Brain Response to Single Dose of Pregabalin in Fibromyalgia

NCT02639533 | Completed Phase 2

• 1 other identifier: 14-0624
• Study Type: interventional
• Target: 27
• Locations: 0 countries
• Sites: N/A

Brief Summary

Fibromyalgia syndrome represents a "spectrum disorder" characterized by widespread chronic pain, fatigue, sleep disturbances, mood and cognitive alterations. The most accepted models explaining the causes of the disease have focused on the reduced pain inhibitory systems activity, that allow low intensity stimuli to be processed easier, and that finally amplify pain stimuli. One of the interventions approved for Fibromyalgia is Pregabalin, which demonstrated to be effective reducing pain. Different studies in animals have shown that it works reducing the liberation of neuronal messengers, which slow the conduction of pain signals. Although studies in humans have confirmed Pregabalin clinical benefits, there are still few studies aiming to explain how it actually works in patients with fibromyalgia, though. A better understanding of the mechanisms by which Pregabalin reduces pain in patients with fibromyalgia would allow designing new interventions to enhance its clinical effects. Thus, the investigators propose to study in real-time the electrical, vascular and hormonal response of the brain of patients with fibromyalgia who receive a single dose of Pregabalin. The vascular response will be assessed using functional near infrared spectroscopy (fNIRS) neuroimaging techniques. The electrical response will be assessed using Transcranial Magnetic Stimulation (TMS). The hormonal response will be assessed in blood, measuring neurotrophins (Brain Derived Neurotrophic Factor) and inflammatory mediators (Tumor Necrosis Factor). These responses will be studied in consideration of the patients' characteristics that will be assessed using validated scales. Taken into account the above considerations, a crossover, double-blinded randomized clinical trial is proposed. In the investigators' study, patients and healthy volunteers will be asked to visit the investigators' laboratory in three opportunities: one for a baseline assessment, and the other two to test the effects of either Pregabalin 150 mg PO or Placebo. All participants will eventually receive both, Pregabalin and Placebo. In each visit a brain hemodynamic, electrical, hormonal and clinical evaluation will be performed.

Conditions

Fibromyalgia

Keywords

fibromyalgia; pregabalin; cortical excitability; functional near infrared spectroscopy

Outcome Measures

Primary Outcomes (2)

• Cortical Excitability: Intracortical Inhibition.

  Cortical excitability parameters assessed non-invasively using paired-pulse Transcranial Magnetic Stimulation. Intracortical inhibition will be assessed using a conditioning stimuli of 80% of the motor threshold (MT) and a testing pulse of 120% the of the MT, with interstimuli interval (isi) of 2 and 4 microseconds. The Intracortical Inhibition corresponds to the ratio between the resultant potential and the motor evoked potential.

  1 hour after intervention

• Cortical hemodynamics: Oxy-hemoglobin concentration (mM/L)

  Cortical hemodynamics assessed non-invasively using functional near infrared spectroscopy. Thanks to spectroscopy principles, it is possible to safety use a light beam in the infrared spectrum to infer the concentration of hemoglobin when bonded to oxygen. Its concentration is calculated in mM/L.

  1 hour after intervention

Secondary Outcomes (7)

• Pain

  1 hour after intervention

• Heat Pain Threshold

  1 hour after intervention

• Pressure Pain Threshold

  1 hour after intervention

• Maximal Heat Pain Tolerance

  1 hour after intervention

• Conditioned pain modulation

  1 hour after intervention

Study Arms (2)

Pregabalin

EXPERIMENTAL

Pregabalin 150 mg PO single dose

Drug: Pregabalin

Placebo

PLACEBO COMPARATOR

Placebo (a pill of same physical characteristics as the one used for the experimental arm, containing starch) PO single dose

Other: Placebo

Interventions

Pregabalin DRUG

Pregabalin 150 mg PO, single dose.

Pregabalin

Placebo OTHER

Pill of same physical characteristics as the one used for the intervention, containing starch only. Administered PO in single dose.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fulfill ACR 2010 criteria for fibromyalgia diagnosis.
• Literate.
• Mean VAS for pain higher than 6 in the last 3 months.

You may not qualify if:

• Pregnancy or inadequate use of validated contraceptive method.
• Contraindications for Transcranial Magnetic Stimulation.
• Alcohol of drugs abuse in the last 6 months.
• Any severe neurological, neurosurgical, cardiac, endocrinological, or oncological disease (current or past).
• Decompensated chronic systemic disease.
• Previous use of Pregabalin.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator
• Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.: collaborator
• Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil: collaborator

Related Publications (1)

• Deitos A, Soldatelli MD, Dussan-Sarria JA, Souza A, da Silva Torres IL, Fregni F, Caumo W. Novel Insights of Effects of Pregabalin on Neural Mechanisms of Intracortical Disinhibition in Physiopathology of Fibromyalgia: An Explanatory, Randomized, Double-Blind Crossover Study. Front Hum Neurosci. 2018 Nov 19;12:406. doi: 10.3389/fnhum.2018.00406. eCollection 2018.

  PMID: 30510505 DERIVED

MeSH Terms

Conditions

Fibromyalgia

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Wolnei Caumo, MD, PhD

  HCPA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: December 24, 2015
• Study Start: December 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: February 8, 2018

Record last verified: 2015-12