Neuropathic PainNCT05168319
Effects and Mechanism of Prolonged Continuous Theta Burst Stimulation on Neuropathic Pain
A study testing Repetitive transcranial magnetic stimulation in people with Neuropathic Pain and Repetitive Transcranial Magnetic Stimulation, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
Neuropathic pain (NP) is one type of refractory chronic pain condition,medical treatments for NP is limited because of its poorly response. A noninvasive brain-stimulation method called transcranial magnetic stimulation (TMS) has garnered interest as an alternative treatment for intractable NP potentially through… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Neuropathic Pain, Repetitive Transcranial Magnetic Stimulation
- What is being tested?
- Repetitive transcranial magnetic stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 94 participants
- Where
- 1 siteChina
- Study dates
- 28 Feb 2022to 30 Jan 2023
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (1)woman or man over 18 and under 70 years old; （2）pain fulfilling the criteria for probable or definite peripheral neuropathic pain ; (3) pain for at least 3 months, continuous pain (at least four days per week), at least moderate intensity (≥ 4/10 assessed by VAS) ; (4) stable pharmacological treatment for pain at least 2 weeks before inclusion; (5) able to cooperate in completing questionnaire.
Who cannot join
- (1) Any clinically significant or unstable ongoing medical or psychiatric disorder including major depression; (2) History of substance abuse (alcohol, drugs); (3) Past treatment with repetitive transcranial magnetic stimulation (rTMS); (4) Contraindications to rTMS (previous severe head trauma or neurosurgical intervention, past or current epilepsy, active brain tumor, intracranial hypertension, implanted ferromagnetic devices, e.g., cardiac pacemaker, neurostimulator, or cochlear implants); (5) other type of pain more severe than neuropathic pain; (6) Any difficulty to fill out questionnaires (due to language or cognitive problems); (7) impossibility to be followed during the time course of the study;
Trial locations and contacts
1 site in 1 country.
China1 site
The second affiliated hospital of Zhejiang University hangzhou
Hangzhou, Zhejiang
About this study
Neuropathic pain (NP) is one type of refractory chronic pain condition,medical treatments for NP is limited because of its poorly response. A noninvasive brain-stimulation method called transcranial magnetic stimulation (TMS) has garnered interest as an alternative treatment for intractable NP potentially through inducing therapeutic brain plasticity.Indeed, high-frequency (≥ 5 Hz) Repetitive TMS (rTMS) over the primary motor cortex (M1) is suggested to be able to reduce neuropathic pain in randomized controlled studies.Overall, the clinical application of rTMS in chronic pain is still limited by the response rate,the investigation of rTMS protocols is important for improving rTMS analgesia. Theta burst stimulation (TBS) mimics the bursts of neuronal firing which results in robust long-term potentiation. Continuous TBS (cTBS) is designed to decrease excitability, whereby prolonged cTBS (pcTBS, i.e. multiple cTBS being delivered continuously) has recently been demonstrated to increase excitability. More importantly, pcTBS was found to have comparable or even better analgesic effects than standard 10 Hz rTMS. These findings together call for more studies to validate the analgesic efficacy of pcTBS.
In this study, the investigators aim to assess and compare the efficacy of prolonged continuous theta burst stimulation (pcTBS) with 10HZ rTMS in NP patients.
Read the detailed description
The investigators designed a randomized, double-blind, sham-controlled study at 1 center. fifty NP patients were randomly assigned to 3 groups. A series of 5 daily pcTBS(1200 pulses/session) or 10-Hz rTMS (1500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patients.
