Safety and Efficacy of Ketamine Intravenous Infusions in the Treatment of Fibromyalgia

A Two-part Study to Access the Safety and Efficacy of Ketamine Intravenous Infusions in the Treatment of Fibromyalgia

Previous studies of intravenous ketamine, which is a non-competitive N-methyl-D aspartate receptor antagonist, for fibromyalgia pain relief are limited to three studies. Two studies have focused on short-term pain relief of intravenous ketamine by measuring the patients' pain levels immediately before and after the infusion. Currently, existing studies used short-term infusions (30-40 minutes) of sub-anesthetic doses of ketamine for pain relief in fibromyalgia patients, whereas the Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists recommend infusing IV ketamine for at least two hours and a minimal total dose of 80 mg.

The rationale of this study is to expand on the existing data of safety and efficacy of intravenous ketamine to relieve fibromyalgia pain. Specifically, this investigation will add data to fill the existing gap regarding the short- and long-term pain relief in the treatment of fibromyalgia with intravenous ketamine infusions. The study will also attempt to determine safety and tolerability. In addition, the characteristics of treatment responders versus non-responders will be assessed in an effort to determine whether specific characteristics can be used to predict treatment response in this group of patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Intravenous Ketamine Infusions

Detailed Description

This study consists of two parts. The first part is a single-centre, retrospective chart review to analyze and summarize the investigators' experience with intravenous ketamine infusions in the treatment of patients with fibromyalgia who received at least four infusions for pain management. For the second part, patients who already received at least three intravenous ketamine infusions (for optimal dose determination) will be enrolled in an open single-group prospective study to receive one intravenous ketamine treatment. In this prospective study, the investigators will evaluate infusion effectiveness, safety, and tolerability as well as the influence of patients' demographic and medical characteristics, including depression status and ketamine dissociation symptoms, on the treatment outcome.

This two-part study aims to evaluate whether intravenous ketamine is effective in reducing pain in patients diagnosed with fibromyalgia. To achieve this goal, the study will assess the effect of intravenous ketamine infusions on short- and long-term pain relief. The study will also evaluate the safety and tolerability of ketamine infusions in fibromyalgia patients and factors that may have an impact on the treatment outcome.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Thornhill, Ontario, Canada, L4J 1W3
      • Wilderman Medical Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from Wilderman Medical Clinic, a chronic pain clinic located in Thornhill, Ontario. The clinic consists of state-of-the-art out-patient facilities, an interdisciplinary team and nursing support.

Description

Inclusion criteria:

To be included in Part 1 of the study, patients must fulfil the following criteria:

• Given written consent to permit Wilderman Medical Clinic investigators to use their medical and demographic information in research studies.
• Male or female >18 years of age
• Having been diagnosed with fibromyalgia
• Received at least 4 IV ketamine infusion(s)
• Made at least one rating of pain (NRS) immediately before the intervention and one after the intervention
• Had follow-up data recorded on the follow-up visit: percentage and duration of pain relief

To be included in Part 2 of the study, patients must fulfil the following criteria:

• Male or female >18 years of age
• Given the written Informed Consent Form to participate in the study
• Having been diagnosed with fibromyalgia
• Having been prescribed IV ketamine infusions treatment
• Passed safety screening for ketamine infusions
• Had at least 3 IV ketamine infusions for dose optimization
• Willingness and ability to comply with the study procedure and the ability to follow verbal and written instructions

Exclusion Criteria:

Patients will be excluded from Part 1 of the study if they meet any of the following criteria:

• Age less than 18 years old
• Absence of signed Informed Consent Form
• Patients who received less than 4 IV ketamine infusion(s)
• Insufficient information to conduct analysis (e.g. absence of pain ratings or follow up measurements)

Patients will be excluded from the Part II of the study if they meet any of the following criteria:

