THE EFFECT OF tDCS IN THE TREATMENT OF CHRONIC PELVIC PAIN ASSOCIATED WITH ENDOMETRIOSIS (tDCS)

THE EFFECT OF TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS) IN THE TREATMENT OF CHRONIC PELVIC PAIN ASSOCIATED WITH ENDOMETRIOSIS

The purpose of this study is to determine if transcranial direct current stimulation (tDCS) is effective in the treatment of chronic pelvic pain associated with endometriosis

Study Overview

• Status: Unknown
• Conditions: Chronic Pain; Endometriosis
• Intervention / Treatment: Device: transcranial direct current stimulation (tDCS); Device: Sham Transcranial Direct Current Stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wolnei Caumo, MD, PhD; Phone Number: 51 3359 8083; Email: caumo@cpovo.net

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre
      • Contact: Wolnei Caumo, MD, PhD; Phone Number: (51) 3359 8083; Email: caumo@cpovo.net
      • Principal Investigator: Wolnei Caumo, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• age > 18 years old, non-menopausic, with the diagnosis of endometriosis by videolaparoscopy and biopsy, able to understand and write the Portuguese language, in treatment with isolated progestin for at least one month, that have worst daily pain in the analogue visual scale > 4 cm in most of the days in the last month

Exclusion Criteria:

• left-handed women, endometriosis implantation in intestine, bladder or urether (surgical treatment indication), history of intense or frequent headache, chronic dermatologic disease, previous adverse effects to treatment with tDCS, seizures, severe cranial trauma with alteration of the cranial anatomy, metallic intracranial implants or pacemaker, history of pelvic inflammatory disease, non-compensated psychiatric disease, non-collaborative patients, history of neurologic, oncologic disease, heart, renal or hepatic failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active tDCS; tDCS will be applied in the head of the patients in 20 minute sessions, daily from Monday to Friday for 2 weeks (10 sessions total). The stimulation will be administered with a pair of surface electrodes, sponge coated, soaked in saline. A battery-powered constant current stimulator will be used for this purpose (tDCS device Soterix 1X1). The stimulation is performed by placing the anodal electrode in the primary motor cortex (M1) and the cathodal one in the contralateral supraorbital area, and it will use a 2 mA current.	Device: transcranial direct current stimulation (tDCS); The stimulation will be administered with a pair of surface electrodes, sponge coated, soaked in saline. A battery-powered constant current stimulator will be used for this purpose (tDCS device Soterix 1X1). The stimulation is performed by placing the anodal electrode in the primary motor cortex (M1) and the cathodal one in the contralateral supraorbital area and it will use a 2 mA current.; Other Names: tDCS
Sham Comparator: tDCS Sham; The sham tDCS consists of the same montage of the active tDCS, but the device is turned off 30 seconds after initiating stimulation (without letting the patient notice it). Rest of the montage is kept identical as the active one during the 20 minutes that the session lasts.	Device: Sham Transcranial Direct Current Stimulation; The sham tDCS consists of the same montage of the active tDCS, but the device is turned off 30 seconds after initiating stimulation (without letting the patient notice it). Rest of the montage is kept identical as the active one during the 20 minutes that the session lasts.; Other Names: Sham tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in worst daily pain assessed with the visual analogue scale.	Patients will be asked to daily write down their worst pain level (assessed by the Visual Analogue Scale, self-administered) in a paper diary with different scores: global pain, pain during menses, pain during sexual intercourse, pain during urination, pain during defecation. They will also be asked to daily write the analgesic drug intake. Total evaluations: 35 days.	Once Daily. Start 7 days before treatment, everyday during treatment period and every day during follow-up period (total = 35 days)
Changes in motor cortex blood flow assessed by near infrared spectroscopy	Motor cortex blood flow will be assessed before the first session of tDCS (on Treatment day 1), after the end of treatment period (Day 15) and after the follow-up period (Day 29). Total = 3 evaluations.	Treatment Day 1 (before receiving the 1st session of tDCS); Day 15 (at the end of treatment period) and Day 29 (at the end of follow-up period)
Change in Functional Pain Scale	Functional Pain Scale will be assessed by the Brazilian Profile of Chronic Pain: Screen (B-PCP:S) once a week, as folow: On the Treatment Day 1 (before the first session of tDCS - considered baseline), on Treatment Day 8, Day 15, Day 22 and Day 29. Total = 5 evaluations.	Once a week - Treatment Day 1, Day 8, Day 15, Day 22, Day 29
Change in the temperature pain threshold	It will be assessed by the Quantitative Sensory Test (QST) in the dominant (right) forearm. The heat pain tolerance and pain threshold to the heat and the temperature defined as pain 6/10 by the participant. The temperature starts at 32°C, and it heat at a 1.0 °C/sec rate and cools down after a button is pressed or whenever it reaches the max temperature of 52°C. The participant will be asked to press the button at the first sensation of pain to determine the pain threshold; to press the button whenever she can not stand the heat anymore for the pain tolerance determination and, for last, to press the button at the temperature she fells pain equivalent to 6/10 in the numeric scale of pain. The pain threshold and the temperature of pain 6/10 will be determined by the arithmetic mean of 3 evaluations each. Total of 3 test days: Day 1 (before the first session of tDCS), after the end of the Treatment period (Day 15) and at the end of the follow-up period (Day 29).	up to Day 29
Change in effect of the descendent modulator system of pain	It will be assessed by the Conditioned Pain Modulation test (CPM). A nociceptive tonic conditioning stimulus - immersion of the non-dominant hand in cold water (0°C for 1 minute) - will be applied concomitant to the progressive thermal stimulus in the dominant forearm as applied in the QST pattern until it reaches the 6/10 pain temperature previously determined by the participant. It will be tested in Treatment Day 1 (before the first session of tDCS - considered baseline), after the end of the Treatment period (Day 15) and at the end of the follow-up period (Day 29) - Total = 3 evaluation.	up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum biomarkers level: The brain derived neurotrophic factor (BDNF) and interleukins	A blood sample will be colected to measure BDNF and interleukins on Treatment Day 1 (right before the first tDCS session - considered baseline), after the end of the treatment period (day 15) and after the end of the follow-up period (day 29). Total = 3 evaluations	up to Day 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive symptoms level	Depression symptoms will be assessed by using the Beck II Inventory. It will be assessed before the first session of tDCS (on Treatment day 1), after the end of treatment period (Day 15) and after the follow-up period (Day 29). Total = 3 evaluations.	Treatment Day 1 (before receiving the 1st session of tDCS); Day 15 (at the end of treatment period) and Day 29 (at the end of follow-up period)
Anxiety level	Anxiety level will be assessed by State-Trait Anxiety Inventory (STAI), adapted to Brazilian Portuguese Language. It will be assessed before the first session of tDCS (on Treatment day 1), after the end of treatment period (Day 15) and after the follow-up period (Day 29). Total = 3 evaluations.	Treatment Day 1 (before receiving the 1st session of tDCS); Day 15 (at the end of treatment period) and Day 29 (at the end of follow-up period)
Psychiatric diseases	Psychiatric diseases will be evaluated by the Structured Clinical Interview for DSM-IV (SCID) in the patient screening. Total = 1 evaluation	1day on patient screening
Estradiol level	Estradiol blood level will be measured on treatment Day 1 (before receiving the 1st session of tDCS). Total = 1 evaluation	Treatment Day 1 (before receiving the 1st session of tDCS)
Adverse Effects	At the end of each tDCS session, the incidence of any adverse effects - paresthesia, headache, dizziness, nausea, neck pain, burns, redness or pain in the scalp, insomnia, abrupt humor changes and lack of concentration - will be questioned to the participant. Total = 10 evaluations	up to Day 29
Pain catastrophizing thoughts	The level of catastrophic thinking will be assessed by the Pain Catastrophizing Scale on Treatment Day 1 (before receiving the 1st session of tDCS), after the treatment period (Day 15) and at the end of the follow-up period (Day29). Total = 3 evaluations	Treatment Day 1 (before receiving the 1st session of tDCS); Day 15 (at the end of treatment period) and Day 29 (at the end of follow-up period)
Demographic data and comorbidities	Demographic data and comorbidities will be asked in the baseline (before the first session of tDCS). Total = 1 evaluation.	Baseline
Change in quality of life	Quality of life will be assessed by the WHOQOL (World Health Organization Quality of Life), in Treatment Day 1 (before the first session of tDCS - considered baseline) and after the treatment period (Day 15). Total = 2 evaluations	Baseline and Day 15

