Ignite Creation Date:
2024-05-06 @ 7:12 PM
Last Modification Date:
2024-10-26 @ 3:02 PM
Study NCT ID:
NCT05937984
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-07-10
First Post:
2023-06-08
Brief Title:
Treatment for Painful Diabetic Neuropathy
Sponsor:
McMaster University
Organization:
McMaster University
Study Overview
Official Title:
Advanced Controlled Transcranial Magnetic Stimulation to Modulate Neuroplasticity and Alleviate Pain in Diabetic Neuropathy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Painful diabetic neuropathy pDN occurs in a subset of diabetic patients and is characterize by burning shooting and electric shock-like pain in the arms and legs This represents a major health crisis given the increasing prevalence of pDN and the significant impact it has on quality of life However there is limited evidence of effective therapies for pDN pain relief Repetitive transcranial magnetic stimulation rTMS is a non-invasive form of brain stimulation that may be a promising therapy for pDN Previous research has shown that rTMS reduces neuropathic pain in pDN 1 2 3 While this is promising it is important to note that rTMS is effective for 50 of patients with neuropathic pain 4 5 Recent advancements in rTMS technology have created the opportunity for remarkable strides in the effectiveness of this potential therapy This new development called controlled pulse parameter TMS cTMS increases the magnitude and longevity of TMS-induced effects Although not tested in chronic pain cTMS possess the power to make transformative changes in pDN potentially yielding greater and widespread improvements in pain The overarching goal of the proposed research is to assess the effects of a 5-day cTMS stimulation protocol on measures of pain and neurological function in individuals with pDN
1 Kwak S Choi SG Chang GS Yang MC 2022 Short-term Effect of Repetitive Transcranial Magnetic Stimulation on Diabetic Peripheral Neuropathic Pain Pain Physician 252 E203-E209
2 Abdelkader AA Gohary AME Mourad HS Salmawy DAE 2019 Repetitive tms in treatment of resistant diabetic neuropathic pain Egyptian Journal of Neurology Psychiatry and Neurosurgery 551
3 Onesti E et al 2013 H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy European Journal of Pain United Kingdom 179
4 Attal N et al 2021 Repetitive transcranial magnetic stimulation for neuropathic pain a randomized multicentre sham-controlled trial Brain 14411
65 Dongyang L et al 2021 Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain - A pilot double-blind randomized cross-over study Neurophysiologie Clinique 514
1 Kwak S Choi SG Chang GS Yang MC 2022 Short-term Effect of Repetitive Transcranial Magnetic Stimulation on Diabetic Peripheral Neuropathic Pain Pain Physician 252 E203-E209
2 Abdelkader AA Gohary AME Mourad HS Salmawy DAE 2019 Repetitive tms in treatment of resistant diabetic neuropathic pain Egyptian Journal of Neurology Psychiatry and Neurosurgery 551
3 Onesti E et al 2013 H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy European Journal of Pain United Kingdom 179
4 Attal N et al 2021 Repetitive transcranial magnetic stimulation for neuropathic pain a randomized multicentre sham-controlled trial Brain 14411
65 Dongyang L et al 2021 Posterior-superior insular deep transcranial magnetic stimulation alleviates peripheral neuropathic pain - A pilot double-blind randomized cross-over study Neurophysiologie Clinique 514
Detailed Description:
Background Diabetic neuropathy is one of the most common complications of diabetes occurring in 50 of patients 1 2 Of these individuals 20 will develop painful diabetic neuropathy pDN 3 as a consequence of abnormal changes in the peripheral somatosensory system 4 pDN is characterized by sensory changes including hyperalgesia allodynia paresthesia and burning shooting and electric shock-like pain affecting lower and upper extremities 4-6 pDN is a result of high glucose concentrations that damages peripheral nerves 7 resulting in hyperexcitability of nociceptive neurons in the dorsal horn and central sensitization 8 pDN is also marked by alterations in the central nervous system 6 including the descending modulatory system 9 and maladaptive changes to somatosensory and motor areas 10 pDN is associated with decreased quality of life anxiety and depression 5 The treatment of pDN currently involves opioid agonist antidepressants and anticonvulsants however these drugs are associated with undesired side effects 11 and only achieve a 50 reduction in pain with delayed onset 12 Importantly the prevalence of pDN is increasing 13 and given the limited effectiveness of pharmacological interventions pDN represents a major healthcare crisis
