LDN and tDCS in Fibromyalgia

Fibromyalgia Clinical Trial

Official title:

Association of Low Doses of Naltrexone and Transcranial Direct Current Stimulation in Fibromyalgia: Randomized Clinical Trial, Blind, Controlled With Placebo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04502251
• Other study ID #: 70005317.5.0000.5307
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 1, 2018
• Est. completion date: July 1, 2020

Study information

• Verified date: August 2020
• Source: Centro Universitario La Salle
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Fibromyalgia is a complex generalized and diffuse musculoskeletal chronic pain; and pharmacological approaches are widely used to relieve pain and increase life quality. In this context, low-dose naltrexone (LDN) was able to increase nociceptive threshold in patients with fibromyalgia. Moreover, non-pharmacological techniques, like Transcranial Direct Current Stimulation (tDCS), have been shown effective for pain management. This study aims to evaluate the analgesic and neuromodulatory effect of combined LDN followed by tDCS in fibromyalgia patients. This is a randomized, double-blinded, parallel, placebo/sham-controlled trial, in which 92 (10% loss) women with fibromyalgia will be included included and signed the informed consent. Patients will be allocated into 4 groups: tDCS+LDN (n=21), Sham-tDCS+LDN (n=22), tDCS+Placebo (n=22), and Sham-tDCS+Placebo (n=21). LDN or placebo (p.o.) intervention lasts 26 days, in the last five, tDCS will be applied (sham or active, 20min, 2mA). Questionnaires assessed are: Sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Chronic Pain Profile Scale (CPP). Also, pain measures were taken: Pain Pressure Threshold (PPT) and Conditioned Pain Modulation (CPM). Blood samples will be collected to analyze Brain Derived Neurotrophic Factor (BDNF) serum levels.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: July 1, 2020
• Est. primary completion date: August 1, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 8 Years to 65 Years

Eligibility

Inclusion Criteria:

• signed the consent form

• women from 18 to 65 years

• confirmed diagnosis of fibromyalgia according 2016 American College of Rheumatology criteria

• read and write

• pain higher than 6 in the Visual Analogue Scale (VAS), in the last 3 months

• chronic stable treatment in the last 3 months.

Exclusion Criteria:

• in use of opioid drugs;

• pregnancy or not using anticontraceptive

• history of alcohol or drug abuse in the last 6 months

• history of neurological pathologies

• history of arrhythmia

• history of use of drugs that might change vascular response

• history of head trauma

• history of neurosurgery

• decompensated systemic diseases or chronic inflammatory diseases (lupus, rheumatoid arthritis, Sjogren syndrome, Reiter syndrome)

• history of non-compensated hypothyroidism

• personal history of cancer.

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

Drug:
• Low-Dose Naltrexone
4.5mg daily dose, orally, during 26 days

Device:
• Transcranial Direct Current Stimulation
An anodal electrode was placed on the scalp above the primary motor cortex (M1), contralateral to the dominant cortex. The cathodal electrode was placed on the supraorbital contralateral area. The current used was 2mA during 20 minutes.

Drug:
• Placebo
The capsule presented the same format, size and color as LDN capsules, however the excipient used was starch.

Device:
• Sham Transcranial Direct Current Stimulation
Sham-tDCS stimulation consists of an active current during 30 seconds

Locations

Country	Name	City	State
Brazil	Universidade La Salle	Canoas	Rio Grande Do Sul

Sponsors (2)

Lead Sponsor	Collaborator
Centro Universitario La Salle	Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

References & Publications (35)

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Fregni F, Boggio PS, Nitsche M, Bermpohl F, Antal A, Feredoes E, Marcolin MA, Rigonatti SP, Silva MT, Paulus W, Pascual-Leone A. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Exp Brain Res. 2005 Sep;166(1):23-30. Epub 2005 Jul 6. — View Citation

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Khedr EM, Omran EAH, Ismail NM, El-Hammady DH, Goma SH, Kotb H, Galal H, Osman AM, Farghaly HSM, Karim AA, Ahmed GA. Effects of transcranial direct current stimulation on pain, mood and serum endorphin level in the treatment of fibromyalgia: A double blinded, randomized clinical trial. Brain Stimul. 2017 Sep - Oct;10(5):893-901. doi: 10.1016/j.brs.2017.06.006. Epub 2017 Jun 23. — View Citation

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Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F. Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci. 2003 May 15;15(4):619-26. — View Citation

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain in VAS	Visual Analogue Scale (VAS) that goes from 0 cm (without pain) to 10cm (worst pain).	Change between baseline and after association (26 days from baseline)
Secondary	Depressive symptoms	Beck Depression Inventory (BDI-II) that goes from 0 (without depressive symptoms) to 63 (worst depressive symptoms)	Change between baseline and after association (26 days from baseline)
Secondary	Anxiety levels	State-Trait Anxiety Inventory (STAI) divided into state anxiety (from 0 to 52, the higher the worse) and trait anxiety (from 0 to 48, the higher the worse)	Change between baseline and after association (26 days from baseline)
Secondary	Pain Catastrophizing Thought	Pain Catastrophizing Scale (PCS): divided into rumination (from 0 to 16, the higher the worse), magnification (from 0 to 12, the higher the worse) and hopelessness (from 0 to 24, the higher the worse). Total goes from 0 to 52, the higher the worse	Change between baseline and after association (26 days from baseline)
Secondary	Profile of Chronic Pain	Profile of Chronic Pain Scale (PCP:S): divided into Frequency and Intensity of Pain (from 0 to 30, the higher the worse), Pain Effect in Activities (from 0 to 36, the higher the worse) and Pain Effect in Emotions (from 0 to 25, the higher the worse)	Change between baseline and after association (26 days from baseline)
Secondary	Pain Pressure Threshold	Pain Pressure Threshold (PPT) measured using an electronic algometer applied in the right forearm; and patients need to report the first pain sensation (minimum pain) and maximum pain. Threshold goes from 0 to the maximum value the patient can hold, the higher the value, better is the result	Change between baseline and after association (26 days from baseline)
Secondary	Conditioned Pain Modulation	Conditioned Pain Modulation (CPM) with an algometer (PPT task), the patient informed when felt a pain equal to 6 in the VAS. This pain level was applied in the right forearm for 30 seconds, while the left forearm (non-dominant hand) was submerged in water from 0°C to 1.5°C; after 30s, patients reported their pain in each of the arms. CPM = left forearm VAS - 6. (from -4 to 6, the value must be as closest to -4 as possible, meaning the higher the worse)	Change between baseline and after association (26 days from baseline)
Secondary	Serum BDNF	Blood sample collected and centrifuged, the supernatant aliquoted for BDNF analysis using ELISA technique, according to manufacturer's instructions (values start in 0, patients with fibromyalgia usually have higher levels of serum BDNF, therefore the higher the worse)	Change between baseline and after association (26 days from baseline)