TMS + D-Cycloserine for Fibromyalgia

Overseen By Alexander McGirr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Benzodiazepines, Cyclopyrrolones, Anticonvulsants, others

Disqualifiers: Psychosis, Neurological disorders, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 4 weeks

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for fibromyalgia, a condition causing widespread pain, fatigue, and mood issues. Researchers combine a brain stimulation method called Transcranial Magnetic Stimulation (TMS) with a medication called D-Cycloserine to determine if it improves symptoms like pain and depression more effectively than TMS alone. Participants will receive either TMS with D-Cycloserine or TMS with a placebo. The trial seeks individuals diagnosed with fibromyalgia who haven't found relief from other treatments, such as certain medications or therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking fibromyalgia treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you have not changed your dose or started any new psychotropic medications in the 4 weeks before joining. Additionally, you cannot be taking benzodiazepines, cyclopyrrolones, gabapentin/pregabalin, anticonvulsants, ethionamide, or isoniazid.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Transcranial Magnetic Stimulation (TMS) is generally well-tolerated. This treatment uses magnetic fields to influence brain activity. It has been widely studied and is considered safe, especially when targeting brain areas linked to fibromyalgia symptoms.

Researchers have examined D-Cycloserine combined with intermittent theta-burst stimulation (iTBS) to enhance TMS effects. Although iTBS has not been specifically studied for fibromyalgia, it is known to be as safe as traditional TMS methods used for depression. This combination aims to alleviate symptoms like pain and mood issues by affecting brain function.

Overall, current research considers these treatments safe. However, like any treatment, they may have side effects. Participants should discuss any concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fibromyalgia?

Researchers are excited about the combination of iTBS (intermittent Theta Burst Stimulation) and D-Cycloserine for fibromyalgia because it introduces a novel approach to managing this chronic pain condition. Unlike traditional treatments such as pain relievers, antidepressants, or anti-seizure drugs, this treatment combines a form of non-invasive brain stimulation with a medication typically used as an antibiotic, repurposed here to potentially enhance the brain's plasticity. This unique pairing aims to target the brain’s pain processing pathways more directly and effectively, potentially offering quicker relief and improved pain management for patients who haven't found success with standard therapies.

What evidence suggests that this trial's treatments could be effective for fibromyalgia?

Research shows that transcranial magnetic stimulation (TMS) can significantly reduce pain in people with fibromyalgia, with studies indicating up to a 29% decrease in pain. TMS targets specific brain areas to improve mood and reduce anxiety, offering longer-lasting benefits when focusing on the dorsolateral prefrontal cortex (DLPFC). In this trial, some participants will receive TMS combined with a medication called D-Cycloserine (DCS), which might enhance these effects. Researchers believe DCS boosts the impact of TMS, especially when used with intermittent theta-burst stimulation (iTBS), which has shown promise in reducing symptoms of depression and anxiety. Although iTBS hasn't been directly studied for fibromyalgia, it has shown positive effects in similar conditions like depression. This combination could lead to better overall symptom relief for fibromyalgia patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Alexander McGirr, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

Adults aged 18-65 with fibromyalgia, who haven't responded to certain medications or therapy, can join this trial. They must score ≥41 on the FIQR, have normal recent blood work, and not be on new psychotropic meds for the last month. Pregnant individuals or those at significant risk of harm are excluded.

Inclusion Criteria

I have been diagnosed with fibromyalgia according to the 2016 criteria.

I haven't started or changed the dose of any mental health medication in the last 4 weeks.

Your recent blood tests must show normal levels of various substances like blood cells, electrolytes, and kidney and liver function markers.

Exclusion Criteria

I am experiencing symptoms of psychosis.

I do not have major brain or nerve conditions like severe head injury, epilepsy, or Parkinson's.

You have thoughts of hurting yourself or have answered a certain way on a depression screening test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 weeks of rTMS treatment with either D-Cycloserine or placebo, with daily capsule ingestion and 20 TMS sessions.

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of clinical symptoms, cognitive function, and imaging.

4 weeks

1 visit (in-person)

Extension

Optional continuation of monitoring and assessment to compare treatment effects with healthy controls.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• iTBS-DCS

Trial Overview The trial is testing if a brain stimulation technique called iTBS combined with D-Cycloserine (a medication) is more effective in treating fibromyalgia symptoms than iTBS alone. Participants will either receive D-Cycloserine or a placebo alongside TMS treatments.

How Is the Trial Designed?

Group I: D-Cycloserine Experimental Treatment 2 Interventions

Participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine daily (Monday-Friday) during 4 weeks of rTMS treatment (20 sessions) 60-120 minutes prior to rTMS treatment.

Group II: Placebo Placebo Group 2 Interventions

Participants will orally ingest a capsule identical to that containing the study medication, however this capsule will contain a placebo. They will ingest this capsule daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) 60 - 120 minutes prior to rTMS treatment.

iTBS-DCS is already approved in United States, Canada for the following indications:

Approved in United States as D-Cycloserine for:

• Urinary tract infections

Approved in Canada as D-Cycloserine for:

• Urinary tract infections

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

In a study of 38 fibromyalgia patients, those receiving high-frequency rTMS showed significant improvements in quality of life (QoL) after 10 weeks compared to those receiving sham stimulation, particularly in emotional and social aspects.