• Age less than 18 years old
• Absence of signed Informed Consent Form
• Received less than 3 IV ketamine infusions
• Have any contradictions to the administration of intravenous ketamine (known allergy to ketamine or fail to pass Ketamine treatment screening)
• Diagnosis of dementia or other cognitive impairments
• Any clinically significant acute or chronic medical condition that in the judgment of Investigator may preclude the use of intravenous ketamine or compromise patient safety, limit patient's ability to complete the study, and/or compromise the objectives of the study.
• Participation in any other clinical study within 3 months prior to screening and during the study period.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective Study Group; A total of approximately 30 patients diagnosed with fibromyalgia will be selected for participation in the study, all of whom will be treated with one IV ketamine infusion for pain relief according to their regular schedule of IV ketamine infusions. Each patient will be evaluated at baseline (prior to ketamine infusion), 40 minutes post-infusion, and at follow up visits.	Drug: Intravenous Ketamine Infusions; Ketamine will be slowly infused with the routine target dose 1.5-2 mg/kg over 3-4 hours.
Retrospective Study group; A total of approximately 20 patients will be selected for participation in the study, all of whom were treated with IV ketamine infusions. Information regarding clinically relevant outcomes will be obtained from chart reviews from patients who meet the eligibility criteria. The patient's response to treatment will be assessed.	Drug: Intravenous Ketamine Infusions; Ketamine will be slowly infused with the routine target dose 1.5-2 mg/kg over 3-4 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale (NRS)	The NRS is a standardized, one-dimensional measure of pain intensity. The pain intensity is rated by the participant using a scale from 0-10; 0 being the least (no pain) to 10 (worst pain imaginable).	Baseline visit: immediately before IV ketamine infusion
Numeric Rating Scale (NRS)	The NRS is a standardized, one-dimensional measure of pain intensity. The pain intensity is rated by the participant using a scale from 0-10; 0 being the least (no pain) to 10 (worst pain imaginable).	Baseline visit: immediately after the IV ketamine infusion
Numeric Rating Scale (NRS)	The NRS is a standardized, one-dimensional measure of pain intensity. The pain intensity is rated by the participant using a scale from 0-10; 0 being the least (no pain) to 10 (worst pain imaginable).	Follow-up visits at 1, 2, 3, and 4 weeks after the IV ketamine infusion
Integral of pain relief	IPR is a multidimensional measure combining the duration of patients' pain relief (in days) and the percentage of pain relief that they had experienced. IPR seeks to tap into a fuller picture of the patients' pain relief, since it not only measures current pain levels, but patients' experience of pain, both in duration and percentage of relief, over a longer period of time. The scale has no restrictions, beginning at 0 (no treatment effect). Therefore, the higher the IPR value, the more effective the treatment was at reducing pain	Follow-up visits at 1, 2, 3, and 4 weeks after the IV ketamine infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Clinician-Administered Dissociative States Scale (CADSS)	The CADSS is a 27-item scale with 19 subject-rated items and 8 items scored by an observer. The subjective component consists of 19 items which are administered by a clinician who begins each question with the phrase "at this time" and then reads the item to the subject. The subject then endorses one of a range of possible responses: 0 = not at all, 1 = slightly, 2 = moderately, 3 = considerably, 4 = extremely. The subject's response on these 0 to 4 scales is recorded and the clinician moves on to the next item. Three non-empirically derived subscales for the CADSS have been proposed: amnesia (two items), depersonalization (five items), and derealization (12 items).	Baseline visit: immediately before IV ketamine infusion
The Clinician-Administered Dissociative States Scale (CADSS)	The CADSS is a 27-item scale with 19 subject-rated items and 8 items scored by an observer. The subjective component consists of 19 items which are administered by a clinician who begins each question with the phrase "at this time" and then reads the item to the subject. The subject then endorses one of a range of possible responses: 0 = not at all, 1 = slightly, 2 = moderately, 3 = considerably, 4 = extremely. The subject's response on these 0 to 4 scales is recorded and the clinician moves on to the next item. Three non-empirically derived subscales for the CADSS have been proposed: amnesia (two items), depersonalization (five items), and derealization (12 items).	Baseline visit: 40 minutes after the IV ketamine infusion
Patient Health Questionnaire (PHQ-9)	PHQ-9 is endorsed by the National Institute for Health and Clinical Excellence for use in primary care in measuring baseline depression severity and responsiveness to treatment. The 9 items on the PHQ-9 consist of the 9 criteria on which the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) depressive disorder diagnoses are based. A 4-point scale indicates a degree of severity; items are rated from 0 (not at all) to 3 (nearly every day).	Baseline visit: before IV ketamine infusion
