tDCS Associated With Peripheral Electrical Stimulation for Pain Control in Individuals With Sickle Cell Disease

NCT ID: NCT02813629

Last Updated: 2018-09-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2022-12-31

Brief Summary

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So far, no study investigated the safety and efficacy analgesic of transcranial direct current stimulation (tDCS) associated to peripheral electrical stimulation (PES) in individuals with SCD who suffer from chronic pain. Several studies have reported a decrease in O²Hb concentration in the regions below the electrodes and in other cortical areas during anodic or cathodic tDCS, which implies a risk factor for vasoocclusive events in individuals with SDC due to polymerization of hemoglobin when exposed to these low O²Hb concentrations. For this reasion, the aim main of this study is to assess the effect of a single session of transcranial direct current stimulation (tDCS) associated to peripheral electrical stimulation (PES) on safety and efficacy analgesic in individuals with sickle cell disease (SCD). Others aims sencondaries are evaluate the effect of a single session of transcranial direct current stimulation (tDCS) associated to peripheral electrical stimulation (PES) on biomarkers neurophysiological and inflammatory.

Detailed Description

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Pain, in its various manifestations, is the symptom most often associated to SCD, being responsible for over 90% of hospital admissions. Oftenly pain has a major impact on the patient's life and is associated with some degree of disability. Chronic pain may reflect the continuity of tissue injury and central nervous system maladaptive plasticity. They start with tissue injuries such as leg ulcers, avascular osteonecrosis, chronic osteomyelitis, arthropathy, or even continue after the repair process, by central nervous sensitization and / or peripheral. The lack of diagnosis in cases of chronic and neuropathic pain in patients with SCD is common, implying inappropriate use of therapeutic resources by the health services, resulting in increased suffering to the patient. The release of inflammatory mediators is related to the perception of pain, and may cause nociceptor sensitization.

The tDCS has the potential to change the neuronal membrane resting potential, this effect is dependent on the polarity, being that cathode produces hyperpolarization, whereas anode produces depolarization, in this way can induce an effect of inhibition and facilitation of neuronal firing, respectively. This effects can induces changes in cortical excitability. Although tDCS may modulate areas related to endogenous pain control, its effects seem to be diffuse, and focality would probably enhance its effects. The peripheral electrical stimulation (PES), in another way, may also modulate cortical excitability, depending mainly on its amplitude and frequency. PES modulation of cortical excitability is very focal, occurring only in the stimulated region. The combination of these two neuromodulatory techniques has showed additive effects in some studies with individuals suffering from chronic pain,which promoting a general effect (tDCS), and the other a more focal effect (TENS). Although this additive effect has been demonstrated, to date, no study evaluate its safety and efficacy in individuals with DF.

As a secondary outcome, the investigators are going to access the influence of the intervention on quantitative electroencephalography (qEEG). Growing evidence points out to different brain characteristics between individuals with chronic pain and healthy. qEEG has high temporal resolution and evaluates primary electrical effects of neural excitation, allowing identify possible patterns of brain functioning in individuals with chronic pain. qEEG allowed the identification of the thalamocortical dysrhythmia (TCD) in patients with chronic pain characterized by an increased low frequency band power density theta (4 - 7Hz) and a decrease in high frequency bands alpha (8 -12Hz) and beta (13 - 30Hz). This dysrhythmic mechanism may occur from the periphery to the thalamus (bottom-up) or cortical dysregulation (top-down), disinhibition of the thalamus. This process results in hyperpolarization of thalamic neurons, leading to a preponderance of low frequency oscillations in qEEG. The persistence thalamic firing at low frequencies can lead to a collateral inhibition in cortical regions around, which could theoretically lead to a decrease in the higher frequencies. This increase occurs at low frequency regions involved in neuro matrix of pain.

The investigators will alse avaluate the influence of the chronic pain sencondary to avascular necrosis of hip joint about cortical motor reorganization using transcranial magnetic stimuation (TMS). Recent data point to a gluteus maximus muscle weakness during maximal voluntary contraction in pronation position in individuals with joint pain in the hip. Similarly, individuals with legg calve perthes who suffer from femoral head necrosis, weakness of the abductor hip musculature was related to poor clinical outcomes. A possible explanation for these findings is cortical motor reorganization, which is associated with motor control impairment, and this has been demonstrated in individuals with chronic lateral epicondylalgia and knee osteoarthritis, where cortical organization is altered and correlated positively with the time of Pain and is associated with the perpetuation of pain. This cortical reorganization can occur in the somatotopic areas corresponding to the motor or sensorial homunculus, having as characteristic an overlap, retraction and "blurring" in the somatotopic representation of a certain region.

