TMS + D-Cycloserine for Fibromyalgia

Overseen by Alexander McGirr, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Calgary

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

Disqualifiers: Psychosis, Neurological disorders, Pregnancy, others

Stay on Your Current Meds

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for fibromyalgia using magnetic brain stimulation combined with a medication. It aims to help adults with fibromyalgia who haven't found relief from other treatments. The treatment works by using magnets to change brain activity and the medication to boost this effect.

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.

What data supports the effectiveness of the treatment iTBS-DCS for fibromyalgia?

Research shows that transcranial magnetic stimulation (TMS) can reduce pain in fibromyalgia patients, with one study finding a 29% reduction in pain after TMS sessions. Additionally, intermittent theta-burst stimulation (iTBS), a form of TMS, has been effective in reducing neuropathic pain, suggesting potential benefits for fibromyalgia as well. ^{1 2 3 4 5}

Is the combination of TMS and D-Cycloserine safe for humans?

Research on repetitive transcranial magnetic stimulation (rTMS) for fibromyalgia shows it is generally safe, with no serious side effects reported. However, specific safety data for the combination of TMS and D-Cycloserine is not available in the provided studies. ^{3 6 7 8 9}

How is the iTBS-DCS treatment different from other fibromyalgia treatments?

The iTBS-DCS treatment combines intermittent theta-burst stimulation (a type of brain stimulation) with D-Cycloserine (a medication that can enhance brain plasticity), offering a novel approach that may improve pain and quality of life in fibromyalgia patients by potentially enhancing the effects of brain stimulation. ^{3 5 7 8 10}

Research Team

Alexander McGirr, MD

Principal Investigator

University of Calgary

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• iTBS-DCS (Other)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Shweta Patel

University of Calgary

Chief Medical Officer since 2020

MD from the University of Baroda Medical College, India

Dr. Edward McCauley

University of Calgary

President and Vice-Chancellor since 2018

PhD in Ecology and Evolutionary Biology from the University of California, Santa Barbara

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. [2022]

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

Ten sessions of adjunctive left prefrontal rTMS significantly reduces fibromyalgia pain: a randomized, controlled pilot study. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison. [2021]

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

rTMS in fibromyalgia: a randomized trial evaluating QoL and its brain metabolic substrate. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Repetitive Transcranial Magnetic Stimulation in Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2021]

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

Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. [2022]

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

Long-term maintenance of the analgesic effects of transcranial magnetic stimulation in fibromyalgia. [2022]

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

Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation at 10 Hz in Fibromyalgia: A Systematic Review and Meta-analysis. [2023]

10. England 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? [2020]