Neuroplasticity:Melatonin and Transcranial Current Stimulation in Healthy Subjects.

Effect of Melatonin and Transcranial Direct Current Stimulation (tDCS) on Neuroplasticity and the Heat-pain Detection Threshold in Healthy Subjects:Randomized, Double-blind,Crossover Trial

Pain exerts a tremendous cost in healthy care, rehabilitation and lost productivity. It is is associated with a wide range of diseases and their social consequences is a public health problem.

With the progress of neuroscience and studies on the plasticity of the central nervous system, it has been provided a better understanding of the neurobiological mechanisms of pain.

The neurohormone Melatonin stands by having systemic and diverse mechanisms of action, both in physiological and pathological situations, with modulating effects on the process of nociceptive signaling and neurochemical mechanisms such as serotonergic, opioidergic and GABAergic, exerting anti-inflammatory action, analgesic activity among others.

The advent of neuromodulation techniques such as transcranial direct current stimulation (tDCS), which promote changes in neuronal activity and signaling to be effective in conditions of chronic pain by attenuating changes in cortical excitability.

There is clinical evidence of the analgesic effect of Melatonin and tDCS alone. Thus, considering the potential for each isolated intervention and the lack of knowledge of their combined effect, the authors propose the present study to investigate the effect of this combination on the heat-pain detection threshold and the neuroplasticity in the healthy subjects.

Study Overview

• Status: Unknown
• Conditions: Pain; Analgesia Disorder
• Intervention / Treatment: Drug: Melatonin; Device: Transcranial Direct Current Stimulation (tDCS)

Detailed Description

The methods are according to the CONSORT guidelines.

Heat pain threshold and tolerance : Quantitative Sensory Testing (QST) will be used on a computer Peltier-based device thermode.

Conditioned Pain Modulation (CPM)-task: Immerssing the non-dominant hand cold water for 1 minute.

Serum Brain Derived Neurotrophic Factor (BDNF).

Transcranial Magnetic Stimulation (TMS) assessment: motor threshold, motor evoked potential, Short intracortical inhibition and intracortical facilitation.

Statistical analyses: Descriptive statistics, Linear and multiple regression analysis, performed with SPSS version18.0.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 900035-903
      • Recruiting
      • Hospital de Clínicas de Porto Alegre
      • Contact: Wolnei Caumo; Phone Number: 555133590083; Email: caumo@cpovo.net
      • Sub-Investigator: Nadia Jardim, MD, Msc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male 18-40 years old
• Healthy
• Without medication
• Sign the informed consent

Exclusion Criteria:

• Patients who did not understand the Portuguese
• Acute or chronic pain conditions
• Medical or psychiatric disorders
• History of alcohol or substance abuse
• Neurological disorder
• Use of medications affect in the central nervous system
• Traumatic brain injury
• Neurosurgery
• Metallic implant in the brain

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Melatonin; 0,25mg/Kg sl before tDCS	Drug: Melatonin
Experimental: tDCS; Transcranial direct current stimulation once time. Dose 2 mA, 20 seconds.	Device: Transcranial Direct Current Stimulation (tDCS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in heat-pain threshold with pain score	Heat-threshold by Pettier-based device on the contralateral hand assessment pain score (VAS)	Baseline, one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Brain-Derived neurotrophic factor (BDNF)		Baseline, one week
Change from Baseline from Catastrophizing Scale		Baseline, one week
Change from baseline Inventory of state-trait anxiety Scale		Baseline, one week
Change from baseline Inventory of Coping		Baseline, one week
Change from baseline of cortical excitability	Transcranial Magnetic Stimulation (TMS) assessment motor threshold, motor-evoked potentials, silent period, intracortical inhibition and facilitation	Baseline, one week

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Wolnei Caumo, Hospital de Clinicas de Porto Alegre - UFRGS

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): August 1, 2014

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: July 18, 2014
• First Posted (Estimate): July 21, 2014

Study Record Updates

• Last Update Posted (Estimate): July 21, 2014
• Last Update Submitted That Met QC Criteria: July 18, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Pain; Melatonin; Transcranial Direct Current Stimulation; Neuroplasticity; Analgesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 130155

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No