) at 12 months of open-label stimulation measured as the total dosage in mg per medication per day with reference to baseline	12 months after surgery
Secondary	Efficacy of DBS	Efficacy of DBS after 12 months of open-label stimulation measured as the percentage improvement of depressive symptoms by the BDI questionnaire compared to baseline	12 months after surgery