Neuropathic PainPSI-DBSNCT04279548
Posterior-superior Insula Deep Brain Stimulation in Refractory Peripheral Neuropathic Pain Patients
A study testing Deep Brain Stimulation in people with Neuropathic Pain and Neuropathy;Peripheral, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
This study evaluates the long term pain relief after deep brain stimulation on posterior-superior insula (PSI) in patients with refractory peripheral neuropathic pain who responded to real but not to sham non-invasive stimulation by deep repetitive transcranial magnetic stimulation - PSI-drTMS. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Neuropathic Pain, Neuropathy;Peripheral
- What is being tested?
- Deep Brain Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Jan 2018to 1 Jul 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and non-pregnant women aged 21-70 years.
- Ability to give informed consent in accordance with institutional policy.
- Have a diagnosis of neuropathic pain according to Douleur neuropathique 4 questions (DN4).
- Patients with predominant pain on the face and upper extremities in relation to the lower limbs. In this study, predominance will be defined as the difference of ≥ 30% or ≥ 2 points on the VAS scale between upper limb / face pain and lower limb pain.
- Pain lasting more than 12 months.
- Documented resistance to clinical treatment, defined in this study as persistence of pain after a minimum of 2 appropriate pharmacological treatments, including at least one antidepressant / anticonvulsant and / or gabapentins. Adequacy of treatments will be defined by the use of drugs in doses considered adequate in the literature or below the threshold of side effects.
Show all 10Show fewer
- Visual analog scale (EVA) scores of at least four during initial assessments.
- No change in the analgesic medication regimen for chronic neuropathic pain during the 4 weeks preceding entry into the study.
- Ability to comply with the tests and follow-up defined by the study protocol;
- Absence of routine contraindications to the surgical procedure (eg Coagulopathies, blood dyscrasias). These will be evaluated by members of the neurosurgical team responsible for the study
Who cannot join
- Alcohol abuse, medication, or addiction to illicit substances in the last 12 months.
- Diagnosis of idiopathic trigeminal neuralgia or atypical facial pain.
- Advanced cardiovascular disease stage that makes anesthesia and surgery unsafe, as determined by the neurosurgeon / clinical team.
- Clinically relevant lesions (tumor, for example) on preoperative magnetic resonance imaging.
- Cardiac pacemaker / implanted defibrillator or other active stimulators.
- Medical condition that requires repeated resonances.
Show all 17Show fewer
- Patients using chemotherapy for the treatment of malignant tumors or who need chronic oral or intravenous treatment with immunosuppressants or steroids.
- Patients unable to comply with the study visit schedule.
- Brain ablative surgery or previous neurosurgery that prevents or increases the risk of implantation of the electrodes.
- Patients of childbearing potential or infants with a positive pregnancy test or without the use of adequate contraception.
- Other medical conditions that require probable hospitalization during the study.
- History of epilepsy or status epilepticus.
- Chronic infection.
- Diagnosis of fibromyalgia.
- Plans for using diathermy in the future.
- Have any intracranial metal implant
- Current participation in another device investigation study or experimentation with drugs or surgery of any kind.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
São Paulo, 05403-900
About this study
This study evaluates the long term pain relief after deep brain stimulation on posterior-superior insula (PSI) in patients with refractory peripheral neuropathic pain who responded to real but not to sham non-invasive stimulation by deep repetitive transcranial magnetic stimulation - PSI-drTMS.
Read the detailed description
This study has two phases:
Study I) This study is an extension of 690.455/NCT01932905, in which non invasive stimulation of the posterior-superior insula (PSI) was performed by deep repetitive transcranial magnetic stimulation (drTMS) in patients with central neuropathic pain. Patients responding to active stimulation would be invited to join a phase II study aiming at the long term effects of drTMS by deep brain stimulation (DBS) of the PSI. The original 690.455/NCT01932905 study was negative concerning pain intensity reduction compared to sham stimulation, its main outcome. However, in this same study, active but not sham PSI stimulation provided significant anti-nociceptive effects, with anti-allodynic and anti-hyperalgesic properties.
