D-Cycloserine for Fibromyalgia

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
University of Calgary, Calgary, Canada
Fibromyalgia+1 More
D-Cycloserine - Drug
Eligibility
18+
All Sexes
What conditions do you have?
Select

Study 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-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. 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.

Eligible Conditions

  • Fibromyalgia

Treatment Effectiveness

Effectiveness Progress

1 of 3

Study Objectives

6 Primary · 52 Secondary · Reporting Duration: Administered at baseline, halfway (week 2), after rTMS treatment (week 4), and at one month follow up (week 8)

Week 8
Change in Anxiety as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Central Sensitization Pain as measured by the The Central Sensitization Inventory (CSI)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Choice Reaction Time
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Digit Symbol Substitution
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Perceived Deficits Questionnaire - 5 item scale (PDQ-5)
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Trail Making Test part B
Change in Cognitive Function - THINC-integrated tool (THINC-it)- Working Memory
Change in Cognitive Function - THINC-it- Choice Reaction Time
Change in Cognitive Function - THINC-it- Digit Symbol Substitution
Change in Cognitive Function - THINC-it- PDQ-5
Change in Cognitive Function - THINC-it- Trail Making Test part B
Change in Cognitive Function - THINC-it- Working Memory
Change in Depression as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Fatigue as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Pain Intensity as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Pain Interference as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Physical Function as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Sleep Disturbances as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in Social Function as measured by the Patient Reported Outcomes Measurement Information System (PROMIS-29)
Change in fatigue symptoms as measured by the Chalder Fatigue Questionnaire
Change in fibromyalgia severity as measured by the Polysymptomatic Distress Scale (PDS).
Change in quality of Life as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire
Change in self reported cognitive failures as measured by The Cognitive Failures Questionnaire (CFQ)
Change in self reported cognitive function as measured by The Multidimensional Inventory of Subjective Cognitive Impairment (MISCI)
Change in self-reported pain as measured by the Short-Form McGill Pain Questionnaire (SF-MPQ)
Change in self-reported pain as measured by the painDETECT scale.
Change in self-reported personality traits as measured by the Big Five Inventory (BFI)
Changes in catastrophic thinking related to pain using the Pain Catastrophizing Questionnaire (PCQ)
Changes in general health as measured by a visual analog scale (VAS)
Changes in self-reported anxiety as measured by the Generalized Anxiety Disorder (GAD-7) questionnaire
Changes in self-reported depression and anxiety as measured by the The Hospital Anxiety and Depression Scale (HADS)
Changes in self-reported depression as measured by the Quick Inventory of Depressive Symptoms (QIDS-SR)
Changes in sleep quality as measured by the The Insomnia Severity Index (ISI)
Implicit Suicidality
Week 8
Revised Fibromyalgia Impact Questionnaire (FIQR)
Sustained changes in Revised Fibromyalgia Impact Questionnaire (FIQR)
Week 8
Clinical Global Impression- Improvement
Clinical Global Impression- Severity
Higher rates of clinical depression remission
Higher rates of clinical depression response
Montgomery-Asberg Depression Rating Scale (MADRS)
Number of participants with clinical depression remission
Number of participants with clinical depression response
Week 4
Differential change in the will be mediated by fidelity to the protocol
Differential improvement in the will be mediated by fidelity to the protocol
Week 4
Incidence of Treatment-Emergent Adverse Events
Week 8
Changes in pain medication usage
MRI scan will be completed at baseline
Fibro vs Healthy Control Magnetic Resonance (MR) spectroscopy
Fibro vs Healthy Control functional Magnetic Resonance Imaging
Neuromelanin
Week 4
Change in Magnetic Resonance (MR) spectroscopy
Change in functional Magnetic Resonance Imaging
Week 4
Changes in inflammatory markers
Week 4
Quantitative Sensory Testing (QST) - Central sensitization via Temporal summation
Quantitative Sensory Testing (QST) - Conditioned pain modulation via cold-pressor conditioning
Quantitative Sensory Testing (QST) - Pain pressure thresholds via Algometry
Quantitative Sensory Testing (QST) - cold-pressor tolerance testing
Single timepoint. First day of TMS treatment, 90 minutes after ingestion of blinded oral capsule.
Differential change in the will be mediated by D-Cycloserine plasma level
Differential improvement in the will be mediated by D-Cycloserine plasma level
Week 8
Side Effects

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Trial Design

2 Treatment Groups

D-Cycloserine
1 of 2
Placebo
1 of 2
Experimental Treatment
Non-Treatment Group

90 Total Participants · 2 Treatment Groups

Primary Treatment: D-Cycloserine · Has Placebo Group · Phase 2

D-CycloserineExperimental Group · 2 Interventions: D-Cycloserine, iTBS repetitive Transcranial Magnetic Stimulation (rTMS) · Intervention Types: Drug, Device
PlaceboPlaceboComparator Group · 2 Interventions: Placebo oral tablet, iTBS repetitive Transcranial Magnetic Stimulation (rTMS) · Intervention Types: Drug, Device
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
D-Cycloserine
2011
Completed Phase 4
~1870

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: administered at baseline, halfway (week 2), after rtms treatment (week 4), and at one month follow up (week 8)
Closest Location: University of Calgary · Calgary, Canada
Photo of Calgary 1Photo of Calgary 2Photo of Calgary 3
2004First Recorded Clinical Trial
1 TrialsResearching Fibromyalgia
271 CompletedClinical Trials

Who is running the clinical trial?

University of CalgaryLead Sponsor
692 Previous Clinical Trials
449,739 Total Patients Enrolled
Alexander McGirr, MD, PhDPrincipal InvestigatorUniversity of Calgary
2 Previous Clinical Trials
101 Total Patients Enrolled

Eligibility Criteria

Age 18+ · All Participants · 9 Total Inclusion Criteria

Mark “yes” if the following statements are true for you:
You have a score of at least 41 on the FIQR.
You have a diagnosis of fibromyalgia as per the American College of Rheumatology 2016 fibromyalgia criteria.
You are competent to consent to treatment.
You have had no change in dose, or initiation of any psychotropic medication in the 4 weeks prior to randomization.
You have passed the TMS adult safety screening (TASS) and MRI screening questionnaire.

About The Reviewer

Michael Gill preview

Michael Gill - B. Sc.

First Published: October 9th, 2021

Last Reviewed: August 12th, 2022

Michael Gill holds a Bachelors of Science in Integrated Science and Mathematics from McMaster University. During his degree he devoted considerable time modeling the pharmacodynamics of promising drug candidates. Since then, he has leveraged this knowledge of the investigational new drug ecosystem to help his father navigate clinical trials for multiple myeloma, an experience which prompted him to co-found Power Life Sciences: a company that helps patients access randomized controlled trials.