Ketamine and fMRI for Neuropathic Pain

NCT02373449 | Completed

• 1 other identifier: 14-8706-AE
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Neuropathic or nerve injury related pain (NP), an extremely unpleasant condition that is difficult to treat, often has a severe, persistent, and unremitting course. Conventional treatments are often ineffective in relieving NP. Recently, the investigators have developed a cost-efficient regimen involving use of low dose infusions of ketamine for treating neuropathic pain in patients in whom oral medications have failed. We have observed excellent benefits in many of these patients. However, this treatment requires titration and monitoring during the infusion and currently it is not possible to predict which patients will benefit from this intervention. The investigators have shown that functional magnetic resonance imaging (fMRI) of the brain can be used as a tool to predict relief of pain and to assess the effect of treatment in some chronic pain conditions. This innovative project involves development of an fMRI-guided treatment with intravenous ketamine in patients with NP. This study aims to analyze patterns of changes in fMRI of the brain, before and after infusion of ketamine and to correlate the changes with pain intensity. The information from this study will help to deliver this therapy earlier to those patients who are most likely to benefit from ketamine.

Conditions

Neuralgia

Keywords

Ketamine; fMRI; refractory neuropathic pain

Outcome Measures

Primary Outcomes (1)

• Correlation between 'baseline (pre-infusion) fMRI patterns' and 'pain relief (>50% pain reduction, as per NRS or 'Numerical Rating Scale')'

  1 month following ketamine infusion

Secondary Outcomes (9)

• Correlation between 'specific fMRI brain patterns at 1-month post-infusion' and 'change in neuropathic pain intensity (as per NRS) at 3-month post-infusion'

  3 months following ketamine infusion

• Change in pain intensity at 1 month post-infusion, as measured by Brief Pain Inventory (BPI)

  1 month following ketamine infusion

• Change in pain intensity at 3 months post-infusion, as measured by Brief Pain Inventory (BPI)

  3 months following ketamine infusion

• Change in anxiety at 1 month post-infusion, as measured by Hospital Anxiety and Depression Scale (HADS)

  1 month following ketamine infusion

• Change in anxiety at 3 months post-infusion, as measured by Hospital Anxiety and Depression Scale (HADS)

  3 months following ketamine infusion

Study Arms (1)

RS-fMRI

EXPERIMENTAL

All subjects will be instructed to keep their eyes closed but to remain awake during the fMRI measurement. Resting State fMRI (RS-fMRI) will be performed within four weeks of planned infusion of ketamine, immediately after the end of infusion of ketamine on the fifth (last) day of infusion, and on the one month follow-up appointment after the infusion.

Other: RS-fMRI; Drug: Ketamine

Interventions

RS-fMRI OTHER

Resting State-functional Magnetic Resonance Imaging. Protocols involving BOLD (blood oxygen level-dependent) and non-BOLD techniques will be used.

RS-fMRI

Ketamine DRUG

Part of standard care. To be performed over five consecutive days (Monday to Friday) for six hours per day. A therapeutic range of 0.5 to 2.0 mg/kg/hour is targeted.

RS-fMRI

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Refractory neuropathic pain diagnosed by a \>3 score on DN4 (Douleur Neuropathique 4) questionnaire
• Average daily pain intensity should be moderate or severe, as indicated by a \>3 score on NRS (Numerical Rating Scale)
• Duration of neuropathic pain should be more than three months
• Participants should have tried at least three medications for neuropathic pain. Each of these medications should belong to a different pharmacological group: anticonvulsants (gabapentin, pregabalin), tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine), serotonin noradrenaline reuptake inhibitors (venlafaxine, duloxetine), tramadol, opioids, cannabinoids, methadone, topical lidocaine and capsaicin patches.

You may not qualify if:

• Ketamine or lidocaine intravenous infusion within the 6 months preceding enrollment into this trial
• Contraindications to ketamine (allergy, pregnancy, uncontrolled arterial hypertension, uncontrolled hyperthyroidism, severe ischemic heart disease or heart failure, severe liver or kidney disease, space occupying lesion in the brain or the spinal cord, uncontrolled epilepsy and glaucoma)
• Ongoing litigation issues related to the patient's pain that may affect reporting of pain and quality of life
• An unstable medical or psychiatric condition that makes it unsafe to use study medications
• Participants unable to comply with the study protocol (e.g. follow-up visits, filling forms for measuring anxiety, depression, and quality of life)
• Relative (claustrophobia) or absolute contraindications for MRI

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T2S8, Canada

Location

MeSH Terms

Conditions

Neuralgia

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Anuj Bhatia

  UHN

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Anesthesiologist

Study Record Dates

• First Submitted: February 9, 2015
• First Posted: February 27, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)