This, and a number of experimental studies on peripheral neuropathic pain relief after PSI stimulation has lead us to perform an extension of the initial study, now including patients with refractory peripheral neuropathic pain to receive an induction series (5 consecutive daily stimulation sessions) of navigated PSI-deep rTMS against sham stimulation in a cross-over design. The calculate sample size for this cross-over screening study is 32. The primary endpoint is number of patients reaching significant pain relief (>50% pain intensity reduction assessed by visual analogue scale (VAS) ranging from 0: no pain, to 100mm:maximal pain imaginable) one week after the 5th stimulation session compared to baseline assessment. Other pain, quality of life and mood data were collected : pain interference with daily living (brief pain inventory), medication quantification score, neuropathic pain symptom inventory (NPSI).
In this screening trial, actual responders: patients refractory peripheral neuropathic pain with >50% pain intensity reduction after real but not sham PSI-drTMS will be offered the opportunity to join a subsequent PSI-DBS phase II trial.
Study II) In this phase, the PSI-DBS phase II trial (ethics review board number #690.455) will enroll 10 patients with refractory peripheral neuropathic pain from study 1 who responded to real but not to sham PSI-drTMS. Patients will have a stimulation electrode inserted neurosurgically by neuronavigation to the PSI, on the target used for drTMS, on the insula contralateral to the pain side.
After surgery, patients will be randomized to be in in either the ON or OFF DBS mode for three months, and then, after a flexible washout period, participants will be switched to the other corresponding mode (OFF or ON) for more three months. The study main outcome is number of responders (number of patients achieving >30% pain intensity reduction). Pain intensity will be measured on a 11-point visual numerical scale anchored at 0 (no pain) and 10 (maximal pain imaginable) and the score at the end of the three-month ON/OFF conditions will be compared to the respective baseline values in order too classify patients as responders or non-responders in each of the ON/OFF conditions. The main secondary outcome is safety, along with other clinical and general patients characteristics such as quality of life( QoL), mood, pain characteristics (McGill Pain Questionnaire-MPQ) and neuropathic pain symptom clusters (Neuropathic Pain Symptom Inventory).
After the ON/OFF double blinded period (main outcome) patients will be maintained for 3 months in the ON mode in a single blinded design, and then for more 6 months, maintained in the open phase of the study. This followup phase will allow us to gain insights into the potential long term effects of the treatment.
- Conditions
- Neuropathic Pain, Neuropathy;Peripheral
- Being tested
- Deep Brain Stimulation
- Keywords
- Deep Brain Stimulation
- Medical subject headings
- Neuralgia, Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep Brain StimulationDevice
Patients will have a stimulation electrode inserted neurosurgically by neuronavigation to the PSI, on the target used for drTMS, on the insula contralateral to the pain side. After surgery will be randomized to be in in either the ON or OFF DBS
| Study group | Role | What they receive |
|---|---|---|
| On DBS | Active comparator | Patients in the on mode DBS Receives: Device: Deep Brain Stimulation |
| Off DBS | Sham comparator | Patients in the off mode DBS Receives: Device: Deep Brain Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response (>30% pain intensity reduction) after ON but not OFF stimulation periods.
Pain intensity measured on a Numeric Rating Scale (0-10) where 0 is no pain and 10 is the worst pain imaginable
Measured: after 3 months in the ON / OFF conditions
Secondary outcomes (2)
% of patients with anxiety and depression
Assessment of the anxiety and depression by Hospital Anxiety And Depression Scale. The possible scores ranged from 0 to 21 for anxiety and depression. 0 to 7 could be regarded as being in the normal range, a score of 11 or higher indicating probable presence of the mood disorder and a score of 8 to 10 being just suggestive of the presence of the respective state.