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Wolnei Caumo, MD, PhD, Hospital de Clinicas de Porto Alegre

Publications and helpful links

General Publications

• Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.
• Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulation--technical, safety and functional aspects. Suppl Clin Neurophysiol. 2003;56:255-76. doi: 10.1016/s1567-424x(09)70230-2. No abstract available.
• Boros K, Poreisz C, Munchau A, Paulus W, Nitsche MA. Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humans. Eur J Neurosci. 2008 Mar;27(5):1292-300. doi: 10.1111/j.1460-9568.2008.06090.x. Epub 2008 Feb 29.
• Caumo W, Ruehlman LS, Karoly P, Sehn F, Vidor LP, Dall-Agnol L, Chassot M, Torres IL. Cross-cultural adaptation and validation of the profile of chronic pain: screen for a Brazilian population. Pain Med. 2013 Jan;14(1):52-61. doi: 10.1111/j.1526-4637.2012.01528.x. Epub 2012 Nov 21.
• Sehn F, Chachamovich E, Vidor LP, Dall-Agnol L, de Souza IC, Torres IL, Fregni F, Caumo W. Cross-cultural adaptation and validation of the Brazilian Portuguese version of the pain catastrophizing scale. Pain Med. 2012 Nov;13(11):1425-35. doi: 10.1111/j.1526-4637.2012.01492.x. Epub 2012 Oct 4.
• Valle A, Roizenblatt S, Botte S, Zaghi S, Riberto M, Tufik S, Boggio PS, Fregni F. Efficacy of anodal transcranial direct current stimulation (tDCS) for the treatment of fibromyalgia: results of a randomized, sham-controlled longitudinal clinical trial. J Pain Manag. 2009;2(3):353-361.
• Nacul AP, Spritzer PM. [Current aspects on diagnosis and treatment of endometriosis]. Rev Bras Ginecol Obstet. 2010 Jun;32(6):298-307. doi: 10.1590/s0100-72032010000600008. Portuguese.
• Fenton BW, Palmieri PA, Boggio P, Fanning J, Fregni F. A preliminary study of transcranial direct current stimulation for the treatment of refractory chronic pelvic pain. Brain Stimul. 2009 Apr;2(2):103-7. doi: 10.1016/j.brs.2008.09.009. Epub 2009 Feb 28.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): May 1, 2015
• Study Completion (Anticipated): May 1, 2016

Study Registration Dates

• First Submitted: June 10, 2014
• First Submitted That Met QC Criteria: June 10, 2014
• First Posted (Estimate): June 11, 2014

Study Record Updates

• Last Update Posted (Estimate): June 11, 2014
• Last Update Submitted That Met QC Criteria: June 10, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: tDCS; Transcranial Direct Current Stimulation; Endometriosis; Near Infrared Spectroscopy; Chronic Pelvic Pain; NIRS
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Endometriosis; Pelvic Pain
• Other Study ID Numbers: 14-0092