tDCS and Pain Associated With Diabetic Neuropathy

NCT ID: NCT04306289

Last Updated: 2021-08-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-09-01

Brief 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. 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.

Conditions

Diabetic Neuropathies; Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Real tDCS

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.

Group Type: ACTIVE_COMPARATOR

transcranial direct current stimulation

Intervention Type: DEVICE

Transcranial direct current stimulation (tDCS) is a noninvasive technique of neuronal modulation that has been used in different neurological conditions, neuropathic pain.

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.

Group Type: SHAM_COMPARATOR

transcranial direct current stimulation

Intervention Type: DEVICE

Transcranial direct current stimulation (tDCS) is a noninvasive technique of neuronal modulation that has been used in different neurological conditions, neuropathic pain.

Interventions

transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a noninvasive technique of neuronal modulation that has been used in different neurological conditions, neuropathic pain.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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%.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rome Tor Vergata

OTHER

Sponsor Role: lead

Responsible Party

Mohammad Alwardat

postdoctoral fellowship

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Slivia Natoli, MD, PhD

Role: STUDY_DIRECTOR

Department of Clinical Science and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.

Locations

Prof. Silvia Natoli

Rome, Lazio, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Silvia Natoli, MD, PhD

Role: CONTACT

silvia.natoli@uniroma2.it

+393451690925

Antonio Pisani, MD, PhD

Role: CONTACT

pisani@uniroma2.it

+393204311363

Facility Contacts

Silvia Natoli, MD, PhD

Role: primary

silvia.natoli@uniroma2.it

+393451690925

Mohammad Alwardat, PT, PhD

Role: backup

wardatm1@gmail.com

+393296423074

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Other Identifiers

University of Rome Tor Vergata

Identifier Type: -

Identifier Source: org_study_id