Repetitive transcranial magnetic stimulation rTMS may be a beneficial therapy for patients with pDN Sham controlled studies 14-19 and meta-analyses 20-23 have demonstrated that high frequency rTMS stimulation applied to the primary motor cortex reduces symptoms of neuropathic pain in heterogenous groups of patients 24 Our lab recently demonstrated that rTMS is effective at alleviating electric attacks in an individual with NP following SCI 25 rTMS is also effective in pDN Yang 26 found analgesic relief one day following stimulation to the hand representation of the primary motor cortex that persisted for 1 week rTMS was also associated with significant improvements in physical and mental health measured using the SF-36 physical component score and mental component score respectively 26 Abdelkader 27 indicated pain relief at 3 weeks post rTMS in patients with insulin-dependent and non-insulin-dependent pDN as well as improvements in lower limb nerve conduction latency and velocity Comparatively Onesti 8 targeted the leg representation in the primary motor cortex rTMS reduced pain compared to sham immediately post stimulation but did not persist at three weeks 8 rTMS also produced a depression of spinal nociceptive neurons as indicated through a decrease in the area of nociceptive flexion RIII reflex 8 This finding suggests that rTMS increases the firing rates of cells in motor cortex and increases corticospinal excitability and neuroplasticity These changes are thought to modulate descending inhibitory pain pathways through spinal interneural networks producing hypoexcitability of spinal nociceptive neurons 8 Although the few studies in pDN demonstrate promise it is important to note that rTMS is effective for 50 of patients with neuropathic pain 24 28 leaving much room for further improvement
Recent advancements in rTMS technology have created the opportunity for remarkable strides in neuroplasticity This new development called controlled pulse parameter TMS cTMS increases the magnitude and longevity of rTMS induced plasticity in humans 29 30 Fundamental to previous ie traditional rTMS is the biphasic pulse shape that are used during stimulation In cTMS pulses are monophasic and modifiable and can be delivered at high rates used in rTMS 31 32 Although not tested in chronic pain cTMS possess the power to make transformative changes in pDN potentially yielding greater and widespread improvements in pain The overarching goal of the proposed research is to assess the effects of a 10-day cTMS stimulation protocol on measures of pain neuroplasticity and somatosensory function in individuals with pDN
How is cTMS thought to induce neuroplasticity and reduce pain The primary motor cortex M1 is directly implicated in modulating pain signals 33 through descending inhibitory control to thalamus 34 35 and its connections with pain processing areas 36 including somatosensory 37 anterior cingulate cortex and prefrontal cortices 38 39 The analgesic effect of rTMS is suggested to occur by re-establishing both intracortical inhibition 40 GABAergic inhibition 41 43 and descending inhibitory control 34 35 cTMS may more readily activate and cause change in the circuits projecting to these areas Specifically monophasic pulses delivered with repetitive cTMS produce larger and more long-lasting changes in cortical excitability 29 and greater depths of inhibition compared to traditional biphasic rTMS 30 Monophasic pulses also produce more reliable cortical responses in cortical excitability intracortical and GABAergic inhibition 44 These findings have been suggested to occur as a result of the uniform pattern of cortical activation from monophasic pulses Monophasic pulses produce greater global mean field power GMFP measured through electroencephalography EEG compared to biphasic 31 Specifically biphasic pulses may activate populations of both excitatory and inhibitory neurons which may dampen the overall effects of the stimulation protocol 29 Taken together cTMS may facilitate a greater propensity for change in these circuits and ultimately pain relief when applied to individuals with NP The specific aims of this study in pDN are to
1 Investigate the effects of a 10-day cTMS intervention on pain symptoms The investigators hypothesize that cTMS will produce analgesic relief that will be associated with changes in neuroplasticity and somatosensory function compared to sham Importantly the effect of real and sham cTMS will be explored within individuals
2 To explore the feasibility of the 10-day cTMS intervention This will inform the utility of cTMS interventions in future treatments studies In addition the patient perceived change from the intervention will be assessed to improve the patient experience for future studies
3 To assess the effects of the 10-day cTMS intervention on neurophysiology and somatosensory function It is hypothesized that cTMS will produce neuromodulatory effects associated with increased cortical excitability GABAergic inhibition neuroplasticity and improve somatosensory function compared to sham
Repetitive transcranial magnetic stimulation rTMS may be a beneficial therapy for patients with pDN Sham controlled studies 14-19 and meta-analyses 20-23 have demonstrated that high frequency rTMS stimulation applied to the primary motor cortex reduces symptoms of neuropathic pain in heterogenous groups of patients 24 Our lab recently demonstrated that rTMS is effective at alleviating electric attacks in an individual with NP following SCI 25 rTMS is also effective in pDN Yang 26 found analgesic relief one day following stimulation to the hand representation of the primary motor cortex that persisted for 1 week rTMS was also associated with significant improvements in physical and mental health measured using the SF-36 physical component score and mental component score respectively 26 Abdelkader 27 indicated pain relief at 3 weeks post rTMS in patients with insulin-dependent and non-insulin-dependent pDN as well as improvements in lower limb nerve conduction latency and velocity Comparatively Onesti 8 targeted the leg representation in the primary motor cortex rTMS reduced pain compared to sham immediately post stimulation but did not persist at three weeks 8 rTMS also produced a depression of spinal nociceptive neurons as indicated through a decrease in the area of nociceptive flexion RIII reflex 8 This finding suggests that rTMS increases the firing rates of cells in motor cortex and increases corticospinal excitability and neuroplasticity These changes are thought to modulate descending inhibitory pain pathways through spinal interneural networks producing hypoexcitability of spinal nociceptive neurons 8 Although the few studies in pDN demonstrate promise it is important to note that rTMS is effective for 50 of patients with neuropathic pain 24 28 leaving much room for further improvement
Recent advancements in rTMS technology have created the opportunity for remarkable strides in neuroplasticity This new development called controlled pulse parameter TMS cTMS increases the magnitude and longevity of rTMS induced plasticity in humans 29 30 Fundamental to previous ie traditional rTMS is the biphasic pulse shape that are used during stimulation In cTMS pulses are monophasic and modifiable and can be delivered at high rates used in rTMS 31 32 Although not tested in chronic pain cTMS possess the power to make transformative changes in pDN potentially yielding greater and widespread improvements in pain The overarching goal of the proposed research is to assess the effects of a 10-day cTMS stimulation protocol on measures of pain neuroplasticity and somatosensory function in individuals with pDN
How is cTMS thought to induce neuroplasticity and reduce pain The primary motor cortex M1 is directly implicated in modulating pain signals 33 through descending inhibitory control to thalamus 34 35 and its connections with pain processing areas 36 including somatosensory 37 anterior cingulate cortex and prefrontal cortices 38 39 The analgesic effect of rTMS is suggested to occur by re-establishing both intracortical inhibition 40 GABAergic inhibition 41 43 and descending inhibitory control 34 35 cTMS may more readily activate and cause change in the circuits projecting to these areas Specifically monophasic pulses delivered with repetitive cTMS produce larger and more long-lasting changes in cortical excitability 29 and greater depths of inhibition compared to traditional biphasic rTMS 30 Monophasic pulses also produce more reliable cortical responses in cortical excitability intracortical and GABAergic inhibition 44 These findings have been suggested to occur as a result of the uniform pattern of cortical activation from monophasic pulses Monophasic pulses produce greater global mean field power GMFP measured through electroencephalography EEG compared to biphasic 31 Specifically biphasic pulses may activate populations of both excitatory and inhibitory neurons which may dampen the overall effects of the stimulation protocol 29 Taken together cTMS may facilitate a greater propensity for change in these circuits and ultimately pain relief when applied to individuals with NP The specific aims of this study in pDN are to
1 Investigate the effects of a 10-day cTMS intervention on pain symptoms The investigators hypothesize that cTMS will produce analgesic relief that will be associated with changes in neuroplasticity and somatosensory function compared to sham Importantly the effect of real and sham cTMS will be explored within individuals
2 To explore the feasibility of the 10-day cTMS intervention This will inform the utility of cTMS interventions in future treatments studies In addition the patient perceived change from the intervention will be assessed to improve the patient experience for future studies
3 To assess the effects of the 10-day cTMS intervention on neurophysiology and somatosensory function It is hypothesized that cTMS will produce neuromodulatory effects associated with increased cortical excitability GABAergic inhibition neuroplasticity and improve somatosensory function compared to sham
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None