Measured: baseline, 3 months and 15 months after the intervention
Incidence of symptoms of neuropathic pain
Symptoms of neuropathic pain evaluated by Neuropathic Pain Symptom Inventory
Measured: baseline, 3 months and 15 months after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start1 Jan 2018
- Primary completion1 Oct 2019
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Ciampi Araujo de Andrade, MD, PhD, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04279548
- Sponsor's protocol ID
- PSI-DBS
- Acronym
- PSI-DBS
- Status last verified
- Jan 2022
- First submitted
- 4 Feb 2020
- Last updated
- 28 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Participant data for primary and secondary outcome measures will be made available only when requested according with local ethics review recommendations
Publications
Dongyang L, Cunha PHM, Lapa JDS, Kubota GT, Junior JR, Fernandes AM, Thibes RB, Pinheiro DS, Iglesio RF, Duarte KP, Sato J, da Silva VA, Lucato LT, Figueiredo EG, Carlotti Junior CG, Yeng LT, Teixeira MJ, de Andrade DC. Insula Deep Brain Stimulation for Neuropathic Pain: A Cross-Over, Randomized, Sham-Controlled Trial. Neuromodulation. 2026 Apr;29(3):454-465. doi: 10.1016/j.neurom.2025.07.001. Epub 2025 Aug 18.
PubMed 40824225
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Posterior-superior Insula Deep Brain Stimulation in Refractory Peripheral Neuropathic Pain Patients
- ClinicalTrials.gov ID
- NCT04279548
- Acronym / sponsor ID
- PSI-DBS / PSI-DBS
- Conditions
- Neuropathic Pain, Neuropathy;Peripheral
- Keywords
- Deep Brain Stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 21 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the long term pain relief after deep brain stimulation on posterior-superior insula (PSI) in patients with refractory peripheral neuropathic pain who responded to real but not to sham non-invasive stimulation by deep repetitive transcranial magnetic stimulation - PSI-drTMS.
Detailed description
This study has two phases:
Study I) This study is an extension of 690.455/NCT01932905, in which non invasive stimulation of the posterior-superior insula (PSI) was performed by deep repetitive transcranial magnetic stimulation (drTMS) in patients with central neuropathic pain. Patients responding to active stimulation would be invited to join a phase II study aiming at the long term effects of drTMS by deep brain stimulation (DBS) of the PSI. The original 690.455/NCT01932905 study was negative concerning pain intensity reduction compared to sham stimulation, its main outcome. However, in this same study, active but not sham PSI stimulation provided significant anti-nociceptive effects, with anti-allodynic and anti-hyperalgesic properties.
This, and a number of experimental studies on peripheral neuropathic pain relief after PSI stimulation has lead us to perform an extension of the initial study, now including patients with refractory peripheral neuropathic pain to receive an induction series (5 consecutive daily stimulation sessions) of navigated PSI-deep rTMS against sham stimulation in a cross-over design. The calculate sample size for this cross-over screening study is 32. The primary endpoint is number of patients reaching significant pain relief (>50% pain intensity reduction assessed by visual analogue scale (VAS) ranging from 0: no pain, to 100mm:maximal pain imaginable) one week after the 5th stimulation session compared to baseline assessment. Other pain, quality of life and mood data were collected : pain interference with daily living (brief pain inventory), medication quantification score, neuropathic pain symptom inventory (NPSI).
In this screening trial, actual responders: patients refractory peripheral neuropathic pain with >50% pain intensity reduction after real but not sham PSI-drTMS will be offered the opportunity to join a subsequent PSI-DBS phase II trial.
Study II) In this phase, the PSI-DBS phase II trial (ethics review board number #690.455) will enroll 10 patients with refractory peripheral neuropathic pain from study 1 who responded to real but not to sham PSI-drTMS. Patients will have a stimulation electrode inserted neurosurgically by neuronavigation to the PSI, on the target used for drTMS, on the insula contralateral to the pain side.
After surgery, patients will be randomized to be in in either the ON or OFF DBS mode for three months, and then, after a flexible washout period, participants will be switched to the other corresponding mode (OFF or ON) for more three months. The study main outcome is number of responders (number of patients achieving >30% pain intensity reduction). Pain intensity will be measured on a 11-point visual numerical scale anchored at 0 (no pain) and 10 (maximal pain imaginable) and the score at the end of the three-month ON/OFF conditions will be compared to the respective baseline values in order too classify patients as responders or non-responders in each of the ON/OFF conditions. The main secondary outcome is safety, along with other clinical and general patients characteristics such as quality of life( QoL), mood, pain characteristics (McGill Pain Questionnaire-MPQ) and neuropathic pain symptom clusters (Neuropathic Pain Symptom Inventory).
