FibromyalgiaPhase 2/3NCT02639533
Brain Response to Single Dose of Pregabalin in Fibromyalgia
A Phase 2/3 study testing Pregabalin in people with Fibromyalgia, run by Hospital de Clinicas de Porto Alegre.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Pregabalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- No sites listed yet
- Study dates
- Dec 2014to Jan 2017
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Fulfill ACR 2010 criteria for fibromyalgia diagnosis.
- Literate.
- Mean VAS for pain higher than 6 in the last 3 months.
Who cannot join
- 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.
About this study
Official title: Pregabalin Acute Effects on Cortical Excitability, Psychophysical Parameters, and Serum Markers of Neuroplastic Processes in Fibromyalgia: a Placebo Controlled, Double Blinded, Randomized, Crossover Clinical Trial
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.
Read the detailed description
A crossover, double-blinded randomized clinical trial is proposed. The investigators will recruit literate adult females aging 18 to 65 years old; fulfilling the diagnosis criteria for fibromyalgia according to the American College of Rheumatology 2010; with mean pain ≥6 in the verbal analog scale; who speak Brazilian Portuguese; and were able to perform the three visits. Female adult participants without chronic pain will also be recruited. Participants with severe psychiatric disorders that would limit consenting; neurologic deficits; decompensated systemic disease or chronic inflammatory disorders (Systemic Erythematous Lupus or Rheumatoid arthritis); contraindications for TMS; and those with previous use of Pregabalin will be excluded.
In the investigators' study, participants 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.
In the first visit, after explaining the research, solving doubts and signing the informed consent, participants will be randomized to an allocation sequence (either Pregabalin in the second or in the third visit). Then, a blood sample will be gathered and participants will be asked to fill some questionnaires to understand better their pain, and its impact on their quality of life (Fibromyalgia Impact Questionnaire), Anxiety (State/Trait Anxiety Inventory), Depressive symptoms (Beck Depression Inventory II), Catastrophizing thinking (Pain Catastrophizing Scale - PCS), Sleep (Pittsburgh Sleep Quality Index), and resiliency. Then, a fingertapping task will be performed while assessing hemodynamic changes using fNIRS. After that, heat perception will be tested using quantitative sensory testing (QST) and Conditioned Pain Modulation (CPM) with cold. Also, the pain pressure threshold (PPT) using a digital algometer will be evaluated. Finally, cortical excitability parameters (motor evoked potentials, intracortical facilitation and inhibition, and cortical silent period) will be determined using paired pulsed TMS.
In the second visit, according to the randomized allocation participants will receive either Pregabalin 150 mg PO or Placebo. Then, the M.I.N.I. International Neuropsychiatric Interview will be performed. One hour after taking the medication, the fNIRS, QST, CPM, PPT and TMS evaluations will be repeated, and a new blood sample will be collected. In the third visit, a blood sample will be gathered, followed by administration of the corresponding intervention according to the randomized allocation. Then, the pain level, PCS, STAI and International Physical Activity Questionnaire (IPAQ) will be asked again. One hour after taking the medication, the fNIRS, QST, CPM, PPT and TMS evaluations will be repeated, and a final blood sample will be collected. Participants' guess about blinding will be assessed after each intervention. All evaluators will remain blind to the allocation.
- Conditions
- Fibromyalgia
- Being tested
- Pregabalin, Placebo
- Keywords
- fibromyalgia, pregabalin, cortical excitability, functional near infrared spectroscopy
- Medical subject headings
- Fibromyalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregabalinDrug
Pregabalin 150 mg PO, single dose.
PlaceboOther
Pill of same physical characteristics as the one used for the intervention, containing starch only. Administered PO in single dose.
| Study group | Role | What they receive |
|---|---|---|
| Pregabalin | Experimental | Pregabalin 150 mg PO single dose Receives: 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 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 1 hour after intervention
Secondary outcomes (7)
Pain
Assessed with the Visual Analog Scale
Measured: 1 hour after intervention
Heat Pain Threshold
Assessed using quantitative sensory testing. Briefly, a thermode placed in subjects forearm is heated controlled by a computer. Subjects are instructed to report when perceiving the first pain. Temperatures in Celcius degrees are recorded.
Measured: 1 hour after intervention
Pressure Pain Threshold
Assessed using a digital algometer. Briefly, progressive pressure is applied in subjects forearm until the first perception of pain is reported. The pressure of the first perception of pain are recorded in Kg/cm^2 .
Measured: 1 hour after intervention
Maximal Heat Pain Tolerance
Assessed using quantitative sensory testing. Briefly, the thermode placed in subjects forearm is heated until subject reports maximum tolerated pain. A maximal temperature of 52 Celcius has been previously programmed for the device to stop and cool down in order to avoid unintended injuries.
Measured: 1 hour after intervention
Conditioned pain modulation
The protocol for heat pain threshold is repeated while the contralateral hand is placed on iced water. The pain due to heat and cold reported on a Visual Analog Scale are recorded.
Measured: 1 hour after intervention
Serum Brain Derived Neurotrophic Factor (BDNF)
Blood samples will be gathered at baseline and 2 hours after receiving the intervention to quantify the serum BDNF concentration (ng/mL).