Patient Health Questionnaire (PHQ-9)	PHQ-9 is endorsed by the National Institute for Health and Clinical Excellence for use in primary care in measuring baseline depression severity and responsiveness to treatment. The 9 items on the PHQ-9 consist of the 9 criteria on which the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) depressive disorder diagnoses are based. A 4-point scale indicates a degree of severity; items are rated from 0 (not at all) to 3 (nearly every day).	Follow-up visits at 1, 2, 3, and 4 weeks after the IV ketamine infusion
Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS)	The LANSS is a simple and valid 7-item tool for identifying patients whose pain is dominated by neuropathic mechanisms. Each item is a binary response (yes or no) to the presence of symptoms (5 items) or clinical signs (2 items). S-LANSS is a modified version of the LANSS pain scale to make it capable of self-completion.	Baseline visit: before IV ketamine infusion
Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS)	The LANSS is a simple and valid 7-item tool for identifying patients whose pain is dominated by neuropathic mechanisms. Each item is a binary response (yes or no) to the presence of symptoms (5 items) or clinical signs (2 items). S-LANSS is a modified version of the LANSS pain scale to make it capable of self-completion.	Follow-up visits at 1, 2, 3, and 4 weeks after the IV ketamine infusion
Fibromyalgia Impact Questionnaire, Revised (FIQR)	The Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia patients. The revised FIQ has 21 individual questions. All questions are based on an 11-point numeric rating scale of 0 to 10, with 10 being 'worst'. All questions are framed in the context of the past 7 days. The FIQR is divided into three linked sets of domains: (a) 'function' (contains 9 questions), (b) 'overall impact' (contains 2 questions), and (c) 'symptoms' (contains 10 questions). The FIQR is an updated version of the FIQ that has good psychometric properties, can be completed in less than 2 minutes and is easy to score.	Baseline visit: before IV ketamine infusion
Fibromyalgia Impact Questionnaire, Revised (FIQR)	The Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia patients. The revised FIQ has 21 individual questions. All questions are based on an 11-point numeric rating scale of 0 to 10, with 10 being 'worst'. All questions are framed in the context of the past 7 days. The FIQR is divided into three linked sets of domains: (a) 'function' (contains 9 questions), (b) 'overall impact' (contains 2 questions), and (c) 'symptoms' (contains 10 questions). The FIQR is an updated version of the FIQ that has good psychometric properties, can be completed in less than 2 minutes and is easy to score.	Follow-up visits at 1, 2, 3, and 4 weeks after the IV ketamine infusion
Patients Global Impression of Change (PGIC)	PGIC is a seven-point single-item scale ranging from 'very much worse' to 'very much improved' worse' with 'no change' as the mid-point that evaluates improvement with treatment during a clinical trial.	Follow-up visits at 1, 2, 3, and 4 weeks after the IV ketamine infusion
Periprocedural adverse effects	Variations of heart rate (beats per minute)	Baseline visit: During the infusion
Periprocedural adverse effects	Variations of blood pressure (mmHg)	Baseline visit: During the infusion
Periprocedural adverse effects	Variations of pulse oxygen saturation (percentage of hemoglobin carrying oxygen)	Baseline visit: During the infusion
Periprocedural adverse effects	Presence of dizziness, nausea, chest pain, shortness of breast	Baseline visit: During the infusion
Postprocedural adverse effects	Variations of heart rate (beats per minute)	Baseline visit: During 60-90 minutes after the procedure
Postprocedural adverse effects	Variations of blood pressure (mmHg)	Baseline visit: During 60-90 minutes after the procedure
Postprocedural adverse effects	Variations of pulse oxygen saturation (percentage of hemoglobin carrying oxygen)	Baseline visit: During 60-90 minutes after the procedure
Postprocedural adverse effects	Presence of dizziness, nausea, chest pain, shortness of breast	Baseline visit: During 60-90 minutes after the procedure

Collaborators and Investigators

• Sponsor: Wilderman Medical Clinic
• Investigators: Principal Investigator: Igor Wilderman, MD, Wilderman Medical Clinic

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: March 31, 2025
• First Posted (Actual): April 8, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Depression; Chronic Pain; Fibromyalgia; Neuropathic Pain; Pain Relief; Intravenous Ketamine Infusions; Dissociative State
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics; Neurotransmitter Agents; Anesthetics, Intravenous; Anesthetics, General; Excitatory Amino Acid Agents; Anesthetics, Dissociative; Excitatory Amino Acid Antagonists; Ketamine
• Other Study ID Numbers: WMC003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be available according to reasonable demands.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No