After the ON/OFF double blinded period (main outcome) patients will be maintained for 3 months in the ON mode in a single blinded design, and then for more 6 months, maintained in the open phase of the study. This followup phase will allow us to gain insights into the potential long term effects of the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| On DBS | Active comparator | Device: Deep Brain StimulationPatients in the on mode DBS |
| Off DBS | Sham comparator | Device: Deep Brain StimulationPatients in the off mode DBS |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Men and non-pregnant women aged 21-70 years.
- Ability to give informed consent in accordance with institutional policy.
- Have a diagnosis of neuropathic pain according to Douleur neuropathique 4 questions (DN4).
- Patients with predominant pain on the face and upper extremities in relation to the lower limbs. In this study, predominance will be defined as the difference of ≥ 30% or ≥ 2 points on the VAS scale between upper limb / face pain and lower limb pain.
- Pain lasting more than 12 months.
Key exclusion criteria (17 listed)
- Alcohol abuse, medication, or addiction to illicit substances in the last 12 months.
- Diagnosis of idiopathic trigeminal neuralgia or atypical facial pain.
- Advanced cardiovascular disease stage that makes anesthesia and surgery unsafe, as determined by the neurosurgeon / clinical team.
- Clinically relevant lesions (tumor, for example) on preoperative magnetic resonance imaging.
- Cardiac pacemaker / implanted defibrillator or other active stimulators.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Deep Brain StimulationPatients will have a stimulation electrode inserted neurosurgically by neuronavigation to the PSI, on the target used for drTMS, on the insula contralateral to the pain side. After surgery will be randomized to be in in either the ON or OFF DBS | Device | Off DBS, On DBS |
Primary outcome
Response (>30% pain intensity reduction) after ON but not OFF stimulation periods.
Time frame: after 3 months in the ON / OFF conditions
Pain intensity measured on a Numeric Rating Scale (0-10) where 0 is no pain and 10 is the worst pain imaginable
2 secondary outcomes
% of patients with anxiety and depression
Time frame: baseline, 3 months and 15 months after the intervention
Incidence of symptoms of neuropathic pain
Time frame: baseline, 3 months and 15 months after the intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2022.
- Derived from this study: PubMed 40824225Dongyang L, Cunha PHM, Lapa JDS, Kubota GT, Junior JR, Fernandes AM, Thibes RB, Pinheiro DS, Iglesio RF, Duarte KP, Sato J, da Silva VA, Lucato LT, Figueiredo EG, Carlotti Junior CG, Yeng LT, Teixeira MJ, de Andrade DC. Insula Deep Brain Stimulation for Neuropathic Pain: A Cross-Over, Randomized, Sham-Controlled Trial. Neuromodulation. 2026 Apr;29(3):454-465. doi: 10.1016/j.neurom.2025.07.001. Epub 2025 Aug 18.
- Individual participant dataSharing planned: Yes. Participant data for primary and secondary outcome measures will be made available only when requested according with local ethics review recommendations
Related trials for Neuropathic Pain
Not yet recruiting
Pediatric Electrocutaneous Analgesia for Children Experiencing Neuropathic Pain
Neuropathic Pain, Chronic Pain
Active, not recruitingPhase 3
Evaluation of the Long-term Safety and Effectiveness of Suzetrigine (SUZ) in Participants With Painful Diabetic Peripheral Neuropathy (DPN)
Diabetic Peripheral Neuropathic Pain
Active, not recruiting
Comparative Effects of tDCS and tACS on Pain, Dexterity, and Strength in Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy (DPN)
Active, not recruitingPhase 1
A Phase 1b Study of BHV-7000 in Participants With Inherited Erythromelalgia
Familial Erythromelalgia
Recruiting
Post Operative Pain and Vagal Stimulation
Rectal Surgery, Pain (Visceral, Somatic, or Neuropathic)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep Brain Stimulation in people with Neuropathic Pain and Neuropathy;Peripheral, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response (>30% pain intensity reduction) after ON but not OFF stimulation periods. (time frame: after 3 months in the ON / OFF conditions). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04279548, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2022.