Brain Imaging Study for Fibromyalgia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Nova Scotia Health Authority
Disqualifiers: Cardiac, Respiratory, Nervous system, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Drugs used for managing Fibromyalgia pain have not proven to be effective and pain continues to cost Canadians $60 billion a year without truly helping those who suffer. The study proposes to investigate the factors related to a person that can enhance or reduce the effectiveness of pain treatments in people suffering with Fibromyalgia pain. Treatment response to painkillers in a person may be related to their brain, social, and psychological makeup. The investigators aim to study these factors to identify and develop feasible and robust indicators based on a person's biological makeup (also called biomarkers). These biomarkers will allow doctors and researchers to predict more accurately which treatment and prevention strategies for a particular disease will work in which groups of people. These measures will offer new opportunities for improving treatment such as by tailoring treatment to meet the specific needs of each patient based on his/her biological and psychological makeup. Towards the specific aim, data will first be collected in several experimental domains for studying treatment expectations (cognitive, psychosocial, brain-related). These 'experimental' data will be compared between Fibromyalgia (FM) and healthy participants to yield new understanding of the factors that govern treatment response. At the end of experimental data collection, the investigators will collect data in the 'clinical' domain. Hence, at the end of the experimental sessions, a subset of FM participants will receive a mock drug (placebo disguised as an approved pain treatment) and another subset will provide pain ratings only and hence serve as a waiting list control for the placebo trial. Data will be studied in steps to understand factors that mediate treatment outcomes and finally the investigators will use advanced computational tools used for big data analysis and aim to identify factors that can be used as biomarkers and precision medicine tools.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team for clarification.
What data supports the effectiveness of placebo treatment for fibromyalgia?
Research shows that placebo treatments can lead to moderate improvements in pain, fatigue, sleep quality, and physical function in fibromyalgia patients. The effectiveness of placebo treatments is influenced by factors like the strength of the active treatment, age, and baseline pain severity.
12345Is the treatment in the fibromyalgia brain imaging study safe for humans?
The research indicates that in trials for fibromyalgia, both the actual drugs and placebos can cause side effects, leading to some participants dropping out. This suggests that while the treatment may be generally safe, there are still some risks of adverse effects.
12346How does this treatment for fibromyalgia differ from other treatments?
This treatment is unique because it involves brain imaging to study fibromyalgia, focusing on brainstem dysfunction and altered dopamine metabolism, which are not typically addressed by standard fibromyalgia treatments. This approach may provide insights into the brain's role in fibromyalgia, potentially leading to novel therapeutic strategies.
14789Eligibility Criteria
This trial is for adults aged 18-75 with Fibromyalgia or chronic low back pain, experiencing at least moderate pain. Participants must be right-handed and comfortable with English tasks. It excludes those with certain diseases like asthma, claustrophobia, or conditions that conflict with MRI scanning such as having a pacemaker or being pregnant.Inclusion Criteria
You are right-handed.
You are right-handed and experience chronic pain.
You are right-handed.
+11 more
Exclusion Criteria
Healthy participant: Presence of any contraindications to MRI scanning. For example: cardiac pacemaker, metal implants, fear of closed spaces, pregnancy
You have any health issues that prevent you from having an MRI scan, like a pacemaker, metal implants, fear of small spaces, or being pregnant.
Healthy participant: History of cardiac, respiratory, or nervous system disease that, in the investigator's judgment and by asking the participant about their comfort level and ability, precludes participation in the study because of a heightened potential for adverse outcome. For example: asthma or claustrophobia
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Experimental Data Collection
Data collected in cognitive, psychosocial, and brain-related domains to study treatment expectations
Varies
Clinical Data Collection
A subset of FM participants receive a placebo and another subset provides pain ratings as a control
3 days
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests how different factors like brain activity and psychological state influence the effectiveness of pain treatments in Fibromyalgia patients. Some participants will receive a placebo disguised as real medication to assess treatment expectations and response.
3Treatment groups
Experimental Treatment
Active Control
Group I: Experimental: placebosExperimental Treatment1 Intervention
Fibromyalgia participants will enter in an optional placebo trial. This phase of the study will test the clinical usefulness of the biomarkers. We will measure how expectation of starting a new treatment reduces 'clinical back pain' in each participant. Positive treatment expectations will be induced by giving them capsules containing inert material and telling them that the capsules contain an effective drug that has been approved for treating Chronic Back Pain. They will be requested to take two capsules four times a day and report their pain on paper forms organized as a calendar or on REDCap.