The mediators released by cells of the immune and inflammatory system can act directly on neurons sensitizing and enabling them (usually peripheral nociceptors or neurons in the dorsal horn of the spinal cord). There are several mediators in a long and growing list that includes cytokines and neurotrophins.The major cytokines in an acute inflammation are the Tumor Necrosis Factor (TNF) and the interleukins (IL-1), IL-6 and IL-8, which are important mediators of acute and chronic inflammatory reactions, as well as processes of repair and resolution. High serum levels of IL-8 have been observed in patients in vase-occlusive crisis, important clinical aspect of the pathogenesis of SCD. The presence of the mutant allele A appears to influence the expression of the TNF-alpha, being the AA genotype considered a high producer.

Neurotrophins are dimeric proteins that are essential for the normal development of the nervous system in vertebrates. This family includes the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and other neurotrophins (NT). Currently, it is recognized that certain neurotrophins, particularly the NGF and the brain-derived neurotrophic factor BDNF play a significant role in nociception, so that the NGF sensitizes nociceptors at the periphery, while the BDNF enhances the response ability of the dorsal horn neurons of the spinal cord. The BDNF gene, which encodes the BDNF protein, located on chromosome 11 at the boundary of regions 11p13 and 11p14 of the human genome has been investigated in a wide range of areas related to neuroplasticity, including differences in brain morphology, learning and memory, interactions with brain stimulation protocols of plasticity induction and recovery after brain injury and has been associated with a wide variety of neurological disorders, including, for example, depression, schizophrenia and attention deficit hyperactivity disorder (ADHD).

Conditions

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Anemia, Sickle Cell Chronic Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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SS-tDCS (active) plus PES (active)

tDCS plus PES (n=15).

Group Type ACTIVE_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SS-tDCS (active) plus PES (simulated)

tDCS plus PES (n=15).

Group Type ACTIVE_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SS-tDCS (simulated) plus PES (active)

tDCS plus PES (n=15).

Group Type ACTIVE_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SS-tDCS (simulated) plus PES (simulated)

tDCS plus PES (n=15).

Group Type SHAM_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SC-tDCS (active) plus PES (active)

tDCS plus PES (n=15).

Group Type ACTIVE_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SC-tDCS (active) plus PES (simulated)

tDCS plus PES (n=15).

Group Type ACTIVE_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SC-tDCS (simulated) plus PES (active)

tDCS plus PES (n=15).

Group Type ACTIVE_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

SC-tDCS (simulated) plus PES (simulated)

tDCS plus PES (n=15).

Group Type SHAM_COMPARATOR

tDCS plus PES

Intervention Type DEVICE

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

Interventions

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tDCS plus PES

transcranial direct current stimulation (tDCS) uses a pair of electrodes and sponges soaked in saline solution placed over specific regions of the head to polarize neurons and produce changes in resting membrane potentials. This changes may increase or decrease neuronal excitability and produce diverse clinical effects, including analgesia.

PES uses also a pair of electrodes over specific regions of the body to promote neuronal action potentials in peripheral nerves. PES over motor threshold increases cortical excitability, and at the sensory threshold decreases excitability.

Intervention Type DEVICE

Other Intervention Names

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transcranial direct current stimulation (tDCS) peripheral electrical stimulation (PES)

Eligibility Criteria

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Inclusion Criteria

* Being diagnosed with sickle cell disease hemoglobin electrophoresis.
* Be aged 18 years old to 50 years old.
* Having signed the consent form and clarified.
* Having chronic pain with at least 3 months duration.
* Being diagnosed with femoral head osteonecrosis
* Have more than one type of chronic pain.

Exclusion Criteria

* Have cochlear implants, pacemakers or metallic implant in the skull / brain;
* Have metallic implant application site of peripheral stimulation;
* History of head trauma;
* Pregnancy;
* seizures or epilepsy History;
* Being in drug use that modify neuronal activation threshold (eg antidepressants and anticonvulsants);
* Having diagnosis of fibromyalgia, or any impairment to be confused with the symptoms of SCD;
* Have pain confirmed neuropathic type.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Federal University of Bahia

OTHER

Sponsor Role collaborator

Faculdade Adventista da Bahia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Abrahão F Baptista, Prof.

Role: PRINCIPAL_INVESTIGATOR

Federal University of Bahia

Wellington S Silva, Prof.

Role: STUDY_DIRECTOR

Faculdade Adventista da Bahia

Locations

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Functional Electrical Stimulation Laboratory

Salvador, Estado de Bahia, Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Abrahão F Baptista, Prof.

Role: CONTACT

55 11 98830-3941

Tiago S. Lopes, Sr

Role: CONTACT

55 75 99963-6349

Facility Contacts

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Abrahão F Baptista, Prof.

Role: primary

55 71 3283-8906

References

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Other Identifiers

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31237514.1.0000.0042

Identifier Type: -

Identifier Source: org_study_id

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