Brain Imaging Study for Fibromyalgia

Overseen By Javeria A Hashmi, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nova Scotia Health Authority

Disqualifiers: Cardiac, Respiratory, Nervous system, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 2 3 4 6}

How 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. ^{1 4 7 8 9}

Eligibility 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.

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

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

Treatment Details

Interventions

• Placebos

Trial Overview 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.

Participant Groups

Group I: Experimental: placebos Experimental Treatment 1 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: Waitlist Active Control 1 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 Controls Active Control 1 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.

Who Is Running the Clinical Trial?

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Findings from Research

In a study of 37 fibromyalgia patients, longer duration of fibromyalgia pain was linked to reduced effectiveness of placebo analgesia, indicating that chronic pain may impair the body's natural pain relief mechanisms.

The findings suggest that early intervention in fibromyalgia is crucial, as patients with shorter pain duration may still benefit from endogenous pain regulation, highlighting the need to consider pain duration in placebo-controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain. Kosek, E., Rosen, A., Carville, S., et al.[2022]

Placebo treatment in randomized controlled trials for fibromyalgia significantly improved pain, fatigue, sleep quality, and physical function compared to no treatment, with a moderate effect size of 0.53.

The magnitude of the placebo effect was influenced by factors such as the strength of the active treatment, participant age, and baseline pain severity, while it decreased in studies with a higher proportion of women and longer disease duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials. Chen, X., Zou, K., Abdullah, N., et al.[2018]

In a review of 18 studies involving 3546 patients with fibromyalgia syndrome, a significant 18.6% of participants experienced a 50% reduction in pain from placebo treatments, highlighting the strong placebo effect in chronic pain trials.

The study also found that 10.9% of patients in placebo groups dropped out due to adverse events, indicating a notable nocebo effect, which suggests that both placebo and nocebo responses play a critical role in the perceived efficacy and safety of drug treatments for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. Häuser, W., Sarzi-Puttini, P., Tölle, TR., et al.[2022]

In a randomized controlled trial involving 27 female participants (8 with fibromyalgia and 19 healthy volunteers), examiners achieved an 80% accuracy rate in distinguishing between fibromyalgia patients, normal controls, and those simulating the condition.

Despite the high accuracy, the study revealed that about one-third of simulators were misidentified as having fibromyalgia, and one-fifth of fibromyalgia patients were misidentified as simulators, indicating challenges in accurately diagnosing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibromyalgia: can one distinguish it from simulation? An observer-blind controlled study. Khostanteen, I., Tunks, ER., Goldsmith, CH., et al.[2004]

Both fibromyalgia patients and healthy controls experienced similar levels of placebo analgesia, indicating that the mechanisms of pain relief through placebo are effective in chronic pain conditions as well.

The study found that the placebo effect was not influenced by opioid pathways, as naloxone (an opioid antagonist) did not alter the analgesic response, suggesting that conditioning rather than expectation plays a key role in placebo analgesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals. Frangos, E., Čeko, M., Wang, B., et al.[2023]

In a study of 70 fibromyalgia patients, the Regional Pain Score (RPS) was found to have a strong correlation with clinical assessments of treatment efficacy, indicating it is a valid tool for evaluating pain and treatment impact.

The RPS also demonstrated good discriminative power, with 75% sensitivity and 74% specificity in identifying effective treatments, making it a reliable measure for assessing treatment outcomes in fibromyalgia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome. Finckh, A., Morabia, A., Deluze, C., et al.[2019]

The study found that patients with fibromyalgia exhibited enhanced cortical relaxed thresholds and reduced cortical silent periods, indicating motor cortical dysfunction that affects both excitatory and inhibitory mechanisms.

The absence of facilitatory responses and reduced inhibitory responses in fibromyalgia patients suggest that their motor cortex is involved in chronic pain mechanisms, similar to those seen in rheumatoid arthritis, indicating a potential commonality in central pain processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor cortical dysfunction disclosed by single and double magnetic stimulation in patients with fibromyalgia. Salerno, A., Thomas, E., Olive, P., et al.[2022]

Fibromyalgia (FM) is linked to significant reductions in gray matter density in specific brain regions, such as the parahippocampal gyri and anterior cingulate cortex, which are related to pain perception and cognitive function.

There is a positive correlation between dopamine metabolism and gray matter density in FM patients, suggesting that alterations in dopamine may contribute to the brain changes observed in this disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism. Wood, PB., Glabus, MF., Simpson, R., et al.[2016]

In a study involving 10 female patients with fibromyalgia syndrome (FMS) and 26 healthy controls, the blink reflex was found to be normal in patients, indicating that basic reflex responses are intact despite their condition.

However, patients with FMS showed enhanced blink reflex excitability recovery and reduced prepulse inhibition, suggesting that there are functional changes in brainstem processing related to sensory gating, which may contribute to their altered perception of stimuli.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in excitatory and inhibitory brainstem interneuronal circuits in fibromyalgia: evidence of brainstem dysfunction. Kofler, M., Halder, W.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomised controlled trials. [2018]

3. Italy pubmed.ncbi.nlm.nih.gov

Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

Fibromyalgia: can one distinguish it from simulation? An observer-blind controlled study. [2004]

5. United States pubmed.ncbi.nlm.nih.gov

Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Validation of questionnaire-based response criteria of treatment efficacy in the fibromyalgia syndrome. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Motor cortical dysfunction disclosed by single and double magnetic stimulation in patients with fibromyalgia. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism. [2016]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Alterations in excitatory and inhibitory brainstem interneuronal circuits in fibromyalgia: evidence of brainstem dysfunction. [2018]