Group II: WaitlistActive Control1 Intervention
Fibromyalgia participants will not be given any placebo and will be requested to report their pain on paper forms organized as a calendar or on REDCap.
Group III: Healthy ControlsActive Control1 Intervention
Healthy control participants will complete the main part of the study, but will not be asked to take a placebo or be placed on a waitlist.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nova Scotia Health AuthorityHalifax, Canada
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Who Is Running the Clinical Trial?
Nova Scotia Health AuthorityLead Sponsor
References
Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain. [2022]Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results.
The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials. [2018]The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition.
Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. [2022]The superiority of true drug treatment over placebo in reducing symptoms of fibromyalgia syndrome (FMS) is small and bought by relevant rates of drop-outs due to adverse events. Recent systematic reviews demonstrated that a substantial proportion of the beneficial and adverse effects of true drug is attributable to placebo in chronic pain trials. We determined the magnitude of the placebo and nocebo response and its impact on the benefits and harms of true drug in trials of drugs which were submitted for approval for treatment of FMS.
Fibromyalgia: can one distinguish it from simulation? An observer-blind controlled study. [2004]A randomized controlled trial was conducted to assess reliability and accuracy in identification of fibromyalgia (FM), motivated simulation, and normal controls.
Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals. [2023]Placebo analgesia is hypothesized to involve top-down engagement of prefrontal regions that access endogenous pain inhibiting opioid pathways. Fibromyalgia (FM) patients have neuroanatomical and neurochemical alterations in pathways relevant to placebo analgesia. Thus, it remains unclear whether placebo analgesic mechanisms would differ in FM patients compared to healthy controls (HCs). Here, using placebo-analgesia-inducing paradigms that included verbal suggestions and conditioning manipulations, we examined whether behavioral and neural placebo analgesic responses differed between 32 FM patients and 46 age- and sex-matched HCs. Participants underwent a manipulation scan, where noxious high and low heat were paired with the control and placebo cream, respectively, and a placebo experimental scan with equal noxious heat temperatures. Before the experimental scan, each participant received saline or naloxone, an opioid receptor antagonist. Across all participants, the placebo condition decreased pain intensity and unpleasantness ratings, decreased activity within the right insula and bilateral secondary somatosensory cortex, and modulated the neurologic pain signature. There were no differences between HCs and FM patients in pain intensity ratings or neural responses during the placebo condition. Despite the perceptual and neural effects of the placebo manipulation, prefrontal circuitry was not activated during the expectation period and the placebo analgesia was unaltered by naloxone, suggesting placebo effects were driven more by conditioning than expectation. Together, these findings suggest that placebo analgesia can occur in both HCs and chronic pain FM patients, without the involvement of opioidergic prefrontal modulatory networks.
Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome. [2019]To compare the validity of self-reported questionnaires as response criteria of treatment efficacy in patients with fibromyalgia syndrome.
Motor cortical dysfunction disclosed by single and double magnetic stimulation in patients with fibromyalgia. [2022]To investigate the motor cortex by single and double magnetic stimulation, in patients with fibromyalgia.
Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism. [2016]Fibromyalgia (FM) has been associated with alterations in brain morphometry and abnormal dopaminergic neurotransmission. Evidence from preclinical models has demonstrated that dopamine plays a role in promoting neuronal integrity. We therefore sought to confirm previous findings of reduced gray matter density in subjects with FM and to determine whether variations in dopamine metabolism might affect gray matter density. Voxel-based morphometry was used to evaluate anatomical magnetic resonance imaging data from 30 female FM subjects in comparison with 20 age- and gender-matched healthy control subjects. In addition, data from a subset of subjects from both groups who had previously participated in our positron emission tomography study using radiolabeled DOPA (n = 14; 6 FM subjects and 8 control subjects) was used to determine whether correlation might exist between gray matter density and dopamine metabolism. We found a significant reduction in gray matter density within the bilateral parahippocampal gyri, right posterior cingulate cortex, and left anterior cingulate cortex. In addition, a positive correlation was demonstrated between an index of dopamine metabolism from the ventral tegmental area wherein cell bodies of corticolimbic projection neurons originate and gray matter density, specifically in the bilateral parahippocampal gyri and left pregenual cortex. The current results confirm our previous findings that FM is associated with altered brain morphometry. Alterations in dopamine metabolism might contribute to the associated changes in gray matter density.
Alterations in excitatory and inhibitory brainstem interneuronal circuits in fibromyalgia: evidence of brainstem dysfunction. [2018]Patients with fibromyalgia syndrome (FMS) perceive stimuli differently and show altered cortical sensory representation maps following peripheral stimulation. Altered sensory gating may play a causal role.