- Being tested
- Repetitive transcranial magnetic stimulation, Sham stimulation
- Medical subject headings
- Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive transcranial magnetic stimulationDevice
Participants received 10HZ rTMS protocol consisted of 5 sessions over 5 consecutive workdays
Repetitive transcranial magnetic stimulationDevice
Participants received pcTBS protocol consisted of 5 sessions over 5 consecutive workdays
Sham stimulationDevice
Participants received Sham rTMS stimulations consisted of 5 sessions over 5 consecutive workdays
| Study group | Role | What they receive |
|---|---|---|
| pcTBS | Experimental | pcTBS was administered to the left M1 at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline. Receives: Device: Repetitive transcranial magnetic stimulation |
| 10HZ rTMS | Active comparator | The rTMS protocol included 15 trains of 10-second stimulation given at 10 Hz to the left M1 at 80% resting motor threshold (RMT), with the inter-train interval being set to 50 seconds (1500 pulses) Receives: Device: Repetitive transcranial magnetic stimulation |
| Sham | Sham comparator | The Sham stimulation was delivered using the same protocol, with the coil being orientated at 90° to the scalp so that the magnetic field would be delivered away from the scal Receives: Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The mean change from baseline in pain intensity measured with the visual-analogic scale (VAS)
The primary outcome measure was the mean change from baseline over the course of 5 (group by time interaction) in average pain intensity measured with the visual-analogic scale (VAS) ( 0= no pain and 10= maximal pain). Baseline average pain intensity was assessed at inclusion then on the day of randomization, just before the first rTMS session (day 1) and corresponded to the average of these two values.
Measured: through study completion, an average of 8 months
Secondary outcomes (7)
Motor-evoked potential (MEP)
Corticospinal excitability was measured with MEP at rest of the first dorsal interosseous (FDI) muscle, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward).
Measured: through study completion, an average of 8 months
Cortical silent period (CSP)
Corticospinal excitability was measured with CSP during a sustained voluntary FDI muscle contraction, A total of 20 single pulses were consecutively delivered to the hand region of the left M1 at 120% RMT (45° to the midline, handle pointing backward).
Measured: through study completion, an average of 8 months
The sensory dimension of pain and affective dimension of pain
The sensory dimension of pain (rated on 33) and affective dimension of pain (rated on 12) from the 15-items Short form of the McGill Pain questionnaire (SF-MPQ) .
Measured: through study completion, an average of 8 months
Pain interference scale
7 items rated from 0= does not interfere to 10= complete interference, total score 70 from the Brief Pain Inventory.
Measured: through study completion, an average of 8 months
Patients global impression of change
the 7 items Patients global impression of change (PGIC) (from very much worse to very much improved)
Measured: through study completion, an average of 8 months
The depression score
ranging from 0 to 13 with higher scores indicating more severe depression from the 13 items Beck Depression Inventory (BDI)
Measured: through study completion, an average of 8 months
release of neurotransmitters
Measured with magnetic resonance spectroscopy,MRS
Measured: through study completion, an average of 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2021
- Study start28 Feb 2022
- Primary completion31 Dec 2022
- Study completion30 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuropathic PainStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- Parallel groups
- Model description
- fifty NP patients were randomly assigned to 3 groups.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- min yan, prof, Study chair, The second affiliated hospital of Zhejiang University hangzhou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05168319
- Sponsor's protocol ID
- 2021-0751
- Status last verified
- Jan 2022
- First submitted
- 15 Dec 2021
- Last updated
- 31 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects and Mechanism of Prolonged Continuous Theta Burst Stimulation on Neuropathic Pain
- ClinicalTrials.gov ID
- NCT05168319
- Acronym / sponsor ID
- 2021-0751
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 28 Feb 2022 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 30 Jan 2023 (actual)
- First posted
- 23 Dec 2021 (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.
Neuropathic pain (NP) is one type of refractory chronic pain condition,medical treatments for NP is limited because of its poorly response. A noninvasive brain-stimulation method called transcranial magnetic stimulation (TMS) has garnered interest as an alternative treatment for intractable NP potentially through inducing therapeutic brain plasticity.Indeed, high-frequency (≥ 5 Hz) Repetitive TMS (rTMS) over the primary motor cortex (M1) is suggested to be able to reduce neuropathic pain in randomized controlled studies.Overall, the clinical application of rTMS in chronic pain is still limited by the response rate,the investigation of rTMS protocols is important for improving rTMS analgesia. Theta burst stimulation (TBS) mimics the bursts of neuronal firing which results in robust long-term potentiation. Continuous TBS (cTBS) is designed to decrease excitability, whereby prolonged cTBS (pcTBS, i.e. multiple cTBS being delivered continuously) has recently been demonstrated to increase excitability. More importantly, pcTBS was found to have comparable or even better analgesic effects than standard 10 Hz rTMS. These findings together call for more studies to validate the analgesic efficacy of pcTBS.
In this study, the investigators aim to assess and compare the efficacy of prolonged continuous theta burst stimulation (pcTBS) with 10HZ rTMS in NP patients.