Measured: Baseline and 2 hours after intervention
Serum Protein S100B
Blood samples will be gathered at baseline and 2 hours after receiving the intervention to quantify the serum S100B concentration (pg/mL).
Measured: Baseline and 2 hours after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2015 (estimated)
- Study startDec 2014
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- More trials run by Hospital de Clinicas de Porto AlegreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil
- Responsible party
- Sponsor
- Investigators
- Wolnei Caumo, MD, PhD, Principal investigator, HCPA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02639533
- Sponsor's protocol ID
- 14-0624
- Status last verified
- Dec 2015
- First submitted
- 11 Nov 2015
- Last updated
- 8 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 30510505
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pregabalin Acute Effects on Cortical Excitability, Psychophysical Parameters, and Serum Markers of Neuroplastic Processes in Fibromyalgia: a Placebo Controlled, Double Blinded, Randomized, Crossover Clinical Trial
- ClinicalTrials.gov ID
- NCT02639533
- Acronym / sponsor ID
- 14-0624
- Conditions
- Fibromyalgia
- Keywords
- fibromyalgia, pregabalin, cortical excitability, functional near infrared spectroscopy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior., Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil
- Study start
- Dec 2014
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 24 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A crossover, double-blinded randomized clinical trial is proposed. The investigators will recruit literate adult females aging 18 to 65 years old; fulfilling the diagnosis criteria for fibromyalgia according to the American College of Rheumatology 2010; with mean pain ≥6 in the verbal analog scale; who speak Brazilian Portuguese; and were able to perform the three visits. Female adult participants without chronic pain will also be recruited. Participants with severe psychiatric disorders that would limit consenting; neurologic deficits; decompensated systemic disease or chronic inflammatory disorders (Systemic Erythematous Lupus or Rheumatoid arthritis); contraindications for TMS; and those with previous use of Pregabalin will be excluded.
In the investigators' study, participants 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.
In the first visit, after explaining the research, solving doubts and signing the informed consent, participants will be randomized to an allocation sequence (either Pregabalin in the second or in the third visit). Then, a blood sample will be gathered and participants will be asked to fill some questionnaires to understand better their pain, and its impact on their quality of life (Fibromyalgia Impact Questionnaire), Anxiety (State/Trait Anxiety Inventory), Depressive symptoms (Beck Depression Inventory II), Catastrophizing thinking (Pain Catastrophizing Scale - PCS), Sleep (Pittsburgh Sleep Quality Index), and resiliency. Then, a fingertapping task will be performed while assessing hemodynamic changes using fNIRS. After that, heat perception will be tested using quantitative sensory testing (QST) and Conditioned Pain Modulation (CPM) with cold. Also, the pain pressure threshold (PPT) using a digital algometer will be evaluated. Finally, cortical excitability parameters (motor evoked potentials, intracortical facilitation and inhibition, and cortical silent period) will be determined using paired pulsed TMS.
In the second visit, according to the randomized allocation participants will receive either Pregabalin 150 mg PO or Placebo. Then, the M.I.N.I. International Neuropsychiatric Interview will be performed. One hour after taking the medication, the fNIRS, QST, CPM, PPT and TMS evaluations will be repeated, and a new blood sample will be collected. In the third visit, a blood sample will be gathered, followed by administration of the corresponding intervention according to the randomized allocation. Then, the pain level, PCS, STAI and International Physical Activity Questionnaire (IPAQ) will be asked again. One hour after taking the medication, the fNIRS, QST, CPM, PPT and TMS evaluations will be repeated, and a final blood sample will be collected. Participants' guess about blinding will be assessed after each intervention. All evaluators will remain blind to the allocation.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregabalin | Experimental | Drug: PregabalinPregabalin 150 mg PO single dose |
| Placebo | Placebo comparator | Other: PlaceboPlacebo (a pill of same physical characteristics as the one used for the experimental arm, containing starch) PO single dose |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Fulfill ACR 2010 criteria for fibromyalgia diagnosis.
- Literate.
- Mean VAS for pain higher than 6 in the last 3 months.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PregabalinPregabalin 150 mg PO, single dose. | Drug | Pregabalin |
| PlaceboPill of same physical characteristics as the one used for the intervention, containing starch only. Administered PO in single dose. | Other | Placebo |
Primary outcome
Cortical Excitability: Intracortical Inhibition.
Time frame: 1 hour after intervention
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.
Cortical hemodynamics: Oxy-hemoglobin concentration (mM/L)
Time frame: 1 hour after intervention
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.
7 secondary outcomes
Pain
Time frame: 1 hour after intervention
Heat Pain Threshold
Time frame: 1 hour after intervention
Pressure Pain Threshold
Time frame: 1 hour after intervention
Maximal Heat Pain Tolerance
Time frame: 1 hour after intervention
Conditioned pain modulation
Time frame: 1 hour after intervention
Serum Brain Derived Neurotrophic Factor (BDNF)
Time frame: Baseline and 2 hours after intervention
Serum Protein S100B
Time frame: Baseline and 2 hours after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2018.
- Derived from this study: PubMed 30510505Deitos 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wolnei Caumo, MD, PhD principal investigator
HCPA
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pregabalin in people with Fibromyalgia, run by Hospital de Clinicas de Porto Alegre.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortical Excitability: Intracortical Inhibition. (time frame: 1 hour after intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02639533, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2018.