iTBS-DCS in Fibromyalgia

• Status: Not yet recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

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.

Our neurophysiological data and clinical data in depression suggests that we can enhance the effects of TMS by using an adjunctive medication called D-Cyloserine (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. We 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Calgary
• Treatments: Cycloserine

Criteria

Inclusion Criteria:

1. Males and females aged 18 to 65 years

2. are competent to consent to treatment

3. have a diagnosis of fibromyalgia as per the American College of Rheumatology 2016 fibromyalgia criteria.

4. have failed to achieve a clinical response to an adequate trial of a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, cognitive behavioral therapy or have been unable to tolerate these medications/access psychotherapy.

5. have a score ≥ 41 on the FIQR.

6. have had no change in dose, or initiation of any psychotropic medication in the 4 weeks prior to randomization

7. are able to adhere to the treatment schedule

8. pass the TMS adult safety screening (TASS) and MRI screening questionnaire

9. have had blood work within the last month (complete blood count, electrolytes, BUN, creatinine, eGFR, AST, ALT and GGT) within the reference range.

Exclusion Criteria:

1. Allergy to cycloserine or any excipients.

2. have an alcohol or substance use disorder within the last 3 months

3. have suicidal ideation (score of 4 ≥ on item 10 of MADRS or positive response to item 4 on the CSSRS-screen)

4. are at a significant risk of harm to themselves or others

5. current symptoms of psychosis

6. history of psychosis

7. are currently pregnant, breast feeding or plan to become pregnant. Health Canada requires that women of reproductive potential utilize either highly effective birth control or double barrier method of contraception. Abstinence is only acceptable when it is the usual and preferred lifestyle of the participant.

8. history of non-response to rTMS treatment.

9. have any significant neurological disorder or insult including, but not limited to:

any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes

10. have concomitant major unstable medical illness, cardiac pacemaker, or implanted medication pump

11. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed

12. If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study

13. are currently (or in the last 4 weeks) not taking any benzodiazepine, cyclopyrrolone, gabapentin/pregabalin or anticonvulsant due to the potential to limit iTBS efficacy

14. are being currently treated with ethionamide or isoniazid