The improvement in QoL was linked to increased metabolism in the right medial temporal area of the brain, suggesting a neural basis for the emotional benefits of rTMS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic substrate. Boyer, L., Dousset, A., Roussel, P., et al.[2022]

Both intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced neuropathic pain in 33 patients with spinal cord injuries compared to sham treatment, demonstrating their efficacy.

iTBS may offer advantages over rTMS in terms of safety, convenience, and patient compliance, making it a potentially better option for treating neuropathic pain in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intermittent theta burst stimulation and high-frequency repetitive transcranial magnetic stimulation on spinal cord injury-related neuropathic pain: A sham-controlled study. Kim, JK., You, J., Son, S., et al.[2023]

In a study involving 46 patients with neuropathic pain, high-frequency repetitive transcranial magnetic stimulation (rTMS) was found to provide superior pain relief compared to intermittent theta-burst stimulation (iTBS) after 5 days of treatment.

The results indicated that 52% of patients responded positively to 20 Hz-rTMS, while only 32% responded to iTBS, and patients reported significantly less fatigue after rTMS, suggesting it may be a more effective option for managing neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison. André-Obadia, N., Magnin, M., Garcia-Larrea, L.[2021]

Intermittent theta burst stimulation (iTBS) significantly increases motor-evoked potentials (MEPs) and enhances the excitability of I-waves in the motor cortex, indicating its potential to improve motor function.

The study suggests that iTBS and continuous theta burst stimulation (cTBS) affect different neural circuits, which implies they may be used for targeting different therapeutic outcomes in conditions like pain management or motor rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. Di Lazzaro, V., Pilato, F., Dileone, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduces fibromyalgia symptoms, with a standardized mean difference of -0.700, indicating its efficacy in managing the disease's impact, especially in older patients.

The benefits of rTMS, including reductions in pain, depression, and anxiety, were observed to last for at least two weeks after treatment, and no serious adverse events were reported, highlighting its safety as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Su, YC., Guo, YH., Hsieh, PC., et al.[2021]

In a study of 30 female patients with fibromyalgia, both high-frequency rTMS protocols (targeting the primary motor cortex and dorsolateral prefrontal cortex) led to significant improvements in pain, quality of life, and depression compared to a sham treatment.

The group receiving rTMS targeting the primary motor cortex showed the greatest reduction in pain, while the dorsolateral prefrontal cortex group had more significant improvements in physical role functioning, highlighting the potential of rTMS as an effective intervention for fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is high-frequency repetitive transcranial magnetic stimulation of the left primary motor cortex superior to the stimulation of the left dorsolateral prefrontal cortex in fibromyalgia syndrome? Altas, EU., Askin, A., Beşiroğlu, L., et al.[2020]

In a study of 40 patients with fibromyalgia, active repetitive transcranial magnetic stimulation (rTMS) significantly reduced pain intensity from day 5 to week 25, demonstrating long-term analgesic effects.

The pain relief from rTMS was associated with improvements in quality of life, including reduced fatigue and better sleep, and correlated with changes in brain activity related to pain processing, suggesting rTMS is a promising and safe treatment option for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. Mhalla, A., Baudic, S., de Andrade, DC., et al.[2022]

A systematic review of 7 high-quality randomized controlled trials involving 217 patients found that 10-Hz repetitive transcranial magnetic stimulation (rTMS) significantly reduced pain and improved quality of life in individuals with fibromyalgia compared to sham stimulation.

While 10-Hz rTMS effectively alleviated pain (SMD=-0.72) and enhanced quality of life (SMD=-0.70), it did not show a significant impact on depression levels (SMD=-0.23), indicating its primary benefit lies in pain management rather than mood improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis. Zhu, PA., Xie, JY., Liu, H., et al.[2023]

In a study involving 20 patients with fibromyalgia, those receiving active transcranial magnetic stimulation (TMS) experienced a significant 29% reduction in pain symptoms compared to their baseline, while the sham group showed only a 4% change.

Active TMS also led to significant improvements in depression symptoms after treatment, indicating that pain reduction occurred before any antidepressant effects, and the treatment was well tolerated with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: a randomized, controlled pilot study. Short, BE., Borckardt, JJ., Anderson, BS., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been shown to significantly reduce pain in fibromyalgia patients, with 80% of rTMS studies and 100% of tDCS studies reporting positive outcomes.

Excitatory rTMS/tDCS targeting the primary motor cortex (M1) not only provided effective pain relief but also had fewer side effects compared to traditional fibromyalgia medications, making it a promising alternative for patients seeking relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Marlow, NM., Bonilha, HS., Short, EB.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05395494

Study Details | NCT05395494 | iTBS-DCS in Fibromyalgia Specifically, this data indicated that several converging features of fibromyalgia improve with augmented iTBS, specifically depressive symptoms, anxiety ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05395494/itbs-dcs-in-fibromyalgia

iTBS-DCS in Fibromyalgia | Clinical Research Trial Listing Background & Rationale: Fibromyalgia is characterized by widespread pain, fatigue, mood and anxiety as well as cognitive complaints.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9557938/

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta- ... This randomized clinical trial investigates the efficacy of transcranial magnetic stimulation enhanced with adjunctive D-cycloserine to manage major depressive ...

4. withpower.com withpower.com/trial/phase-2-fibromyalgia-5-2022-ac87e

TMS + D-Cycloserine for Fibromyalgia · Info for Participants Research shows that transcranial magnetic stimulation (TMS) can reduce pain in fibromyalgia patients, with one study finding a 29% reduction in pain after TMS ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36223114/

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta- ... Findings from this clinical trial indicate that adjunctive D-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment ...

6. ctv.veeva.com ctv.veeva.com/study/the-effect-of-intermittent-theta-burst-stimulation-on-pain-intensity-pain-catastrophizing-quality

Intermittent Theta Burst Stimulation in Fibromyalgia Syndrome This study has a prospective, parallel group, randomized, sham-controlled study design. A total of 30 fibromyalgia patients will be randomized ...