Detailed description
The investigators designed a randomized, double-blind, sham-controlled study at 1 center. fifty NP patients were randomly assigned to 3 groups. A series of 5 daily pcTBS(1200 pulses/session) or 10-Hz rTMS (1500 pulses/session) of primary motor cortex (M1) or sham stimulation was applied to each patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- fifty NP patients were randomly assigned to 3 groups.
| Arm | Type | Receives |
|---|---|---|
| pcTBS | Experimental | Device: Repetitive transcranial magnetic stimulationpcTBS was administered to the left M1 at 80% resting motor threshold (RMT), consisting of a burst of 3 pulses given at 50 Hz repeated every 5 Hz. A total of 1,200 pulses were delivered with the TMS coil positioned in a posterior-anterior (PA) direction parallel to the midline. |
| 10HZ rTMS | Active comparator | Device: Repetitive transcranial magnetic stimulationThe rTMS protocol included 15 trains of 10-second stimulation given at 10 Hz to the left M1 at 80% resting motor threshold (RMT), with the inter-train interval being set to 50 seconds (1500 pulses) |
| Sham | Sham comparator | Device: Sham stimulationThe Sham stimulation was delivered using the same protocol, with the coil being orientated at 90° to the scalp so that the magnetic field would be delivered away from the scal |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- (1)woman or man over 18 and under 70 years old; （2）pain fulfilling the criteria for probable or definite peripheral neuropathic pain ; (3) pain for at least 3 months, continuous pain (at least four days per week), at least moderate intensity (≥ 4/10 assessed by VAS) ; (4) stable pharmacological treatment for pain at least 2 weeks before inclusion; (5) able to cooperate in completing questionnaire.
Key exclusion criteria (1 listed)
- (1) Any clinically significant or unstable ongoing medical or psychiatric disorder including major depression; (2) History of substance abuse (alcohol, drugs); (3) Past treatment with repetitive transcranial magnetic stimulation (rTMS); (4) Contraindications to rTMS (previous severe head trauma or neurosurgical intervention, past or current epilepsy, active brain tumor, intracranial hypertension, implanted ferromagnetic devices, e.g., cardiac pacemaker, neurostimulator, or cochlear implants); (5) other type of pain more severe than neuropathic pain; (6) Any difficulty to fill out questionnaires (due to language or cognitive problems); (7) impossibility to be followed during the time course of the study;
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 |
|---|---|---|
| Repetitive transcranial magnetic stimulationParticipants received 10HZ rTMS protocol consisted of 5 sessions over 5 consecutive workdays | Device | 10HZ rTMS |
| Repetitive transcranial magnetic stimulationParticipants received pcTBS protocol consisted of 5 sessions over 5 consecutive workdays | Device | pcTBS |
| Sham stimulationParticipants received Sham rTMS stimulations consisted of 5 sessions over 5 consecutive workdays | Device | Sham |
Primary outcome
The mean change from baseline in pain intensity measured with the visual-analogic scale (VAS)
Time frame: through study completion, an average of 8 months
The primary outcome measure was the mean change from baseline over the course of 5 (group by time interaction) in average pain intensity measured with the visual-analogic scale (VAS) ( 0= no pain and 10= maximal pain). Baseline average pain intensity was assessed at inclusion then on the day of randomization, just before the first rTMS session (day 1) and corresponded to the average of these two values.
7 secondary outcomes
Motor-evoked potential (MEP)
Time frame: through study completion, an average of 8 months
Cortical silent period (CSP)
Time frame: through study completion, an average of 8 months
The sensory dimension of pain and affective dimension of pain
Time frame: through study completion, an average of 8 months
Pain interference scale
Time frame: through study completion, an average of 8 months
Patients global impression of change
Time frame: through study completion, an average of 8 months
The depression score
Time frame: through study completion, an average of 8 months
release of neurotransmitters
Time frame: through study completion, an average of 8 months
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 31 Oct 2023.
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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.
min yan, prof study chair
The second affiliated hospital of Zhejiang University hangzhou
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive transcranial magnetic stimulation in people with Neuropathic Pain and Repetitive Transcranial Magnetic Stimulation, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
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 1 inclusion and 1 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 31 Oct 2023. 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 China. 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?
The mean change from baseline in pain intensity measured with the visual-analogic scale (VAS) (time frame: through study completion, an average of 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2023.