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Ketamine and fMRI for Neuropathic Pain

Primary Purpose

Neuralgia

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

RS-fMRI

Ketamine

About this trial

This is an interventional diagnostic trial for Neuralgia focused on measuring Ketamine, fMRI, refractory neuropathic pain

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Toronto Western Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RS-fMRI

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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'

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

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

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

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

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

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

Change in quality of life at 1 month post-infusion, as measured by Short Form-36 (SF-36) v2 Health Survey

Change in quality of life at 3 months post-infusion, as measured by Short Form-36 (SF-36) v2 Health Survey

Full Information

NCT ID

NCT02373449

First Posted

February 9, 2015

Last Updated

April 26, 2021

Sponsor

University Health Network, Toronto

1. Study Identification

Unique Protocol Identification Number

NCT02373449

Brief Title

Ketamine and fMRI for Neuropathic Pain

Official Title

Functional Magnetic Resonance Imaging to Predict and Correlate Clinical Outcomes of Ketamine Infusions for Refractory Neuropathic Pain

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

February 2015 (undefined)

Primary Completion Date

December 2019 (Actual)

Study Completion Date

December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Health Network, Toronto

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed Description

This trial is exploratory, prospective, non-randomized, single cohort, single-center, with no blinding of participants, treating physicians, and investigators. Study participants undergo a resting-state fMRI before, after and at '1-month post-ketamine infusion' (standard care). Patients will be recruited over 2 years, from Pain Clinics at Toronto Western Hospital and Mount Sinai Hospital. The primary null hypothesis for this trial is that there are no fMRI brain patterns of patients with neuropathic pain that predict pain relief following ketamine infusion. The secondary null hypothesis for this trial is that there are no correlations between specific fMRI brain patterns of patients with neuropathic pain and change in intensity of pain immediately following ketamine infusion. Further secondary hypothesis include that cortical reorganization in the brain as measured by fMRI at one month after the infusion of ketamine does not correlate with persisting analgesic benefit in patients with neuropathic pain. Finally, we hypothesize that ketamine infusions do not provide significant pain relief, reduction in anxiety and depression, and improvement in quality of life early (at 1 month) and late (at 3 months) after the infusions in patients with neuropathic pain.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuralgia

Keywords

Ketamine, fMRI, refractory neuropathic pain

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RS-fMRI

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

RS-fMRI

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ketamine

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Time Frame

1 month following ketamine infusion

Secondary Outcome Measure Information:

Title

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'

Time Frame

3 months following ketamine infusion

Title

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

Time Frame

1 month following ketamine infusion

Title

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

Time Frame

3 months following ketamine infusion

Title

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

Time Frame

1 month following ketamine infusion

Title

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

Time Frame

3 months following ketamine infusion

Title

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

Time Frame

1 month following ketamine infusion

Title

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

Time Frame

3 months following ketamine infusion

Title

Change in quality of life at 1 month post-infusion, as measured by Short Form-36 (SF-36) v2 Health Survey

Time Frame

1 month following ketamine infusion

Title

Change in quality of life at 3 months post-infusion, as measured by Short Form-36 (SF-36) v2 Health Survey

Time Frame

3 month following ketamine infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anuj Bhatia

Organizational Affiliation

UHN

Official's Role

Principal Investigator

Facility Information:

Facility Name

Toronto Western Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T2S8

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

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