NCT05395494

iTBS-DCS in Fibromyalgia

A Randomized Controlled Trial of Adjunctive D-Cycloserine to Intermittent Theta-burst Stimulation Transcranial Magnetic Stimulation in Fibromyalgia

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (actual)
• Sponsor: University of Calgary · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

Background \& Rationale: Fibromyalgia is characterized by widespread pain, fatigue, mood and anxiety as well as cognitive complaints. For an unacceptable proportion of patients, depressive symptoms remain impairing despite multiple treatments. For such patients, novel treatments include non-invasive brain stimulation. Transcranial Magnetic Stimulation (TMS) targeting the dorsolateral prefrontal cortex (DLPFC) or the primary motor cortex (M1) is the non-invasive neurostimulation method with the largest evidence base in fibromyalgia. It involves generating magnetic fields outside of the body to change the firing of neurons in the brain, and has a very favorable tolerability profile. Recent meta-analyses indicate that both the DLPFC and M1 targets are associated with improvements in pain, mood and anxiety, however the benefits are more persistent when the DLPFC is targeted (Su et al, 2021 - J Clin Med). The DLPFC is important in fibromyalgia through its implication in several symptoms domains in fibromyalgia, as well as pain catastrophization. The researchers neurophysiological data and clinical data in depression suggests that the researchers can enhance the effects of TMS by using an adjunctive medication called D-Cycloserine (DCS, 100mg) in conjunction with a protocol called intermittent theta-burst stimulation (iTBS). Specifically, this data indicated that several converging features of fibromyalgia improve with augmented iTBS, specifically depressive symptoms, anxiety symptoms, fatigue, and cognitive function. The researchers therefore hypothesize that the combination of D-cycloserine and TMS will lead to greater improvements in fibromyalgia symptoms than TMS alone. Although iTBS has not yet been studied in fibromyalgia, it has a well characterized neurophysiological effect and been shown to be non-inferior to conventional TMS protocols in conditions such as depression. More importantly, its physiological basis can be manipulated with D-Cycloserine whereas this has not been convincingly demonstrated with rTMS (see Brown et al, 2019, 2021 Brain Stim). Research Question and Objectives: To conduct a randomized placebo-controlled trial of DCS in adjunct with rTMS in Fibromyalgia. Participants will be randomized to receive 100mg of DCS or placebo together with TMS.

Detailed description

Methods: 90participants (males and females aged aged 18-65, with a diagnosis of fibromyalgia of at least moderate moderate impact as defined by a FIQR score of ≥39, stable psychotropic medication for 4 weeks) will be recruited. Patients will be randomized 1:1 to TMS+DCS or TMS+Placebo. Participants who do not have recent bloodwork will have laboratory tests to rule out haematological, hepatic, and renal disease, and participants will be screened for suicidal ideation. The dose of DCS will be 100mg, taken daily for four weeks. Clinical outcomes will be quantified using the Revised Fibromyalgia Impact Questionnaire (FIQR), as well as clinical and self reported measures of depression, anxiety, and quality of life done at baseline, halfway through TMS treatment (week 2), and after TMS treatment (week 4). Participants clinical symptoms will be evaluated again one-month after treatment (week 8). Quantitative sensory testing done at baseline and week 4 will characterize sensory perception. Blood samples at baseline and week 4 will be used to analyze changes in pro-inflammatory markers. Changes in cognition will be assessed by cognitive testing at baseline, week 4, and week 8. MRI scans completed at baseline and week 4. MRI scans at baseline and week 4 will be used to assess the following neuroimaging outcomes: single voxel magnetic resonance spectroscopy, locus coeruleus neuromelanin, and functional MRI resting state connectivity. In parallel, a matched sample of 90 healthy participants will be cross-sectionally characterized for normative comparison, and these participants will not go on to receive any TMS or other interventions. Having this sample of healthy participants will allow the researchers to determine the clinical, cognitive, sensory, and imaging characteristics that characterize fibromyalgia. They will also allow the researchers to determine whether treatment effects restore clinical, cognitive, sensory, and imaging characteristics to the level of healthy controls.

Conditions

• Fibromyalgia

Interventions

Type	Name	Description
DRUG	D-Cycloserine	Daily oral D-cycloserine 100mg during TMS treatments (20 days). Other Names: Seromycin
DRUG	Placebo oral tablet	Daily oral placebo during the TMS treatments (20 days).
DEVICE	iTBS repetitive Transcranial Magnetic Stimulation (rTMS)	Repetitive Transcranial magnetic stimulation (rTMS) will be delivered using a MagPro X100 device with B70 coil and the intermittent theta burst (iTBS) protocol to the left dorsolateral prefrontal cortex. Participants will receive daily treatments (Monday-Friday) over four weeks.

Timeline

• Start date: 2022-08-29
• Primary completion: 2025-07-31
• Completion: 2025-07-31
• First posted: 2022-05-27
• Last updated: 2025-08-17

Locations

1 site across 1 country: Canada

Regulatory

• FDA-regulated drug study
• FDA-regulated device study