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Mechanism of Analgesic Effect on Prolonged Continuous Theta Burst Stimulation

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ClinicalTrials.gov Identifier: NCT05360030
Recruitment Status : Not yet recruiting
First Posted : May 4, 2022
Last Update Posted : May 4, 2022
Sponsor:
Information provided by (Responsible Party):
Second Affiliated Hospital, School of Medicine, Zhejiang University

Tracking Information
First Submitted Date  ICMJE April 19, 2022
First Posted Date  ICMJE May 4, 2022
Last Update Posted Date May 4, 2022
Estimated Study Start Date  ICMJE May 1, 2022
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2022)
  • pain intensity at baseline [ Time Frame: Baseline ]
    pain intensity on a 10-cm visual analogue scale (VAS) extending from 0 (no pain) to 100 (maximal pain possible) at baseline.
  • pain intensity at the posttreatment of pcTBS [ Time Frame: through study completion, an average of 8 months ]
    pain intensity on a 10-cm visual analogue scale (VAS) extending from 0 (no pain) to 100 (maximal pain possible) at the posttreatment of pcTBS.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2022)
  • Motor-evoked potential (MEP) [ Time Frame: through study completion, an average of 8 months ]
    Corticospinal excitability will be 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).
  • Cortical silent period (CSP) [ Time Frame: through study completion, an average of 8 months ]
    Corticospinal excitability will be 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).
  • Maximum plasma concentration of opioid peptide at baseline [ Time Frame: baseline ]
    plasma opioid peptide concentrations will be measured using ELISA at baseline.
  • Maximum plasma concentration of opioid peptide at the posttreatment of pcTBS [ Time Frame: through study completion, an average of 8 months ]
    plasma opioid peptide concentrations will be measured using ELISA at the last posttreatment of pcTBS.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanism of Analgesic Effect on Prolonged Continuous Theta Burst Stimulation
Official Title  ICMJE Mechanism of Analgesic Effect on Prolonged Continuous Theta Burst Stimulation
Brief Summary It has been shown that prolonged continuous theta burst stimulation (pcTBS) , a relatively new repetitive transcranial magnetic simulation (rTMS) protocol, of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) decreases pain in healthy volunteers, in various experimental models. In addition, rTMS of M1 has also been shown to have analgesic effects in various chronic pain conditions, including neuropathic pain.The mechanisms underlying rTMS-induced analgesia remain unclear. Functional neuroimaging studies have shown that rTMS of M1 and DLPFC induces changes in the activity of cortical and subcortical structures involved in pain processing and modulation. Endogenous opioids and e N-methyl-D-aspartate (NMDA) receptor are known to play a major role in these processes. The investigator hypothesized that the endogenous opioids systems (EOS) and NMDA receptor might be involved in the analgesic action of pcTBS. In the first part,the investigator compares the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after naloxone or placebo treatment, the intensity of pain induced by capsaicin were used to evaluate the analgesic effects of pcTBS. If naloxone does not reverse the analgesic effect of pcTBS,The volunteers will be invited to participant the second part of the study, which the investigator compares the analgesic effects of motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) stimulation before and after Ketamine treatment.
Detailed Description This study comprised 3 parallel arms corresponding to 3 types of stimulation: active stimulation of M1, active stimulation of DLPFC-pcTBS, and sham stimulation (of M1 or DLPFC). Volunteers were randomly assigned to the 3 arms. In the first part, these volunteers participated in 2 experimental sessions 1 weeks apart, in which we compared the effects of naloxone and placebo (saline), administered according to a randomized, double-blind crossover design, on pcTBS-induced analgesia. Each experimental session started with the determination of baseline pain intensity and cortical excitability as well as plasma opioid peptide concentrations. Ten minutes before pcTBS (of M1, DLPFC, or sham), the volunteer received an intravenous bolus followed by a continuous infusion of either placebo (ie, saline) or naloxone, which was continued throughout the rTMS session (2 minutes). The participant was then allowed to rest for 60 minutes. Posttreatment pain intensity, cortical excitability and plasma opioid peptide concentrations will be determined by the same procedure used at baseline.In the second part, ketamine will be delivered the same as the first part.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Chronic Pain
  • rTMS
Intervention  ICMJE
  • Drug: Naloxone
    The volunteer received an intravenous bolus followed by a continuous infusion of naloxone, which was continued throughout the pcTBS session
  • Drug: Saline
    The volunteer received an intravenous bolus followed by a continuous infusion of placebo (saline), which was continued throughout the pcTBS session
  • Drug: Ketamine Hydrochloride
    The volunteer received an intravenous bolus followed by a continuous infusion of ketamine, which was continued throughout the pcTBS session
  • Device: pcTBS of M1
    Prolonged continuous theta-burst stimulation (pcTBS) was administered to the left M1 at 80% 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
  • Device: pcTBS of DLPFC
    Prolonged continuous theta-burst stimulation (pcTBS) was administered to the left DLPFC at 80% 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
  • Device: SHAM stimulation
    The Sham stimulation was delivered using the same pcTBS protocol, with the coil being flipped 90◦to the scalp so that the magnetic field would be delivered away from the scalp
Study Arms  ICMJE
  • Experimental: active stimulation of M1
    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.
    Interventions:
    • Drug: Naloxone
    • Drug: Saline
    • Drug: Ketamine Hydrochloride
    • Device: pcTBS of M1
  • Experimental: active stimulation of DLPFC
    pcTBS was administered to the left DLPFC 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.
    Interventions:
    • Drug: Naloxone
    • Drug: Saline
    • Drug: Ketamine Hydrochloride
    • Device: pcTBS of DLPFC
  • Sham Comparator: SHAM stimulation
    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
    Interventions:
    • Drug: Naloxone
    • Drug: Saline
    • Drug: Ketamine Hydrochloride
    • Device: SHAM stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2022)
45
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date May 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

1)woman or man over 18 and under 85 years old; 2)Clinical diagnosis of physical and mental health people; 3) able to cooperate in completing questionnaire.

Exclusion Criteria:

1)Clinical diagnosis of 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) Any difficulty to fill out questionnaires (due to language or cognitive problems);

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: ying liu, doctor 15595512306 350373328@qq.com
Contact: min yan, prof. zryanmin@zju.edu.cn
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05360030
Other Study ID Numbers  ICMJE RI2022089
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Second Affiliated Hospital, School of Medicine, Zhejiang University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Second Affiliated Hospital, School of Medicine, Zhejiang University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: min yan, prof The second affiliated hospital of Zhejiang University hangzhou
PRS Account Second Affiliated Hospital, School of Medicine, Zhejiang University
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP