Diabetic NeuropathiesNCT04306289
tDCS and Pain Associated With Diabetic Neuropathy
A study testing transcranial direct current stimulation in people with Diabetic Neuropathies and Chronic Pain, run by University of Rome Tor Vergata at 1 site in Italy.
Trial summary
The purpose of this study is to investigate the effects of anodal transcranial direct current stimulation (tDCS) on pain intensity associated with diabetic neuropathy. The investigators will conduct real tDCS or sham, over the left dorsolateral prefrontal cortex (DLPFC) during 6 separated days. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetic Neuropathies, Chronic Pain
- What is being tested?
- transcranial direct current stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2020to 1 Sep 2022
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient diagnosed with painful diabetic peripheral neuropathy (PDPN) components with DN4 score ≥ 4/10, and chronic pain with an intensity of at least VAS> 4/10.
- Onset of neuropathic PDPN pain for at least 6 months.
- Pain intensity as measured by VAS> 4/10 in the week preceding inclusion in the study.
- drug-resistant patients who have no pain reduction of 50% or an improvement of at least 2 points in the Patient Global Impression of Change, having used all the classes of drugs indicated as a first, second or third line.
- Absence of glycemic de-compensation with HbA1c values <9% in the previous 6 months.
- Stability of glycemic control with changes in HbA1c in the last 6 months of less than 2%.
Who cannot join
- Neurological comorbidities.
- Presence of contraindications to the use of electrotherapy (pacemaker, epilepsy, etc ...).
- Pregnancy.
- Previous neurosurgical interventions.
- psychiatric conditions.
- Cognitive impairments ( Mini-Mental Status exam (MMSE) <24).
- Presence of red flags for pain: tumors, spine fractures, non-neuropathic pain difficult to distinguish from that of the PDPN, neuropathic pain from a cause other than the PDPN.
- Severe comorbidities such as advanced renal failure, heart failure, respiratory failure.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Prof. Silvia Natoli
Rome, Lazio, 00133
Silvia Natoli, MD, PhD, +393451690925, silvia.natoli@uniroma2.it
Mohammad Alwardat, PT, PhD, +393296423074, wardatm1@gmail.com
About this study
Official title: Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Associated With Diabetic Neuropathy
The purpose of this study is to investigate the effects of anodal transcranial direct current stimulation (tDCS) on pain intensity associated with diabetic neuropathy. The investigators will conduct real tDCS or sham, over the left dorsolateral prefrontal cortex (DLPFC) during 6 separated days. They will evaluate pain intensity, sleep quality, quality of life and anxiety and depression symptoms via clinical validated scales.
The research question is whether tDCS can lessen neuropathic pain and improve sleep, psychological status and quality of life in patients with diabetic neuropathy.
It is hypothesized, that less neuropathic pain and improved sleep, psychological status and quality of life after the tDCS sessions.
Read the detailed description
Background: Worldwide, the prevalence of diabetes mellitus (DM) and its chronic complications are reaching epidemic proportions. By 2045 DM expected to affect 629 million persons. Diabetic neuropathy is one of the most common complications of DM and is actually the set of heterogeneous clinical forms. Among diabetic neuropathies, generalized, focal or multifocal forms are distinguished. The most typical and most common form (up to 80% of cases is sensory-motor polyneuropathy. It has recently been redefined as a length-dependent symmetric sensory-motor polyneuropathy attributable to metabolic and microvascular alterations following exposure to chronic hyperglycemia and cardiovascular risk cofactors. Painful diabetic peripheral neuropathy (PDPN) may be considered a variant; about 15-25% of patients have painful diabetic polyneuropathy.
According to the definition of neuropathic pain of the International Association for the Study of Pain (IASP), PDPN is considered as asymmetric sensory-motor polyneuropathy chronic in which neuropathic pain has been present, for at least 3 months, as direct consequence abnormalities of the peripheral somatic-sensitive system following diabetic pathology. Sensory symptoms are more evident than motor symptoms; which is appear in the most distal portions of the limbs and progress proximally according to a "glove" or "sock" distribution associated with paresthesias and dysesthesias. The clinical symptoms are related to the type of nerve fiber involved and typically there are "positive" (tingling, burning, pain, allodynia) or "negative" sensory symptoms (loss of sensitivity, numbness). The involvement of small sensitive fibers causes a reduction in thermal sensitivity and pain and this, in turn, contributes to the deficits in tactile and proprioceptive sensitivity to increase the risk of a foot injury.
The PDPN is associated with negative repercussions on the quality of life (QoL), activities of daily livings, sleep disorders, and is the major determinant of depressive symptoms in patients with PDNP. In fact, depression and sleep disturbances play a negative prognostic role in the general and diabetic population, and sleep disturbances are associated with glycated hemoglobin levels higher than 0.35% in type 2 diabetes. The presence of PDPN determines an increase in the use of medical care and social costs, both directly related to treatments, and indirect secondary to the reduction of working capacity. The presence of chronic pain of any nature increases the risk of difficulties in the self-management of diabetes, in relation to taking therapy, physical activity, adherence to the diet, foot care and even glycemic self-monitoring.
Transcranial Direct Current Stimulation (tDCS) has shown promising results for the treatment of chronic pain in several types of diseases, being a good and non-invasive alternative to treat pain in PDPN patients. Also, based on studies that showed changes in the brain activity of chronic pain patients and on the difficulties faced to treat PDPN, there is a need to conduct clinical trials using new techniques, such as neuromodulation, to help these patients to control their pain. Therefore, tDCS emerges as a new tool to be coupled with other effective treatments already used for these patients.
The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region as well as a key area of numerous brain networks involved in the processing of cognition effect. Numerous studies have shown that some chronic pain syndromes are associated with a reduction in the volume of the gray matter of DLPFC. Some studies show that pain relief manages to reverse these structural changes PDPN. Moreover, previous studies reported that DLPFC stimulation induces a significant analgesic and antidepressant effect.
Hypothesis: The investigators believe that neuromodulation by tDCS over the left DLPFC would decrease the pain intensity and improve the general quality of life in patients with PDPN.
Objectives: general PURPOSE Investigate if anodal tDCS over left DLPFC has analgesic effects in patients with PDPN.
Specifics purposes 1- Evaluate the tDCS effects over pain intensity; 2- Evaluate if tDCS has any effect on sleep quality, depression, anxiety, and quality of life.
Randomization: The subjects will be allocated consecutively to randomization as an intervention order using the tool from the randomization.com website (Dallal GE, http://www.randomization.com). The investigators will use the second generation suggested for crossover studies.
Data Collection Procedure: All subjects will be treated using two different interventions (groups respecting the washout period of six weeks to avoid residual effects. The intervention order will be determined by randomization per group of interventions. Subjects will be contacted by phone and asked if they want to participate in the study. Those who wish to participate and qualify according to the selection criteria after completing the pre-screening questionnaire will be scheduled after reading and signing the consent form (2 copies). During the second visit, all clinical and neurological assessments will be performed before and after tDCS stimulation phase. Each patient will be clinically and neurologically assessed before and after the stimulation, allowing data to be collected 4 times (T0, T1, T2, and T3).
tDCS protocol: Group Real tDCS: The participant will receive anodal tDCS over the left DLPFC and the reference electrode will place over the right forearm. The stimulation intensity will be 2mA DC delivered for 20 min (30 s step-up ramp, 30 s step-down ramp), repeated six times, during two weeks (Mon, Wed, Frid).
Group sham tDCS: Identical to the real tDCS, except the participants will only receive the initial 30 seconds of ramp-up, after which the current will be set to 0 for the remainder of the 20 minutes.
- Conditions
- Diabetic Neuropathies, Chronic Pain
- Being tested
- transcranial direct current stimulation
- Keywords
- chronic pain, transcranial direct current stimulation, Diabetic Neuropathy, Quality of life
- Medical subject headings
- Diabetic Neuropathies, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial direct current stimulationDevice
Transcranial direct current stimulation (tDCS) is a noninvasive technique of neuronal modulation that has been used in different neurological conditions, neuropathic pain.
| Study group | Role | What they receive |
|---|---|---|
| Real tDCS | Active comparator | The participant will receive anodal tDCS for 20 min at an intensity of 2 mA while seated comfortably and quietly in a room. The intensity will start at 0 mA and will be incrementally increased to 2mA over the initial 30 seconds. At the 19:30 minute time point, the current will gradually be reduced from 2 mA to 0 mA. Receives: Device: transcranial direct current stimulation |
| Sham tDCS | Sham comparator | Identical to the real tDCS, except the participants will only receive the initial 30 seconds of ramp-up, after which the current will be set to 0 for the remainder of the 20 minutes. Receives: Device: transcranial direct current stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Pain severity
Changes in Pain severity will be measured by Brief Pain Inventory (BPI) to determine the effect of anodal Transcranial direct current stimulation (tDCS) in reducing pain of subjects with pain associated with diabetic neuropathy.
Measured: Measured at baseline and immediately after the intervention
Secondary outcomes (7)
Changes in Depression severity
Changes in depression severity will be measured by Hamilton Depression scale (HAM-D) to determine the effect of anodal Transcranial direct current stimulation (tDCS) in reducing depression severity of subjects with pain associated with diabetic neuropathy.
Measured: Measured at baseline and immediately after the intervention
Changes in Anxiety severity
Changes in Anxiety severity will be measured by Hamilton Anxiety scale (HAM-A) to determine the effect of anodal Transcranial direct current stimulation (tDCS) in reducing anxiety severity of subjects with pain associated with diabetic neuropathy.
Measured: Measured at baseline and immediately after the intervention
Changes in sleep quality
Changes in Sleep quality will be measured by Pittsburgh sleep quality index (PSQI) to determine the effect of anodal Transcranial direct current stimulation (tDCS) in improving sleep quality of subjects with pain associated with diabetic neuropathy.
Measured: Measured at baseline and immediately after the intervention
Changes in Quality of Life
Changes in quality of life will be measured by SF-36 to determine the effect of anodal Transcranial direct current stimulation (tDCS) in improving quality of life of subjects with pain associated with diabetic neuropathy.
Measured: Measured at baseline and immediately after the intervention
Changes in Pain related to disability
The investigators will use the Pain Disability Index (PDI) to assess changes in pain related to disability.
Measured: Measured at baseline and immediately after the intervention
Changes in Pain Catastrophizing
The investigators will use the Pain Catastrophizing Scale (PCS) to assess changes in pain Catastrophizing.
Measured: Measured at baseline and immediately after the intervention
Changes in Neuropathic Pain Symptom
Changes in neuropathic pain symptoms will be measured by Neuropathic Pain Symptom Inventory (NPSI) to determine the effect of anodal Transcranial direct current stimulation (tDCS) in improving and/or reducing neuropathic pain symptom of subjects with pain associated with diabetic neuropathy.
Measured: Measured at baseline and immediately 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 posted12 Mar 2020
- Study start1 Jun 2020
- Primary completion6 Jun 2022 (estimated)
- Study completion1 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Diabetic NeuropathiesStudies of the same condition, open and under way.
- 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
- Model description
- Crossover Assignment
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rome Tor Vergata
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammad Alwardat, University of Rome Tor Vergata
- Investigators
- Slivia Natoli, MD, PhD, Study director, Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04306289
- Sponsor's protocol ID
- University of Rome Tor Vergata
- Status last verified
- Aug 2021
- First submitted
- 3 Mar 2020
- Last updated
- 10 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O'Brien PC, Melton LJ 3rd, Service FJ. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr;43(4):817-24. doi: 10.1212/wnl.43.4.817.
PubMed 8469345Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-154. doi: 10.2337/dc16-2042. No abstract available.
PubMed 27999003Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH; EURODIAB Prospective Complications Study Group. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005 Jan 27;352(4):341-50. doi: 10.1056/NEJMoa032782.
PubMed 15673800Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303.
PubMed 20876709Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med. 2004 Sep;21(9):976-82. doi: 10.1111/j.1464-5491.2004.01271.x.
PubMed 15317601Abbott CA, Malik RA, van Ross ER, Kulkarni J, Boulton AJ. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care. 2011 Oct;34(10):2220-4. doi: 10.2337/dc11-1108. Epub 2011 Aug 18.
PubMed 21852677Alleman CJ, Westerhout KY, Hensen M, Chambers C, Stoker M, Long S, van Nooten FE. Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature. Diabetes Res Clin Pract. 2015 Aug;109(2):215-25. doi: 10.1016/j.diabres.2015.04.031. Epub 2015 May 6.
PubMed 26008721Binns-Hall O, Selvarajah D, Sanger D, Walker J, Scott A, Tesfaye S. One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot. Diabet Med. 2018 Jul;35(7):887-894. doi: 10.1111/dme.13630. Epub 2018 May 10.
PubMed 29608799Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008 Apr 29;70(18):1630-5. doi: 10.1212/01.wnl.0000282763.29778.59. Epub 2007 Nov 14.
PubMed 18003941D'Amato C, Morganti R, Greco C, Di Gennaro F, Cacciotti L, Longo S, Mataluni G, Lauro D, Marfia GA, Spallone V. Diabetic peripheral neuropathic pain is a stronger predictor of depression than other diabetic complications and comorbidities. Diab Vasc Dis Res. 2016 Nov;13(6):418-428. doi: 10.1177/1479164116653240. Epub 2016 Jun 22.
PubMed 27334483Ziegler D, Rathmann W, Dickhaus T, Meisinger C, Mielck A; KORA Study Group. Neuropathic pain in diabetes, prediabetes and normal glucose tolerance: the MONICA/KORA Augsburg Surveys S2 and S3. Pain Med. 2009 Mar;10(2):393-400. doi: 10.1111/j.1526-4637.2008.00555.x. Epub 2009 Jan 16.
PubMed 19207236Van Acker K, Bouhassira D, De Bacquer D, Weiss S, Matthys K, Raemen H, Mathieu C, Colin IM. Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics. Diabetes Metab. 2009 Jun;35(3):206-13. doi: 10.1016/j.diabet.2008.11.004. Epub 2009 Mar 17.
PubMed 19297223Wu YJ, Lin CC, Yeh CM, Chien ME, Tsao MC, Tseng P, Huang CW, Hsu KS. Repeated transcranial direct current stimulation improves cognitive dysfunction and synaptic plasticity deficit in the prefrontal cortex of streptozotocin-induced diabetic rats. Brain Stimul. 2017 Nov-Dec;10(6):1079-1087. doi: 10.1016/j.brs.2017.08.007. Epub 2017 Aug 24.
PubMed 28870510Kim YJ, Ku J, Kim HJ, Im DJ, Lee HS, Han KA, Kang YJ. Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy. Ann Rehabil Med. 2013 Dec;37(6):766-76. doi: 10.5535/arm.2013.37.6.766. Epub 2013 Dec 23.
PubMed 24466511Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29.
PubMed 27866120
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Associated With Diabetic Neuropathy
- ClinicalTrials.gov ID
- NCT04306289
- Acronym / sponsor ID
- University of Rome Tor Vergata
- Conditions
- Diabetic Neuropathies, Chronic Pain
- Keywords
- chronic pain, transcranial direct current stimulation, Diabetic Neuropathy, Quality of life
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Rome Tor VergataUniversity, hospital or other
- Study start
- 1 Jun 2020 (actual)
- Primary completion
- 6 Jun 2022 (estimated)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 12 Mar 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.
The purpose of this study is to investigate the effects of anodal transcranial direct current stimulation (tDCS) on pain intensity associated with diabetic neuropathy. The investigators will conduct real tDCS or sham, over the left dorsolateral prefrontal cortex (DLPFC) during 6 separated days. They will evaluate pain intensity, sleep quality, quality of life and anxiety and depression symptoms via clinical validated scales.
The research question is whether tDCS can lessen neuropathic pain and improve sleep, psychological status and quality of life in patients with diabetic neuropathy.
It is hypothesized, that less neuropathic pain and improved sleep, psychological status and quality of life after the tDCS sessions.
Detailed description
Background: Worldwide, the prevalence of diabetes mellitus (DM) and its chronic complications are reaching epidemic proportions. By 2045 DM expected to affect 629 million persons. Diabetic neuropathy is one of the most common complications of DM and is actually the set of heterogeneous clinical forms. Among diabetic neuropathies, generalized, focal or multifocal forms are distinguished. The most typical and most common form (up to 80% of cases is sensory-motor polyneuropathy. It has recently been redefined as a length-dependent symmetric sensory-motor polyneuropathy attributable to metabolic and microvascular alterations following exposure to chronic hyperglycemia and cardiovascular risk cofactors. Painful diabetic peripheral neuropathy (PDPN) may be considered a variant; about 15-25% of patients have painful diabetic polyneuropathy.
According to the definition of neuropathic pain of the International Association for the Study of Pain (IASP), PDPN is considered as asymmetric sensory-motor polyneuropathy chronic in which neuropathic pain has been present, for at least 3 months, as direct consequence abnormalities of the peripheral somatic-sensitive system following diabetic pathology. Sensory symptoms are more evident than motor symptoms; which is appear in the most distal portions of the limbs and progress proximally according to a "glove" or "sock" distribution associated with paresthesias and dysesthesias. The clinical symptoms are related to the type of nerve fiber involved and typically there are "positive" (tingling, burning, pain, allodynia) or "negative" sensory symptoms (loss of sensitivity, numbness). The involvement of small sensitive fibers causes a reduction in thermal sensitivity and pain and this, in turn, contributes to the deficits in tactile and proprioceptive sensitivity to increase the risk of a foot injury.
The PDPN is associated with negative repercussions on the quality of life (QoL), activities of daily livings, sleep disorders, and is the major determinant of depressive symptoms in patients with PDNP. In fact, depression and sleep disturbances play a negative prognostic role in the general and diabetic population, and sleep disturbances are associated with glycated hemoglobin levels higher than 0.35% in type 2 diabetes. The presence of PDPN determines an increase in the use of medical care and social costs, both directly related to treatments, and indirect secondary to the reduction of working capacity. The presence of chronic pain of any nature increases the risk of difficulties in the self-management of diabetes, in relation to taking therapy, physical activity, adherence to the diet, foot care and even glycemic self-monitoring.
Transcranial Direct Current Stimulation (tDCS) has shown promising results for the treatment of chronic pain in several types of diseases, being a good and non-invasive alternative to treat pain in PDPN patients. Also, based on studies that showed changes in the brain activity of chronic pain patients and on the difficulties faced to treat PDPN, there is a need to conduct clinical trials using new techniques, such as neuromodulation, to help these patients to control their pain. Therefore, tDCS emerges as a new tool to be coupled with other effective treatments already used for these patients.
The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region as well as a key area of numerous brain networks involved in the processing of cognition effect. Numerous studies have shown that some chronic pain syndromes are associated with a reduction in the volume of the gray matter of DLPFC. Some studies show that pain relief manages to reverse these structural changes PDPN. Moreover, previous studies reported that DLPFC stimulation induces a significant analgesic and antidepressant effect.
Hypothesis: The investigators believe that neuromodulation by tDCS over the left DLPFC would decrease the pain intensity and improve the general quality of life in patients with PDPN.
Objectives: general PURPOSE Investigate if anodal tDCS over left DLPFC has analgesic effects in patients with PDPN.
Specifics purposes 1- Evaluate the tDCS effects over pain intensity; 2- Evaluate if tDCS has any effect on sleep quality, depression, anxiety, and quality of life.
Randomization: The subjects will be allocated consecutively to randomization as an intervention order using the tool from the randomization.com website (Dallal GE, http://www.randomization.com). The investigators will use the second generation suggested for crossover studies.
Data Collection Procedure: All subjects will be treated using two different interventions (groups respecting the washout period of six weeks to avoid residual effects. The intervention order will be determined by randomization per group of interventions. Subjects will be contacted by phone and asked if they want to participate in the study. Those who wish to participate and qualify according to the selection criteria after completing the pre-screening questionnaire will be scheduled after reading and signing the consent form (2 copies). During the second visit, all clinical and neurological assessments will be performed before and after tDCS stimulation phase. Each patient will be clinically and neurologically assessed before and after the stimulation, allowing data to be collected 4 times (T0, T1, T2, and T3).
tDCS protocol: Group Real tDCS: The participant will receive anodal tDCS over the left DLPFC and the reference electrode will place over the right forearm. The stimulation intensity will be 2mA DC delivered for 20 min (30 s step-up ramp, 30 s step-down ramp), repeated six times, during two weeks (Mon, Wed, Frid).
Group sham tDCS: Identical to the real tDCS, except the participants will only receive the initial 30 seconds of ramp-up, after which the current will be set to 0 for the remainder of the 20 minutes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Crossover Assignment
| Arm | Type | Receives |
|---|---|---|
| Real tDCS | Active comparator | Device: transcranial direct current stimulationThe participant will receive anodal tDCS for 20 min at an intensity of 2 mA while seated comfortably and quietly in a room. The intensity will start at 0 mA and will be incrementally increased to 2mA over the initial 30 seconds. At the 19:30 minute time point, the current will gradually be reduced from 2 mA to 0 mA. |
| Sham tDCS | Sham comparator | Device: transcranial direct current stimulationIdentical to the real tDCS, except the participants will only receive the initial 30 seconds of ramp-up, after which the current will be set to 0 for the remainder of the 20 minutes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient diagnosed with painful diabetic peripheral neuropathy (PDPN) components with DN4 score ≥ 4/10, and chronic pain with an intensity of at least VAS> 4/10.
- Onset of neuropathic PDPN pain for at least 6 months.
- Pain intensity as measured by VAS> 4/10 in the week preceding inclusion in the study.
- drug-resistant patients who have no pain reduction of 50% or an improvement of at least 2 points in the Patient Global Impression of Change, having used all the classes of drugs indicated as a first, second or third line.
- Absence of glycemic de-compensation with HbA1c values <9% in the previous 6 months.
Key exclusion criteria (8 listed)
- Neurological comorbidities.
- Presence of contraindications to the use of electrotherapy (pacemaker, epilepsy, etc ...).
- Pregnancy.
- Previous neurosurgical interventions.
- psychiatric conditions.
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 |
|---|---|---|
| transcranial direct current stimulationTranscranial direct current stimulation (tDCS) is a noninvasive technique of neuronal modulation that has been used in different neurological conditions, neuropathic pain. | Device | Real tDCS, Sham tDCS |
Primary outcome
Changes in Pain severity
Time frame: Measured at baseline and immediately after the intervention
Changes in Pain severity will be measured by Brief Pain Inventory (BPI) to determine the effect of anodal Transcranial direct current stimulation (tDCS) in reducing pain of subjects with pain associated with diabetic neuropathy.
7 secondary outcomes
Changes in Depression severity
Time frame: Measured at baseline and immediately after the intervention
Changes in Anxiety severity
Time frame: Measured at baseline and immediately after the intervention
Changes in sleep quality
Time frame: Measured at baseline and immediately after the intervention
Changes in Quality of Life
Time frame: Measured at baseline and immediately after the intervention
Changes in Pain related to disability
Time frame: Measured at baseline and immediately after the intervention
Changes in Pain Catastrophizing
Time frame: Measured at baseline and immediately after the intervention
Changes in Neuropathic Pain Symptom
Time frame: Measured at baseline and immediately after the intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2021.
- Background: PubMed 8469345Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O'Brien PC, Melton LJ 3rd, Service FJ. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993 Apr;43(4):817-24. doi: 10.1212/wnl.43.4.817.
- Background: PubMed 27999003Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-154. doi: 10.2337/dc16-2042. No abstract available.
- Background: PubMed 15673800Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH; EURODIAB Prospective Complications Study Group. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005 Jan 27;352(4):341-50. doi: 10.1056/NEJMoa032782.
- Background: PubMed 20876709Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303.
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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.
Slivia Natoli, MD, PhD study director
Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcranial direct current stimulation in people with Diabetic Neuropathies and Chronic Pain, run by University of Rome Tor Vergata at 1 site in Italy.
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 6 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 10 Aug 2021. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Silvia Natoli, MD, PhD (+393451690925, silvia.natoli@uniroma2.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Pain severity (time frame: Measured at baseline and immediately after the intervention). 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 NCT04306289, which also lists 15 linked publications.
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 10 Aug 2021.